预约演示

更新于：2026-06-20

Cabergoline

卡麦角林

更新于：2026-06-20

概要

基本信息

药物类型

小分子化药

别名

(8R)-6-allyl-N-[3-(dimethylamino)propyl]-N-(ethylcarbamoyl)ergoline-8-carboxamide、(8β)-N-[3-(dimethylamino)propyl]-N-[(ethylamino)carbonyl]-6-(2-propenyl)-ergoline-8-carboxamide、1-((6-allylergolin-8β-yl)carbonyl)-1-(3-(dimethylamino)propyl)-3-ethylurea

+ [15]

靶点

D2 receptor

作用方式

激动剂

作用机制

D2 receptor激动剂(多巴胺D2受体激动剂)

治疗领域

神经系统疾病内分泌与代谢疾病皮肤和肌肉骨骼疾病+ [1]

在研适应症

非在研适应症

原研机构

在研机构

Pfizer Japan, Inc.Strides Pharma Global Pte Ltd.

+ [1]

非在研机构-

权益机构-

最高研发阶段批准上市

首次获批日期

澳大利亚 (1995-04-21),

高催乳素血症

最高研发阶段(中国)临床3期

特殊审评-

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结构/序列

分子式C26H37N5O2

InChIKeyKORNTPPJEAJQIU-KJXAQDMKSA-N

CAS号81409-90-7

关联

119

项与卡麦角林相关的临床试验

NCT06909123

/ Not yet recruiting临床2期IIT

A Reduced Dose of Cabergoline for Lactation Inhibition After Second-Trimester Abortion or Pregnancy Loss

Most patients seeking abortion care or management of pregnancy loss in the second trimester will lactate, which can be physically and emotionally painful. The efficacy of a one-time dose of cabergoline has been previously demonstrated to prevent breast symptoms for these patients. This study seeks to determine if investigators can more precisely manage these patients with a reduced dose appropriate for the physiology of the second trimester, thereby reducing the medication cost and reducing or eliminating the uncomfortable medication side effects.

开始日期2026-07-01

申办/合作机构

Stanford University

NCT07603466

/ Enrolling by invitation临床4期IIT

Combination Osilodrostat and Cabergoline Versus Osilodrostat Alone in Cushing's Disease in Iraq: Assessment of Efficacy and Safety

Cushing disease remains a challenging endocrine disorder in which persistent or recurrent hypercortisolism often requires medical therapy after surgery or when surgery is not feasible. Combination medical therapy has emerged as a rational strategy to improve biochemical control through complementary mechanisms while potentially reducing treatment escape and dose-related toxicity. Cabergoline exerts pituitary D2-receptor-mediated inhibition of ACTH secretion and may provide partial cortisol control in selected patients, although treatment escape and variable durability remain important limitations. Osilodrostat is a potent 11β-hydroxylase inhibitor that produces rapid and often substantial reductions in cortisol secretion, with clinical improvement in metabolic and cardiovascular features of hypercortisolism. The osilodrostat-cabergoline combination is mechanistically attractive because it pairs central ACTH suppression with peripheral blockade of cortisol synthesis, but published evidence remains limited to small real-world experiences and does not yet define optimal sequencing, dosing, or long-term benefit. Safety considerations include adrenal insufficiency from overtreatment, osilodrostat-associated hypertension from mineralocorticoid precursor accumulation, and hyperandrogenism due to steroid precursor shunting.
Combination medical therapy in Cushing disease is a promising individualized approach, and the osilodrostat-cabergoline pairing is biologically plausible and potentially effective, but current literature is insufficient to support firm recommendations regarding efficacy, safety, or patient selection.
The study aims to evaluate whether a combination can result in rapid, more control of Cushing's disease (clinically and biochemically)? Can cabergoline reduces Osilodrostat dose requirement, reduces Osilodrostat related mineralocorticoid and hyperandrogenism side effects?

开始日期2026-05-11

申办/合作机构

University Of Basrah

NCT07386080

/ Not yet recruiting临床4期IIT

The Safety of Carbergoline Versus Placebo for Antipsychotic Induced Hyperprolactinemia: A Pragmatic, Randomised, Non-inferiority Trial With Blinded Outcome.

The goal of this clinical trial is to learn if cabergoline is safe to use in patients with antipsychotic-induced hyperprolactinemia in adults with scizophrenia. The main question it aims to answer :
Is the severity of positive and negative symptoms affected by the use of cabergoline?
Researchers will compare cabergolin to placebo to see if positive and negative symptoms are equel in both groups.
Participants will, in a blinded manor, take either placebo tablets or cabergoline for 12 weeks. The severity of positive and negative symptoms will be evaluated before and after the intervention in both groups.

开始日期2026-05-01

申办/合作机构

Zealand University Hospital

[+1]

100 项与卡麦角林相关的临床结果

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100 项与卡麦角林相关的转化医学

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100 项与卡麦角林相关的专利（医药）

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2,036

项与卡麦角林相关的文献（医药）

2026-12-31·Journal of Maternal-Fetal & Neonatal Medicine

Aortic dissection during the perinatal period in women with Marfan-related disorders: a retrospective cohort study using the Japanese Diagnosis Procedure Combination database

Article

作者: Wada-Hiraike, Osamu ; Yasunaga, Hideo ; Matsuo, Yuichiro ; Nariai, Maika ; Iriyama, Takayuki ; Hirota, Yasushi ; Sayama, Seisuke ; Sasabuchi, Yusuke ; Harada, Miyuki

OBJECTIVE:

Women with Marfan-related disorders face an elevated risk of aortic dissection during pregnancy and the postpartum period. This study aimed to investigate the incidence of aortic dissection during the perinatal period in women with Marfan-related disorders.

METHODS:

This retrospective cohort study analyzed data extracted from the Japanese Diagnosis Procedure Combination, a nationwide administrative claims database. We included women diagnosed with Marfan-related disorders (Marfan syndrome, Loeys-Dietz syndrome, or Ehlers-Danlos syndrome) who delivered between 2010 and 2023. We assessed the incidence of aortic dissection during pregnancy or postpartum hospitalization, and the incidence of re-hospitalization for aortic dissection. Moreover, we described the use of cabergoline and the incidence of aortic dissection.

RESULTS:

During the study period, we identified a total of 226 deliveries by 175 women with Marfan-related disorders. Cesarean section accounted for 69.0% of deliveries. During pregnancy, 1.8% of cases (4/226) experienced aortic dissection and required aortic surgery. In the postpartum period, 2.7% of cases (6/226) experienced aortic dissection during postpartum hospitalization. Within 1 year after delivery, 2.7% of cases (6/226) underwent re-hospitalization for aortic dissection. Cabergoline was administered for elective avoidance of breastfeeding within 2 days postpartum in 15 (6.6%) cases. The incidence of postpartum aortic dissection did not differ significantly between cabergoline users and non-users.

CONCLUSIONS:

Women with Marfan-related disorders may remain at risk of developing aortic dissection for up to 1 year postpartum.

