更新于：2024-11-01

SSTR5 x D2 receptor x SSTR2

更新于：2024-11-01

基本信息

关联

项与 SSTR5 x D2 receptor x SSTR2 相关的药物

Dopastatin

靶点

D2 receptor x SSTR2 x SSTR5

作用机制

D2 receptor激动剂 [+2]

在研机构-

原研机构

Ipsen SA

在研适应症-

非在研适应症

肢端肥大症 [+4]

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

项与 SSTR5 x D2 receptor x SSTR2 相关的临床试验

EUCTR2019-003142-32-HU / Not yet recruiting临床2期

A One Year, Randomized, Double-Blind, Placebo-Controlled Study of TBR-760 in Adult Patients with Non-Functioning Pituitary Adenomas

开始日期2020-07-08

申办/合作机构

Tiburio Therapeutics, Inc.初创企业

NCT04335357 / Unknown status临床2期

A One Year, Randomized, Double-Blind, Placebo-Controlled Study of TBR-760 in Adult Patients With Non-Functioning Pituitary Adenomas

This is a randomized, double-blind, placebo-controlled study to assess the safety, tolerability, efficacy, PK, and PD of the chimeric dopamine-somatostatin receptor agonist, TBR-760, in adult patients with NFPA over 52 weeks.

开始日期2020-05-01

申办/合作机构

Tiburio Therapeutics, Inc.初创企业

NCT01018953 / Terminated临床2期

Phase II, Open, Adaptive, Dose Escalating, Multicentre Titration Study to Assess the Efficacy and Safety of Repeated Subcutaneous Administration of Different Doses of BIM 23A760 in Patients With Carcinoid Syndrome

The purpose of the protocol is to assess the efficacy and safety of BIM 23A760 on patient's overall satisfaction in terms of symptom relief (diarrhoea and/or flushes) in patients with carcinoid syndrome after 24 weeks of treatment.

开始日期2010-02-01

申办/合作机构

Ipsen SA

100 项与 SSTR5 x D2 receptor x SSTR2 相关的临床结果

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100 项与 SSTR5 x D2 receptor x SSTR2 相关的转化医学

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0 项与 SSTR5 x D2 receptor x SSTR2 相关的专利（医药）

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项与 SSTR5 x D2 receptor x SSTR2 相关的文献（医药）

2020-06-01·Journal of Endocrinological Investigation

Is Somatostatin Receptor and Dopamine Receptor profiling useful in the management of silent somatotroph tumors?

Letter

作者: Lamas, C ; Picó, A ; López-Muñoz, B ; García-Martínez, A ; Cámara, R ; Fajardo, C ; Torregrosa-Quesada, M E ; Martínez-López, S

Silent somatotroph tumors (sSTs) are pituitary neuroendocrine tumors (PitNETs) which do not give rise to the clinical syndrome of acromegaly. Differently to their functioning counterparts, the adjuvant medical treatment with somatostatin analogues (SSAs) or dopamine receptors agonists (DAs) has been scarcely addressed in these tumors. As preliminary results of an ongoing research on silencing mechanisms involved in the pathogenesis of sSTs, we have characterized by qRT-PCR the expression of SSTRs and DRDs in a large series of 18 silent and 68 functioning STs. Although the expression of SSTR2 and SSTR5 was lower in sSTs than in functioning ones, we found a negative correlation between SSTR2 and the tumor size of the sSTs. Additionally, levels of expression of DRD2 were similar between the two subtypes suggesting a possible basis for the treatment of these tumors with SSAs and DAs.