2026-07-01·TRENDS IN CARDIOVASCULAR MEDICINE

Parkinson’s disease & cardiovascular disease: A narrative review

Review

作者: Arauz, Antonio ; Malik, Shaun ; Meghdadi, Amin ; Gupta, Shyla ; Baranchuk, Adrian ; Ibrahim, Alexander ; Baratta, Sergio Juan ; Duli, Ergi ; Langleben, Nicole ; Yacob, Souzan

Parkinson's disease (PD) is a synucleinopathy best known for its motor symptoms, but emerging research shows it also impacts the cardiovascular system. In this paper, we explore the association between PD and cardiovascular disease (CVD), reviewing six key categories: cardiac dysautonomia, coronary artery disease, arrhythmias, cardiomyopathy, heart valve disease, and heart failure. We also discuss risk factors, epidemiology, and overlapping pathophysiology. Cardiac dysautonomia is the most frequently reported cardiovascular issue in PD and includes orthostatic hypotension, postprandial hypotension, supine hypertension, and nocturnal non-dipping blood pressure. PD also appears to be positively associated with coronary artery disease. Early-stage PD is linked to atrial fibrillation, but overall, there is no consistent increase in arrhythmias outside of certain PD medications. Structural and functional cardiac changes such as left ventricular hypertrophy and diastolic dysfunction have also been reported in PD, which may predispose to heart failure and cardiomyopathy. Dopamine agonists pergolide and cabergoline are associated with valve regurgitation, but this seems to be drug-related rather than caused by PD. Shared risk factors like aging, male sex, diabetes, and inflammation help explain the PD-CVD connection. However, some CVD risk factors like high LDL and smoking are associated with lower PD risk. Autonomic dysfunction, impaired lipid and glucose metabolism, and chronic inflammation may all contribute to disease overlap. Our review consolidates existing research to highlight the importance of recognizing cardiovascular manifestations in PD, which may present before motor symptoms. This has important implications for earlier diagnosis, better screening, and more effective management of PD.

2026-06-01·Pituitary

Impulse control disorders and their relationship with psychopathology in patients treated with cabergoline for hyperprolactinaemia

Article

作者: Verrienti, Martina ; Ambrosio, Maria Rosaria ; Valier, Beatrice ; Giampietro, Antonella ; Cristilli, Giulia ; Zerbinati, Luigi ; Zatelli, Maria Chiara ; Okai, David ; Braccia, Francesca ; Grassi, Luigi ; Toffanin, Tommaso

Abstract:

Purpose:

Dopamine agonists (DAs), such as cabergoline (CAB), are first-line treatments for hyperprolactinaemia but have been associated with impulse control disorders (ICD). This observational study aimed to investigate the prevalence, severity, and clinical characteristics of ICD in CAB-treated patients compared with controls, using a combined clinician-administered and multimethod self-report assessment.

Methods:

A total of 126 participants were included: 63 patients with prolactin-secreting pituitary adenomas receiving cabergoline (CAB) and 63 controls (CG). ICD were evaluated using the Parkinson’s Impulse Control Scale (PICS) as the reference diagnostic measure, alongside self-report questionnaires assessing ICD-related behaviors. Psychiatric comorbidity was assessed using the Mini International Neuropsychiatric Interview (MINI), and general psychopathology using the Brief Symptom Inventory-53 (BSI-53).

Results:

ICD were identified in 15.9% of CAB-treated patients and 6.3% of controls, indicating a more than twofold higher prevalence and greater severity in the CAB group, although differences were not statistically significant. When restricted to CAB-related cases, prevalence decreased to 12.7%. The Questionnaire for Impulsive-Compulsive Disorders (QUIP) showed moderate sensitivity (71.4%) but low positive predictive value (41.7%). Within the CAB group, ICD-positive patients had shorter treatment duration and lower weekly doses. No significant differences emerged in MINI or BSI-53 results, although psychiatric comorbidity was present in ~ 50% of ICD cases.

Conclusion:

CAB therapy was associated with a modest but clinically meaningful increase in ICD. Screening tools may support early identification, but positive findings require confirmation through comprehensive clinical assessment.

项与卡麦角林相关的新闻（医药）

2026-06-15

·BioSpace

Crinetics Presents Long Term Data at ENDO 2026 Confirming PALSONIFY™ (paltusotine) Provides Durable, Consistent Acromegaly Control

Data from up to two years of treatment in PATHFNDR-1 and PATHFNDR-2 open-label extension studies show PALSONIFY maintained lower IGF-1 levels and stable symptoms Treatment also resulted in stable or reduced pituitary tumor volumes for up to 48 weeks Additional ENDO highlights include long-term ACROBAT data demonstrating PALSONIFY and cabergoline combination improves biochemical control of acromegaly SAN DIEGO, June 14, 2026 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) today announced new long-term data from its clinical development program evaluating novel PALSONIFY TM (paltusotine) in acromegaly during an oral presentation at the Endocrine Society’s Annual Meeting, ENDO 2026. Notably, pooled data from the open-label extension (OLE) trials of PATHFNDR-1 and PATHFNDR-2 show that after two years of treatment, PALSONIFY was effective and well-tolerated in patients who were switched from standard-of-care monthly injectable somatostatin receptor ligands (SRLs) and those who were medically untreated, respectively, when oral, once-daily PALSONIFY was initiated. “To assess acromegaly disease control while on medication, endocrinologists carefully monitor control of IGF-1 levels, control of acromegaly symptoms, and stabilization of pituitary tumors,” said Dr. Alan Krasner, M.D., Chief Endocrinologist, Crinetics. “At this year’s ENDO meeting, long-term safety and efficacy data from the PATHFNDR OLE trials will be presented. These studies indicate that Palsonify is well tolerated and maintains control of all three aspects of disease control with long-term follow-up. Since its launch late last year, we are learning that Palsonify is already making a meaningful difference in the lives of many people with acromegaly, and we hope these data will be helpful for patients and for their health care providers.” Pooled OLE Efficacy and Safety Results PATHFNDR-1 Data The PATHFNDR-1 Phase 3 trial enrolled adults with acromegaly who were biochemically controlled on monthly injectable SRLs. Following a 36-week randomized, placebo-controlled period, 53 of 57 participants (93%) entered the ongoing single-arm open-label extension (OLE) trial. Baseline mean IGF-1 levels for OLE participants (n=53) was 0.91x Upper Limit of Normal (ULN). These levels remained stable at both 48 weeks (n=50) and 96 weeks (n=47) of the study: 0.82x ULN and 0.81, respectively. Symptoms associated with acromegaly, as measured by the Acromegaly Symptom Diary (ASD), remained stable from baseline at assessed timepoints. Additionally, pituitary tumor volumes were reported as stable in all patients at week 48, relative to OLE baseline. PATHFNDR-2 Data The PATHFNDR-2 trial evaluated once-daily oral PALSONIFY in adults with biochemically uncontrolled acromegaly (baseline IGF-1 > 1.3 × ULN). After a 24-week randomized controlled (RC period, 103 of 106 completers (97.2%) entered the ongoing OLE, along with 11 additional patients who were eligible for the RC phase but enrolled directly into the OLE. Baseline mean IGF-1 levels for OLE participants (n=114) was 1.64×ULN. These levels decreased from baseline at both 48 weeks (n=98) and 72 weeks (n=78) of the study: 1.06×ULN and 0.96×ULN, respectively. Relative to OLE baseline, pituitary tumor volume was reduced by >20% in 7 of 83 PATHFNDR-2 patients with available MRI scans at OLE Week 24. Tumor volume was reported as stable in the other 76 participants. In both OLEs, median ASD scores were stable at the timepoints assessed. Symptoms associated with acromegaly, as measured by the Acromegaly Symptom Diary (ASD), remained stable from baseline at assessed timepoints. No new safety signals were found. In the pooled OLE population (n=167), the most common adverse events (incidence>10%) were diarrhea (15.6%), arthralgia (11.4%), headache (11.4%), and urinary tract infection (10.2%). Four patients (2.4%) discontinued from an OLE due to adverse events as of this analysis. These results were included in an oral presentation at ENDO 2026 titled “Efficacy and Safety of Once-Daily Oral Paltusotine in Patients with Acromegaly: Up to 2 Years in the PATHFNDR-1 and PATHFNDR-2 Open-Label Extension Studies.” Additionally, an analysis was presented at ENDO 2026 that evaluated the safety and efficacy of PALSONIFY in combination with oral cabergoline in patients with acromegaly who have been followed for up to four years in ACROBAT Advance, an ongoing, single-arm, open-label extension phase 2 study. IGF-I levels on paltusotine monotherapy were similar to parent study baseline values (on injected SRL), but for those in whom IGF-1 had not yet normalized, it further improved when oral cabergoline was added. Combination therapy was well tolerated. Crinetics’ ENDO 2026 presentations can be found at: PALSONIFY™ (paltusotine) INDICATION: PALSONIFY is a somatostatin receptor agonist indicated for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS: Cholelithiasis and Its Complications: Cholelithiasis, including related complications such as acute cholecystitis and pancreatitis, have been reported. Monitor patients periodically. Discontinue PALSONIFY if complications of cholelithiasis occur and treat appropriately. Hyperglycemia and Hypoglycemia: Hyperglycemia, diabetes mellitus, or hypoglycemia, may occur. Monitor blood glucose levels when PALSONIFY treatment is initiated or when dosage is altered. Adjust antidiabetic treatment accordingly. Cardiovascular Abnormalities: Cardiac conduction abnormalities and other ECG changes such as PR interval prolongation, bradycardia, sinus arrest, and atrioventricular block may occur in patients with acromegaly and were reported in PALSONIFY clinical trials. Dosage adjustments of concomitant drugs that have bradycardic effects may be necessary. Thyroid Function Abnormalities: Somatostatin analogs may suppress the secretion of thyroid-stimulating hormone, which may result in hypothyroidism. Periodic assessment of thyroid function is recommended. Steatorrhea and Malabsorption of Dietary Fats: Somatostatin analog treatment may result in malabsorption of dietary fats and subsequent symptoms of steatorrhea, loose stools, abdominal bloating, and weight loss. If new or worsening symptoms are reported with PALSONIFY, evaluate patients for potential pancreatic exocrine insufficiency and manage accordingly. Vitamin B12 Deficiency: Vitamin B12 deficiency may occur. Monitor vitamin B12 levels, if clinically indicated. ADVERSE REACTIONS: Most common adverse reactions (>5%) are diarrhea, abdominal pain, nausea, decreased appetite, sinus bradycardia, hyperglycemia, palpitations, and gastroenteritis. DRUG INTERACTIONS: Strong or Moderate CYP3A4 Inducers: may decrease PALSONIFY exposure. May require an increased dosage of PALSONIFY. Proton Pump Inhibitors: may decrease PALSONIFY exposure. May require an increased dosage of PALSONIFY. Avoid concomitant use of proton pump inhibitors in patients who are already on PALSONIFY 60 mg. Cyclosporine: may decrease cyclosporine exposure. May require cyclosporine dosage adjustment when used with PALSONIFY; follow therapeutic monitoring recommendations. Please report adverse events to Crinetics Pharmaceuticals at 1-833-CRN-INFO (1-833-276-4636) or FDA at 1-800-FDA-1088 or . ww.fda.gov/medwatch . Please see Full Prescribing Information including Patient Information . About PALSONIFY™ ( Paltusotine) PALSONIFY, a selectively-targeted somatostatin receptor type 2 (SST2) nonpeptide agonist, is the first and only once-daily, oral therapy approved for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. In Phase 3 studies, once-daily, oral PALSONIFY maintained IGF-1 levels and symptom control in patients with acromegaly who were switched from monthly injectable medications (PATHFNDR-1) and rapidly decreased IGF-1 levels and symptom burden in medically untreated acromegaly patients (PATHFNDR-2). IGF-1 is the primary biomarker endocrinologists use to manage acromegaly patients. Paltusotine is also in Phase 3 clinical development for carcinoid syndrome associated with neuroendocrine tumors (CAREFNDR). Results from a Phase 2 study in carcinoid syndrome demonstrated rapid and sustained reductions in flushing episodes and bowel movement frequency, which are the most common symptoms of carcinoid syndrome. PALSONIFY is approved in the U.S. for the first-line treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. It is also approved for use in the EU for the medical treatment of adult patients with acromegaly. About Crinetics Pharmaceuticals Crinetics Pharmaceuticals is a global pharmaceutical company committed to transforming the treatment of endocrine diseases and endocrine-related tumors through science rooted in patient needs. Crinetics is focused on discovering, developing, and commercializing novel therapies, with a core expertise in targeting G-protein coupled receptors (GPCRs) with small molecules that have specifically tailored pharmacology and properties. Crinetics’ first commercial product, PALSONIFY™ (paltusotine), is the first once-daily, oral treatment approved by the U.S. FDA and EMA for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. Paltusotine is also in clinical development for carcinoid syndrome associated with neuroendocrine tumors. Crinetics’ deep pipeline of 10+ disclosed programs includes late-stage investigational candidate atumelnant, which is currently in development for congenital adrenal hyperplasia and ACTH-dependent Cushing’s syndrome, and CRN09682, a nonpeptide drug conjugate candidate that is being developed to treat somatostatin receptor 2 (SST2) expressing neuroendocrine tumors and other SST2 expressing solid tumors. Additional discovery programs are focused on a variety of endocrine targets such as thyroid stimulating hormone (TSH), parathyroid hormone (PTH), somatostatin receptor 3 (SST3), growth hormone (GH), glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP), as well as GPCR-targeted oncology indications. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward-looking statements, including statements regarding the plans and timelines for the clinical development of atumelnant for congenital adrenal hyperplasia and ACTH-dependent Cushing’s syndrome and PALSONIFY for carcinoid syndrome , including the therapeutic potential and clinical benefits or safety pro and the therapeutic potential for our development candidates. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential,” “upcoming” or “continue” or the negative of these terms or other similar expressions. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, including, without limitation, initial or topline data that we report may change following completion or a more comprehensive review of the data related to the clinical studies and such data may not accurately reflect the complete results of a clinical study, and the FDA and other regulatory authorities may not agree with our interpretation of such results; geopolitical events may disrupt Crinetics’ business and that of the third parties on which it depends, including delaying or otherwise disrupting its clinical studies and preclinical studies, manufacturing and supply chain, or impairing employee productivity; the success of Crinetics’ clinical studies and nonclinical studies; regulatory developments in the United States and foreign countries; clinical studies and preclinical studies may not proceed at the time or in the manner expected, or at all; the timing and outcome of research, development and regulatory review is uncertain, and Crinetics’ drug candidates may not advance in development or be approved for marketing; and the other risks and uncertainties described in the Company’s periodic filings with the Securities and Exchange Commission (SEC). The events and circumstances reflected in the company’s forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Additional information on risks facing Crinetics can be found under the heading “Risk Factors” in Crinetics’ periodic filings with the SEC, including its annual report on Form 10-K for the year ended December 31, 2025 and quarterly report on Form 10-Q for the quarter ended March 31, 2026. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Except as required by applicable law, Crinetics does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Contact: Media:  Natalie Badillo  Head of Corporate Communications  nbadillo@crinetics.com (858) 345-6075   Investors: Gayathri Diwakar Head of Investor Relations gdiwakar@crinetics.com (858) 345-6340