2020-06-01·Endocrine-Related Cancer2区 · 医学

Molecular profiling for acromegaly treatment: a validation study

2区 · 医学

Article

作者: Webb, Susan M ; Villabona, Carles ; Marques-Pamies, Montserrat ; Picó, Antonio ; Valassi, Elena ; Serra, Guillermo ; Obiols, Gabriel ; Blanco, Alberto ; Sampedro-Nuñez, Miguel ; García-Martínez, Araceli ; Alvarez, Clara V ; Fajardo-Montañana, Carmen ; del Pozo, Carlos ; Bernabéu, Ignacio ; Buj, Raquel ; Gil, Joan ; Puig-Domingo, Manel ; Jordà, Mireia ; Carrato, Cristina ; Salinas, Isabel ; Marazuela, Mónica ; Pons, Laura ; Cámara, Rosa

Pharmacologic treatment of acromegaly is currently based upon assay-error strategy, the first-generation somatostatin receptor ligands (SRL) being the first-line treatment. However, about 50% of patients do not respond adequately to SRL. Our objective was to evaluate the potential usefulness of different molecular markers as predictors of response to SRL. We used somatotropinoma tissue obtained after surgery from a national cohort of 100 acromegalic patients. Seventy-one patients were treated with SRL during at least 6 months under maximal therapeutic doses according to IGF1 values. We analyzed the expression of SSTR2, SSTR5, AIP, CDH1 (E-cadherin), MKI67 (Ki-67), KLK10, DRD2, ARRB1, GHRL, In1-Ghrelin, PLAGL1 and PEBP1 (RKIP) by RT-qPCR and mutations in GNAS gene by Sanger sequencing. The response to SRL was categorized as complete response (CR), partial (PR) or non-response (NR) if IGF1 was normal, between >2<3 SDS or >3 SDS IGF1 at 6 months of follow-up, respectively. From the 71 patients treated, there were 27 CR (38%), 18 PR (25%) and 26 NR (37%). SSTR2, Ki-67 and E-cadherin were associated with SRL response (P < 0.03, P < 0.01 and P < 0.003, respectively). E-cadherin was the best discriminator for response prediction (AUC = 0.74, P < 0.02, PPV of 83.7%, NPV of 72.6%), which was validated at protein level. SSTR5 expression was higher in patients pre-treated with SRL before surgery. We conclude that somatotropinomas showed heterogeneity in the expression of genes associated with SRL response. E-cadherin was the best molecular predictor of response to SRL. Thus, the inclusion of E-cadherin in subsequent treatment-decision after surgical failure may be useful in acromegaly.

2019-01-01·Journal of the Endocrine Society

Pituitary Pathology and Gene Expression in Acromegalic Cats

Article

作者: Crossley, Victoria J ; Fowkes, Robert C ; Mirczuk, Samantha M ; Niessen, Stijn J M ; Scudder, Christopher J ; Kenny, Patrick J ; Regan, Jacob T C ; McGonnell, Imelda M ; Korbonits, Márta ; Richardson, Karen M ; Hazuchova, Katarina ; Harrington, Norelene ; Church, David B ; Forcada, Yaiza ; Gostelow, Ruth

The prevalence of GH-secreting pituitary tumors in domestic cats (Felis catus) is 10-fold greater than in humans. The predominant inhibitory receptors of GH-secreting pituitary tumors are somatostatin receptors (SSTRs) and D₂ dopamine receptor (DRD2). The expression of these receptors is associated with the response to somatostatin analog and dopamine agonist treatment in human patients with acromegaly. The aim of this study was to describe pathological features of pituitaries from domestic cats with acromegaly, pituitary receptor expression, and investigate correlates with clinical data, including pituitary volume, time since diagnosis of diabetes, insulin requirement, and serum IGF1 concentration. Loss of reticulin structure was identified in 15 of 21 pituitaries, of which 10 of 15 exhibited acinar hyperplasia. SSTR1, SSTR2, SSTR5, and DRD2 mRNA were identified in the feline pituitary whereas SSTR3 and SSTR4 were not. Expression of SSTR1, SSTR2, and SSTR5 was greater in acromegalic cats compared with controls. A negative correlation was identified between DRD2 mRNA expression and pituitary volume. The loss of DRD2 expression should be investigated as a mechanism allowing the development of larger pituitary tumors.