2026-06-12

·中华内分泌代谢杂志

【内分泌代谢论坛】垂体特异性转录因子1谱系垂体神经内分泌肿瘤创新靶点及药物发现

点击标题下「蓝色微信名」可快速关注文章来源：中华内分泌代谢杂志, 2026,42(03)：182-187.DOI:10.3760/cma.j.cn311282-20251105-00540 作者：张柏仟吴哲褒薛礼摘要垂体神经内分泌肿瘤(pituitary neuroendocrine tumor, PitNET)是常见的颅内肿瘤，其中垂体特异性转录因子1(pituitary-specific positive transcription factor 1, PIT1)谱系是临床最常见的功能性亚型，因占位效应和激素过度分泌严重危害患者生活质量。尽管临床药物多巴胺激动剂和生长抑素类似物被广泛应用，适应证局限与耐药仍是药物治疗PitNET的痛点。本文聚焦PIT1谱系肿瘤，系统梳理了其异常增殖与激素分泌失衡的分子机制及创新药物靶点开发进展，并讨论了从单通路阻断向多靶点联合治疗策略转变的可行性。虽然多数研究尚处于临床前阶段，但相关机制的解析为PIT1谱系肿瘤的创新药物研发以实现精准分子干预提供了重要的理论依据与转化方向。垂体神经内分泌肿瘤(pituitary neuroendocrine tumor, PitNET)起源于垂体前叶上皮细胞，其中具有临床表现的PitNET患病率约为1/1 100 [ 1 ]。2022年世界卫生组织(World Health Organization, WHO)基于关键转录因子将PitNET分为垂体特异性转录因子1(pituitary-specific positive transcription factor 1, PIT1)、T-box垂体转录因子(T-box pituitary transcription factor, TPIT)、类固醇生成因子1(steroidogenic factor 1, SF1)及无明确来源四大谱系。PIT1谱系主要包括催乳素瘤(prolactinoma)、生长激素瘤(somatotropinoma)与促甲状腺激素瘤(thyroid-stimulating hormone-secreting adenoma)，是功能性腺瘤中占比最高的亚型 [ 1 , 2 ]。其危害性在于：一方面，由于肿瘤增生可压迫、侵犯视交叉、海绵窦等邻近结构，引发视力下降、颅神经功能障碍等；另一方面，激素过度分泌可造成严重的全身并发症，如催乳素(prolactin)升高导致的生殖功能障碍、生长激素过量引起的肢端肥大症及心血管病变以及促甲状腺激素过量导致的继发性甲状腺功能亢进等 [ 1 ]。 PIT1谱系PitNET各亚型的治疗方案不同：催乳素瘤以多巴胺激动剂作为一线治疗方案，常用药物卡麦角林(cabergoline)和溴隐亭(bromocriptine)对催乳素瘤的生化控制率分别达79.7%和68.0% [ 3 ]；而生长激素瘤与促甲状腺激素瘤则仍以经蝶窦手术切除作为首选治疗策略，前者术后对微腺瘤的生化缓解率可达68.1%~87.6%，但对于直径≥10 mm的大腺瘤，这一比例骤降至41.0%~64.4% [ 1 ]。生长抑素类似物(somatostatin analogs, SSAs)一般作为手术的补充，用于术后残留或无法手术病灶的长期生化控制 [ 4 ]。研究显示，其对促甲状腺激素瘤疗效良好，长期生化控制率可达81%，但生长激素瘤对SSAs的应答率差异较大，且总体生化控制率仅55% [ 4 ]。然而，临床上PIT1谱系PitNET的药物治疗仍面临相当的局限性。10%~20%的催乳素瘤对卡麦角林表现出原发或继发性耐药，生长激素瘤对SSAs相对较低的应答率使得药物治疗难以成为其首选方案 [ 4 , 5 ]。此外，药物相关不良反应亦在部分患者中限制了其长期应用，如多巴胺激动剂潜在的冲动控制障碍(impulse control disorders, ICDs)，SSAs奥曲肽/兰瑞肽引发的胆石症，帕瑞肽导致的糖代谢紊乱等 [ 6 ]。总体而言，当前药物治疗瓶颈在于靶点相对单一、临床适应证局限与缺乏耐药替代手段。因此，深入探索PIT1谱系PitNET增殖、侵袭及激素分泌的分子机制，以寻找更特异、有效且安全的创新药物靶点具有重要的临床意义。一、抑制PIT1谱系肿瘤的生长并诱导肿瘤细胞死亡近期研究显示，多种分子机制涉及PIT1谱系肿瘤的增殖或侵袭行为。(1)促瘤信号通路过度激活，例如磷脂酰肌醇3激酶(phosphatidylinositol 3-kinase, PI3K)-蛋白激酶B(protein kinase B, Akt)-哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin, mTOR)、JAK激酶(Janus kinase, JAK)-信号转导及转录激活因子(signal transducer and activator of transcription, STAT)、丝裂原活化蛋白激酶(mitogen-activated protein kinase, MAPK)-细胞外信号调节激酶(extracellular signal-regulated kinase, ERK)、整合素-黏附信号及抗氧化-代谢信号通路。(2)表观遗传与转录调控的异常。(3)铜离子代谢途径。对于PI3K-Akt-mTOR通路，Wu等 [ 7 ]和Zhang等 [ 8 ]的研究显示，长链非编码RNA(long non-coding RNA, lncRNA)H19可通过与哺乳动物雷帕霉素靶蛋白调控相关蛋白(regulatory-associated protein of mammalian target of rapamycin, Raptor)竞争性结合真核翻译起始因子4E结合蛋白1(eukaryotic translation initiation factor 4E-binding protein 1, 4E-BP1)的雷帕霉素靶蛋白信号基序(target of rapamycin signaling motif, TOS motif)，特异性阻断哺乳动物雷帕霉素靶蛋白复合物1(mammalian target of rapamycin complex 1, mTORC1)对4E-BP1的磷酸化从而抑制该通路，直接抑制原位瘤的生长或借助外泌体(exo-H19)实现跨细胞传递发挥远端肿瘤抑制效应 [ 7 , 8 ]。Yao等 [ 9 ]也揭示了靶向含DEP结构域的哺乳动物雷帕霉素靶蛋白相互作用蛋白(DEP domain-containing mammalian target of rapamycin-interacting protein, DEPTOR)对于治疗PitNET的可行性。Sun等 [ 10 ]提出鞘氨醇激酶1(sphingosine kinase 1, SPHK1)-1-磷酸鞘氨醇(sphingosine-1-phosphate/sphing-osine, S1P)-1-磷酸鞘氨醇受体2(1-phosphate receptor 2, S1PR2)轴通过激活Akt-环磷酸腺苷(cyclic adenosine monophosphate, cAMP)反应元件结合蛋白(cAMP response element-binding protein, CREB)通路驱动生长激素瘤增殖，使用S1PR2抑制剂JTE-013给药28 d后可使裸鼠移植瘤体积缩小53%。JAK-STAT通路还可通过调控上皮-间充质转化(epithelial-mesenchymal transition, EMT)参与PitNET的侵袭与药物耐药。Gil等 [ 11 ]的研究显示，EMT在稀疏颗粒状生长激素细胞腺瘤(sparsely granulated somatotroph adenoma, SGST)中可通过干扰生长抑素受体2(somatostatin receptor 2, SSTR2)的选择性剪接，促进肿瘤细胞的增殖并削弱SSAs的疗效，STAT3抑制剂STX-0119可显著抑制肿瘤EMT、增殖与生长激素分泌。对于MAPK-ERK通路，Liu等 [ 12 ]通过药物筛选显示，非美诺司他(Fimepinostat)与奎诺司他(Quisinostat)可通过调控含三结构域蛋白21(tripartite motif-containing protein 21, TRIM21)的泛素化降解水平，影响ERK1/2的磷酸化，从而抑制GH3细胞皮下移植瘤生长。整合素β1(integrin β1, ITGB1)-黏着斑激酶(focal adhesion kinase, FAK)轴参与了PitNET的增殖、黏附与侵袭。在Knosp≥3级的高侵袭性肿瘤中出现明显激活，Xing等 [ 13 ]的研究显示，使用ITGB1靶向抑制剂可显著抑制下游FAK-PI3K-Akt和FAK-MAPK-ERK通路的激活，并阻断α去整合素金属蛋白酶22(a disintegrin and metalloprotease 22, ADAM22)对PitNET增殖与迁移的促进作用。此外，Cheng等 [ 14 ]通过垂体瘤类器官模型筛选显示，染料木黄酮(Genistein)可通过抑制FAK通路实现对多巴胺激动剂耐药催乳素瘤的增殖抑制。核因子红细胞2相关因子2(nuclear factor erythroid 2-related factor 2, Nrf2)是参与肿瘤增殖与转移的重要蛋白。Cheng等 [ 15 ]通过药物筛选显示，帕比司他(Panobinostat)可通过靶向抑制Nrf2从而抑制PitNET增殖，且帕比司他与Nrf2抑制剂ML385联用具有协同效应。这些研究深入探索了与PitNET增殖和侵袭相关的信号通路，揭示了一些关键的分子可能作为新的药物靶点。除了肿瘤相关信号通路的异常之外，表观遗传与转录水平调控异常也会促进肿瘤的生长与侵袭。含溴结构域蛋白4(bromodomain-containing protein 4, BRD4)是表观遗传的重要分子，通过识别并结合组蛋白乙酰化位点调控基因转录。Shi等 [ 16 ]的研究显示，BRD4在生长激素瘤中呈高表达，通过靶向降解剂ZBC-260抑制BRD4功能可诱导GH3细胞G2/M期阻滞并促进凋亡，同时下调MYC、B细胞淋巴瘤因子2(B-cell lymphoma 2, Bcl2)蛋白水平。野生型芳香烃受体相互作用蛋白(wild-type aryl hydrocarbon receptor interacting protein, AIP)是重要的抑癌因子之一。Cai等 [ 17 ]的研究显示，在AIP低表达生长激素瘤中，通用转录因子ⅡB(general transcription factor ⅡB, GTF2B)在S65位点磷酸化后可通过结合基因间区-5′非翻译区(intergenic region-5′ untranslated region, IG-5U)上调AIP表达，进而抑制生长激素瘤的增殖与侵袭性，揭示了靶向GTF2B对特定分子表型生长激素瘤的治疗潜力( 图1 )。图1 催乳素瘤与生长激素瘤的增殖相关机制与关键靶点此外，靶向铜离子代谢途径也为控制PitNET增殖提供新策略。Huang等 [ 19 ]的研究显示，双硫仑等铜离子载体在荷铜情况下可通过诱导铜死亡杀伤PitNET，治疗21 d后GH3细胞移植瘤体积缩小60%。Feng等 [ 20 ]的研究也显示，聚乙烯亚胺(polyethyleneimine, PEI)组装的含铜纳米材料可通过线粒体-自噬途径高效杀伤PitNET。二、控制PIT1谱系肿瘤的激素异常激素相关转录因子活性异常升高是PitNET激素过度合成的直接原因，相关转录因子也是抑制激素合成的关键靶点。雌激素受体α(estrogen receptor α，ERα)具有核受体与转录因子的双重属性，与催乳素合成高度相关。Zhang等 [ 21 ]的研究显示，在GH3细胞中采取ERα特异性拮抗剂ICI182780处理或利用微小RNA(microRNA, miR)-130a-3p抑制ERα表达可减少60%的催乳素合成与分泌。该研究提示，靶向转录因子可为控制激素高分泌的有效途径。通过抑制激素的分泌从而控制PitNET激素异常是另一个重要的研究方向。G蛋白偶联受体(G protein-coupled receptor, GPCR)SSTR2与多巴胺受体D2(dopamine receptor D2, DRD2)是负向调控垂体激素分泌的核心受体，其功能异常(如内吞/降解、信号通路干扰)常导致分泌失控及药物耐药。部分催乳素瘤因DRD2泛素化-内吞降解导致多巴胺激动剂耐药。Liu等 [ 5 ]的研究显示，靶向抑制E3泛素化酶Kelch重复和BTB结构域蛋白6/7(Kelch repeat and BTB domain-containing protein 6/7, KBTBD6/7)或膜受体内吞相关蛋白可减少DRD2的降解，大幅提高催乳素瘤对卡麦角林的反应性。Mangili等 [ 22 ]的研究显示，细胞骨架蛋白相关通路cAMP-蛋白激酶A(protein kinase A, PKA)-细丝蛋白A(filamin A, FLNA)的激活可显著抑制DRD2信号通路，进而阻断多巴胺激动剂对催乳素分泌的抑制作用，PKA抑制剂H89可解除这一干扰并增强卡麦角林的疗效。Zhao等 [ 23 ]的研究显示，SSTR2下游同时激活抑制激素分泌的Gi/o通路与介导受体内吞的β-抑制蛋白(β-arrestin)通路。值得关注的是，新获批非肽类SSTR2抑制剂帕妥索汀(Paltusotine)不仅在剂型上实现口服给药的突破，更在分子层面展现出克服耐药的潜力。其通过Gi偏向性激动作用，在细胞实验中使受体内化率降低60%，大幅减少SSTR2脱敏与生长激素瘤的耐药风险，为后续其他GPCR靶点新药的开发提供了一个重要方向。除经典的抑制型GPCR(DRD2/SSTR2)外，激活型GPCR的表达或活性异常是驱动激素分泌的另一类关键机制。Abboud等 [ 24 ]的研究显示，生长激素瘤中G蛋白偶联受体101(G protein-coupled receptor 101, GPR101)存在异常高表达，通过组成性激活兴奋性G蛋白(stimulatory G protein, Gs)-cAMP-PKA及Gq蛋白(Gq protein, Gq)-磷脂酶Cβ(phospholipase Cβ，PLCβ)-二酰甘油(diacylglycerol, DAG)信号协同促进生长激素合成与分泌，且该效应独立于肿瘤细胞增殖调控。该研究提示，GPR101是控制生长激素瘤激素过量分泌的潜在靶点( 图2 )。图2 催乳素瘤与生长激素瘤的激素合成/分泌相关机制与关键靶点三、调控PIT1谱系肿瘤微环境(tumor microenvi-ronment, TME) TME是由围绕肿瘤细胞的免疫细胞、基质细胞、细胞外基质及细胞因子构成的复杂动态体系。作为肿瘤进展与治疗响应的关键调控因素，靶向TME的策略已在多种肿瘤中展现出治疗前景——在黑色素瘤中，通过靶向阻断前列腺素E2(prostaglandin E2, PGE 2)或恢复Ⅰ型干扰素(type Ⅰ interferon, IFN-Ⅰ)信号可重塑免疫许可型TME，解除耐药肿瘤对过继性T细胞治疗(adoptive T-cell therapy, ACT)的抵抗 [ 25 ]；在胰腺癌与卵巢癌中，改造嵌合抗原受体自然杀伤细胞(chimeric antigen receptor natural killer cells, CAR-NK)使其分泌新白细胞介素2/15 (neoleukin-2/15, Neo-2/15)，可通过激活STAT5/Akt、上调MYC/核呼吸因子1(nuclear respiratory factor 1, NRF1)增强其TME适应能力，提高存续能力与抑瘤作用 [ 26 ]。 PitNET常被归为"冷肿瘤"，其微环境中免疫细胞浸润密度偏低，且具有抗肿瘤活性的CD8 ＋T细胞、NK细胞多处于功能耗竭状态 [ 27 ]。然而，Lin等 [ 28 ]的单细胞组学研究显示，PIT1谱系中表现出显著的免疫高浸润特征。相比其他PitNET谱系，其内部富集了更高水平的巨噬细胞、CD4 ＋/CD8 ＋T细胞与NK细胞，这些免疫细胞并非功能耗竭，而是处于一种免疫平衡状态 [ 28 ]。髓系组分中，糖蛋白非转移性黑色素瘤蛋白B ＋(glycoprotein non-metastatic melanoma protein B ＋，GPNMB ＋)巨噬细胞被证实在PIT1谱系中特征性分布，其具有明显抗炎效应，且可能通过能量供应支持POU结构域家族1成员1 ＋(POU class 1 homeobox 1 ＋，POU1F1 ＋)肿瘤细胞的生长 [ 28 ]。Su等 [ 29 ]的研究显示，分泌型磷蛋白1 ＋(secreted phosphoprotein 1 ＋，SPP1 ＋)巨噬细胞是驱动侵袭性PitNET的关键，其通过SPP1-整合素αV(integrin αV, ITGAV)/ITGB1通路激活肿瘤细胞内的迁移信号，促进肿瘤侵袭。研究显示，ITGB1-FAK轴促进PitNET肿瘤细胞生长，因此靶向抑制ITGB1或可针对肿瘤自身增殖与微环境促瘤作用发挥双重治疗效益。四、PIT1谱系肿瘤药物研发的挑战尽管基于药物筛选和机制探索，诸多PIT1谱系PitNET的创新靶点已被发现，但相关新药研发仍面临多重挑战。(1) PIT1谱系内的异质性导致新药靶点作用谱窄，缺乏通用方案；而精准用药依赖生物标志物明确适用范围，相应临床检测手段却显不足——例如ITGB1、lncRNA H19等缺乏标准化检测技术。(2)药物脱靶风险。例如PKA抑制剂H89可能干扰心肌组织正常信号，增加心血管不良反应；靶向转录因子如GTF2B缺乏足够的组织特异性，极易干扰正常细胞的基因表达稳态。(3)临床证据薄弱。多数候选靶点仅停留在细胞实验或动物模型阶段，未进一步进行临床试验。然而，前沿技术与联合用药策略或许可加速PIT1谱系PitNET创新药物的开发。例如人工智能辅助药物设计可通过多组学数据整合、靶点成药性筛选与针对性药物结构设计，大幅缩短新靶点的验证与药物开发周期，是新药研发的利器 [ 30 ]；而类器官模型不仅具备高通量筛选能力，还可通过模拟体内环境辅助验证药效，更好地衔接基础研究与临床转化 [ 14 ]。此外，鉴于PIT1谱系PitNET病理生理机制及耐药通路的复杂性，联合干预方案很可能是突破的关键。对于肿瘤细胞本身，可将新受体靶点筛选、经典信号偏向性选择与关键转录因子精准调节等手段相结合，协同纠正肿瘤异常增殖与激素分泌失控，有效规避受体脱敏导致的继发性耐药；在肿瘤细胞之外，可针对性阻断以SPP1-ITGB1为代表的侵袭信号轴，并积极探索嵌合抗原受体T细胞(chimeric antigen receptor T-cell, CAR-T)、嵌合抗原受体自然杀伤细胞(chimeric antigen receptor natural killer cells, CAR-NK)等免疫治疗新技术，以多维度联合方案打破单一靶点药物的疗效瓶颈，最终实现PIT1谱系PitNET的精准治疗与全景调控。参考文献（略）扫码下载杂志官方App

2026-06-02

·BioSpace

Crinetics’ Paradigm-Shifting Portfolio and Pipeline on Display at ENDO 2026 with Six Presentations

Oral presentation features open label extension PALSONIFY™ (paltusotine) data, reinforcing its best-in-class potential in acromegaly following recent U.S. and E.U. approvals Two oral presentations of novel, investigational ACTH receptor antagonist atumelnant include full Phase 2 study results in congenital adrenal hyperplasia and data from additional patients in the Phase 1b/2a ACTH-dependent Cushing’s syndrome study SAN DIEGO, June 02, 2026 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) today announced that data from six abstracts, including oral presentations featuring PALSONIFY™ (paltusotine) and investigational candidate atumelnant, will be presented at the Endocrine Society’s Annual Meeting, ENDO 2026, June 13-16, 2026, in Chicago, IL. "At ENDO 2026, new data will be presented which increase the depth of clinical evidence supporting the long-term safety and efficacy of Palsonify for the treatment of acromegaly," said Dr. Alan Krasner, M.D., Chief Endocrinologist, Crinetics. “In addition, updated data will be presented characterizing the potential of atumelnant to set an uncompromising bar for treating diseases of ACTH excess. I have often been frustrated by the lack of optimized treatments for these and many other difficult to manage endocrine conditions. At Crinetics, we are continuously working with many outstanding external investigator colleagues to redefine the possibilities.” Three abstracts will report data related to PALSONIFY in acromegaly, including an oral presentation featuring long-term (up to two years) efficacy and pooled safety data from the PATHFNDR-1 and PATHFNDR-2 open-label extension (OLE) studies. Additionally, one poster presentation evaluates real-world biochemical control in acromegaly using U.S. claims and laboratory data to identify areas of unmet need for patients and to inform optimization of acromegaly management. Another poster presentation assesses long-term safety and efficacy of PALSONIFY in combination with cabergoline from the ACROBAT Advance trial. Three abstracts from Crinetics’ atumelnant clinical development program will also be presented, including oral presentations of full Phase 2 data in congenital adrenal hyperplasia (CAH) and new interim results from a Phase 1b/2a study in ACTH-dependent Cushing’s syndrome. An additional rapid-fire presentation highlights dose selection data for the Phase 3 trial in CAH. Crinetics will also present a product theater June 15 from 12:30-1:30 CST, titled “Advancing Acromegaly Management: Bridging Clinical Evidence and the Patient Journey with PALSONIFY™ (paltusotine). Presenters include Dr. Anthony Heaney and a patient living with acromegaly. Presentation details are shown below. PALSONIFY™ (paltusotine) Presentations Title (oral presentation): Efficacy and Safety of Once-Daily Oral Paltusotine in Patients with Acromegaly: Up to 2 years in the PATHFNDR-1 and PATHFNDR-2 Open-Label Extension Studies Authors: Gadelha, M.R. “et. al." Date/Time: June 14, 1:45 PM – 3:15 PM CT Location : Room W183BC Title (poster presentation): Long-Term Safety and Efficacy of Once-Daily Oral Paltusotine in Combination With Cabergoline for the Treatment of Patients With Acromegaly Authors: Gadelha. M.R. “et. al." Date/Time: June 14; 12:00 PM – 1:30 pm CT Location: ENDO Expo Hall, McCormick Place West Title (poster presentation) : Real-World Biochemical Control in Acromegaly: Insights from US Claims and Laboratory Data Authors: Wang, S “et. al." Date/Time: June 15; 12:00 PM – 1:30 pm CT Location: ENDO Expo Hall, McCormick Place West Atumelnant Presentations Title (oral presentation) : Once Daily Atumelnant (CRN04894) Enables Lowering of Glucocorticoid Doses With Sustained Androgen Reduction in Adults With Congenital Adrenal Hyperplasia Authors: Srirangalingam, U., “et. al." Date/Time: June 14, 1:45 PM – 3:15 PM CT Location: Room W184ABC Title (oral presentation): ‘Block And Replace’ Atumelnant (CRN04894) And Physiologic Hydrocortisone Replacement Rapidly Controls Hypercortisolism In ACTH-dependent Cushing Syndrome Authors: Elenius, H., “et al” Date/Time: June 14, 3:30 PM – 4:15 PM CT Location: Room W187 Title (rapid-fire and poster presentations) : Model-Informed Atumelnant Dose Selection for a Phase 3 Study in Adult Patients With Classic Congenital Adrenal Hyperplasia Authors: Curd, L., “et. al." Dates/Times: Rapid Fire: June 14, 1:45 PM - 3:15 PM CT Poster: June 15, 12:00 PM – 1:30 PM CT Locations: Rapid Fire: Room W184ABC Poster: ENDO Expo Hall, McCormick Place West About PALSONIFY™ (Paltusotine) PALSONIFY, a selectively-targeted somatostatin receptor type 2 (SST2) nonpeptide agonist, is the first and only once-daily, oral therapy approved for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. In Phase 3 studies, once-daily, oral PALSONIFY maintained IGF-1 levels and symptom control in patients with acromegaly who were switched from monthly injectable medications (PATHFNDR-1) and rapidly decreased IGF-1 levels and symptom burden in medically untreated acromegaly patients (PATHFNDR-2). IGF-1 is the primary biomarker endocrinologists use to manage acromegaly patients. Paltusotine is also in Phase 3 clinical development for carcinoid syndrome associated with neuroendocrine tumors (CAREFNDR). Results from a Phase 2 study in carcinoid syndrome demonstrated rapid and sustained reductions in flushing episodes and bowel movement frequency, which are the most common symptoms of carcinoid syndrome. PALSONIFY is approved in the U.S. for the first-line treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. It is also approved for use in the EU for the medical treatment of adult patients with acromegaly. About Atumelnant Atumelnant, Crinetics’ second investigational compound, is the first once-daily, oral adrenocorticotropic hormone (ACTH) receptor antagonist that acts selectively at the melanocortin type 2 receptor (MC2R) on the adrenal gland. Diseases associated with excess ACTH can have significant impact on physical and mental health. Atumelnant has exhibited strong binding affinity for MC2R in preclinical models and has demonstrated suppression of adrenally derived glucocorticoids and androgens that are under the control of ACTH. Data from a 12-week Phase 2 study demonstrated compelling treatment benefits of atumelnant, evidenced by the rapid, substantial and sustained statistically significant reductions in key CAH disease related biomarkers, including androstenedione and 17-hydroxyprogesterone, in a diverse population. Atumelnant is in development for congenital adrenal hyperplasia and ACTH-dependent Cushing’s syndrome, with the Phase 3 CALM-CAH trial and a Phase 1/2b trial in ADCS currently enrolling patients. About Crinetics Pharmaceuticals Crinetics Pharmaceuticals is a global pharmaceutical company committed to transforming the treatment of endocrine diseases and endocrine-related tumors through science rooted in patient needs. Crinetics is focused on discovering, developing, and commercializing novel therapies, with a core expertise in targeting G-protein coupled receptors (GPCRs) with small molecules that have specifically tailored pharmacology and properties. Crinetics’ first commercial product, PALSONIFY™ (paltusotine), is the first once-daily, oral treatment approved by the U.S. FDA and EMA for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. Paltusotine is also in clinical development for carcinoid syndrome associated with neuroendocrine tumors. Crinetics’ deep pipeline of 10+ disclosed programs includes late-stage investigational candidate atumelnant, which is currently in development for congenital adrenal hyperplasia and ACTH-dependent Cushing’s syndrome, and CRN09682, a nonpeptide drug conjugate candidate that is being developed to treat somatostatin receptor 2 (SST2) expressing neuroendocrine tumors and other SST2 expressing solid tumors. Additional discovery programs are focused on a variety of endocrine targets such as thyroid stimulating hormone (TSH), parathyroid hormone (PTH), somatostatin receptor 3 (SST3), growth hormone (GH), glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP), as well as GPCR-targeted oncology indications. PALSONIFY™ (paltusotine) INDICATION: PALSONIFY is a somatostatin receptor agonist indicated for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS: Cholelithiasis and Its Complications: Cholelithiasis, including related complications such as acute cholecystitis and pancreatitis, have been reported. Monitor patients periodically. Discontinue PALSONIFY if complications of cholelithiasis occur and treat appropriately. Hyperglycemia and Hypoglycemia: Hyperglycemia, diabetes mellitus, or hypoglycemia, may occur. Monitor blood glucose levels when PALSONIFY treatment is initiated or when dosage is altered. Adjust antidiabetic treatment accordingly. Cardiovascular Abnormalities: Cardiac conduction abnormalities and other ECG changes such as PR interval prolongation, bradycardia, sinus arrest, and atrioventricular block may occur in patients with acromegaly and were reported in PALSONIFY clinical trials. Dosage adjustments of concomitant drugs that have bradycardic effects may be necessary. Thyroid Function Abnormalities: Somatostatin analogs may suppress the secretion of thyroid-stimulating hormone, which may result in hypothyroidism. Periodic assessment of thyroid function is recommended. Steatorrhea and Malabsorption of Dietary Fats: Somatostatin analog treatment may result in malabsorption of dietary fats and subsequent symptoms of steatorrhea, loose stools, abdominal bloating, and weight loss. If new or worsening symptoms are reported with PALSONIFY, evaluate patients for potential pancreatic exocrine insufficiency and manage accordingly. Vitamin B12 Deficiency: Vitamin B12 deficiency may occur. Monitor vitamin B12 levels, if clinically indicated. ADVERSE REACTIONS: Most common adverse reactions (>5%) are diarrhea, abdominal pain, nausea, decreased appetite, sinus bradycardia, hyperglycemia, palpitations, and gastroenteritis. DRUG INTERACTIONS: Strong or Moderate CYP3A4 Inducers: may decrease PALSONIFY exposure. May require an increased dosage of PALSONIFY. Proton Pump Inhibitors: may decrease PALSONIFY exposure. May require an increased dosage of PALSONIFY. Avoid concomitant use of proton pump inhibitors in patients who are already on PALSONIFY 60 mg. Cyclosporine: may decrease cyclosporine exposure. May require cyclosporine dosage adjustment when used with PALSONIFY; follow therapeutic monitoring recommendations. Please report adverse events to Crinetics Pharmaceuticals at 1-833-CRN-INFO (1-833-276-4636) or FDA at 1-800-FDA-1088 or . Please see Full Prescribing Information including Patient Information . Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward-looking statements, including statements regarding the plans and timelines for the clinical development of atumelnant and paltusotine for the treatment of carcinoid syndrome; or the potential for our development candidates to transition to clinical development. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential,” “upcoming” or “continue” or the negative of these terms or other similar expressions. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, including, without limitation, we may not be able to obtain, maintain and enforce our patents and other intellectual property rights, and it may be prohibitively difficult or costly to protect such rights; geopolitical events may disrupt Crinetics’ business and that of the third parties on which it depends, including delaying or otherwise disrupting clinical studies and preclinical studies, manufacturing and supply chain, or impairing employee productivity; unexpected adverse side effects, complications and/or drug interactions or inadequate efficacy of the Company’s product candidates that may limit their development, regulatory approval and/or commercialization; the Company’s dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing; regulatory developments or political changes, including policies related to pricing and pharmaceutical drug reimbursement, in the United States and foreign countries; the timing and outcome of research, development and regulatory review is uncertain, and Crinetics’ drug candidates may not advance in development or be approved for marketing; Crinetics may use its capital resources sooner than expected or our cash burn rate may accelerate; any future impacts to our business resulting from geopolitical developments outside our control; and the other risks and uncertainties described in the Company’s periodic filings with the Securities and Exchange Commission (SEC). The events and circumstances reflected in the company’s forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Additional information on risks facing Crinetics can be found under the heading “Risk Factors” in Crinetics’ periodic filings with the SEC, including its annual report on Form 10-K for the year ended December 31, 2025. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Except as required by applicable law, Crinetics does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Media: Natalie Badillo Head of Corporate Communications nbadillo@crinetics.com (858) 345-6075 Investors: Gyathri Diwakar Head of Investor Relations gdiwakar@crinetics.com (858) 345-6340

临床2期临床结果临床3期上市批准

100 项与卡麦角林相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00987	卡麦角林	N04BC06 G02CB03	DB00248

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适应症	国家/地区	公司	日期
泌乳障碍	日本	Pfizer Japan, Inc.	2003-04-16
帕金森病	日本	Pfizer Japan, Inc.	1999-06-16
高催乳素血症	澳大利亚	Pfizer Inc.	1995-04-21

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
不宁腿综合征	临床3期	-	Pfizer Inc.	2002-11-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT06029673 (Pubmed \| Obstet Gynecol)	临床2期	流产	138	Cabergoline 1 mg	構齋窪製膚鹽膚衊範壓(餘繭襯淵製廠願遞壓鑰) = 簾艱簾繭夢網憲網製醖願製糧窪網積齋構壓積 (網獵衊選築鏇構齋簾鑰 ) 更多	积极	2026-02-01
				Placebo	構齋窪製膚鹽膚衊範壓(餘繭襯淵製廠願遞壓鑰) = 鑰衊簾壓窪願艱壓壓衊願製糧窪網積齋構壓積 (網獵衊選築鏇構齋簾鑰 ) 更多
NCT06029673 (eLISTA, CTgov)	临床2期	妊娠中期流产 \| 泌乳障碍	69	Cabergoline 1 MG (Cabergoline)	衊鹽淵膚積鹹築繭網獵 = 簾顧網憲簾築觸夢壓夢範艱蓋齋鏇蓋選憲窪繭 (顧願選鹽糧醖構憲襯艱, 範製顧膚繭構憲糧蓋簾 ~ 範鏇獵餘製淵窪獵鬱膚) 更多	-	2025-10-03
				Placebo (Placebo)	衊鹽淵膚積鹹築繭網獵 = 餘製鬱壓觸窪構顧鏇製範艱蓋齋鏇蓋選憲窪繭 (顧願選鹽糧醖構憲襯艱, 壓願築壓範鏇餘積憲網 ~ 夢獵構鏇憲獵廠鹽範蓋) 更多
NCT05525611 (Pubmed \| PLoS One)	N/A	偏头痛	36	Cabergoline 0.5 mg	願淵憲鏇衊獵壓膚憲網(鑰廠糧窪範窪網觸壓夢) = 蓋鹹窪壓積顧鹽鑰蓋窪獵選糧繭獵餘積壓構觸 (顧鏇齋鹹衊願餘糧築鹹, 4.1)	积极	2025-04-01
				Placebo	願淵憲鏇衊獵壓膚憲網(鑰廠糧窪範窪網觸壓夢) = 膚膚糧夢壓醖鏇繭製壓獵選糧繭獵餘積壓構觸 (顧鏇齋鹹衊願餘糧築鹹, 5.3)
NCT01794793 (B2412, CTgov)	临床4期	倾倒综合征 \| 垂体肿瘤 \| 肢端肥大症 ... 更多	337	Cabergoline+Pasireotide (Pasireotide Subcutaneous)	觸願遞構憲鹹憲醖鹽遞 = 範淵遞遞鑰鬱憲鏇窪選鏇淵艱製觸艱獵製淵構 (鹽築膚網餘鬱艱夢構觸, 鑰膚壓鬱獵齋獵獵鬱夢 ~ 壓壓觸廠範淵鏇範簾艱) 更多	-	2024-08-28
				Pasireotide LAR (Pasireotide Long Acting Release (LAR))	觸願遞構憲鹹憲醖鹽遞 = 衊獵鑰齋廠遞鹹窪積願鏇淵艱製觸艱獵製淵構 (鹽築膚網餘鬱艱夢構觸, 遞廠觸網顧餘膚鑰餘壓 ~ 餘簾憲窪窪餘糧襯製鑰) 更多
NCT05024422 (Pubmed \| Am J Obstet Gynecol)	临床3期	母乳喂养	-	Cabergoline	鹹餘膚醖網網積膚繭餘(鏇鏇簾壓壓膚襯淵醖簾) = 遞艱蓋顧夢衊齋遞構鑰淵醖積鹽顧網遞願糧簾 (鹹艱憲選構觸衊淵簾顧 ) 更多	积极	2024-05-01
				Pyridoxine	鹹餘膚醖網網積膚繭餘(鏇鏇簾壓壓膚襯淵醖簾) = 選築齋窪遞製簾獵鏇願淵醖積鹽顧網遞願糧簾 (鹹艱憲選構觸衊淵簾顧 ) 更多
NCT04701333 (Pubmed \| Obstet Gynecol)	临床2期	流产	73	Cabergoline 1 mg	蓋鹽窪遞壓鑰淵壓觸鬱(糧襯觸願構簾餘繭壓憲) = 鑰鹹選築壓獵衊衊製艱襯鏇艱願壓鹹選範獵遞 (繭構選獵齋製膚膚鏇鬱 )	积极	2023-06-01
				Placebo	蓋鹽窪遞壓鑰淵壓觸鬱(糧襯觸願構簾餘繭壓憲) = 衊鏇繭廠鹽廠夢觸獵鑰襯鏇艱願壓鹹選範獵遞 (繭構選獵齋製膚膚鏇鬱 )
NCT04701333 (LISTA, CTgov)	临床2期	母乳喂养 \| 妊娠中期流产	73	Cabergoline 1 MG (Cabergoline)	襯鏇廠築遞鹽築顧簾選 = 願繭淵鹽繭鬱壓觸餘構鹹觸繭簾繭構鹹膚構鏇 (夢構齋獵廠鏇夢築淵膚, 鹹艱窪範廠繭蓋齋壓蓋 ~ 鏇築觸衊積網艱製積鏇) 更多	-	2023-04-05
				Placebo (Placebo)	襯鏇廠築遞鹽築顧簾選 = 壓夢製鹹願築艱襯夢觸鹹觸繭簾繭構鹹膚構鏇 (夢構齋獵廠鏇夢築淵膚, 淵廠醖衊壓淵顧醖觸窪 ~ 觸顧醖夢蓋夢範齋遞壓) 更多
ASTRO2020	N/A	胶质母细胞瘤	-	Dose-Intensified Chemoradiation (Standard chemoradiation)	觸繭蓋糧積壓網構簾築(糧鑰範觸艱糧蓋餘廠顧) = 2 cases observed 遞觸遞憲衊觸廠製鏇築 (齋廠製鹹鹹夢顧襯願範 ) 更多	-	2020-11-01
NCT02542410 (CTgov)	临床2期	子宫内膜异位症 \| 疼痛 \| 盆腔疼痛	10	Norethindrone acetate (Control)	窪製艱鬱膚壓淵繭襯糧(鬱願憲鹹夢膚選憲願壓) = 築繭鏇簾鏇構範網糧艱築鹽繭簾糧壓窪鏇鑰蓋 (鑰鹹鏇襯製鹽艱範繭鬱, 簾淵艱鹽構鹽獵夢簾餘 ~ 蓋範觸鬱簾糧製鹽壓獵) 更多	-	2020-02-05
				Cabergoline (Experimental)	窪製艱鬱膚壓淵繭襯糧(鬱願憲鹹夢膚選憲願壓) = 簾憲鹹遞襯繭製構艱觸築鹽繭簾糧壓窪鏇鑰蓋 (鑰鹹鏇襯製鹽艱範繭鬱, 鬱願鑰鑰獵鏇簾築餘淵 ~ 鹽簾膚願顧願齋繭鏇膚) 更多
SAT-474 (ENDO2019)	N/A	催乳素瘤 Prolactin concentration	15	Cabergoline 0.25-0.5 mg weekly	鏇築糧廠鑰艱築獵夢鏇(廠艱衊製廠繭膚鏇鹽構) = 鬱糧窪糧積鏇窪簾壓膚餘齋顧鬱鑰窪鬱醖糧鹹 (憲窪壓壓鬱簾鬱壓顧願 )	积极	2019-04-30