马来酸氟诺替尼(Flunotinib maleate) - 药物靶点：CDK6 x FLT3 x JAK2_在研适应症：原发性血小板增多症后骨髓纤维化，真性红细胞增多症后骨髓纤维化，原发性骨髓纤维化_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Flonoltinib Maleate

靶点

CDK6 x FLT3 x JAK2

作用机制

CDK6抑制剂(细胞周期蛋白依赖性激酶6抑制剂)、FLT3抑制剂(酪氨酸蛋白激酶受体FLT3抑制剂)、JAK2抑制剂(酪氨酸蛋白激酶JAK2抑制剂)

治疗领域

肿瘤免疫系统疾病血液及淋巴系统疾病+ [1]

在研适应症

原发性血小板增多症后骨髓纤维化真性红细胞增多症后骨髓纤维化原发性骨髓纤维化+ [5]

非在研适应症-

原研机构

成都赜灵生物医药科技有限公司

在研机构

成都赜灵生物医药科技有限公司

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)临床2期

特殊审评-

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关联

11

项与马来酸氟诺替尼相关的临床试验

NCT06457425 / Recruiting临床2期

An Open, Positive Drug-controlled, Parallel-group, Multicenter Phase II Clinical Trial of the Efficacy, Safety, and Pharmacokinetics of Flunotinib Maleate Tablets in the Treatment of Patients With Intermediate- and High-risk Myelofibrosis

This trial adopts a multicenter, open-label, positive drug parallel control clinical trial design, planning to enroll approximately 75 MF participants. Eligible participants will be stratified and assigned in a 1:1:1 ratio to the low-dose fruquintinib maleate tablet group, high-dose fruquintinib maleate tablet group, or the ruxolitinib tablet group. Stratification factors include the Dynamic International Prognostic Scoring System (DIPSS) risk classification (intermediate-2 and high risk)

开始日期2024-05-06

申办/合作机构

成都赜灵生物医药科技有限公司

ChiCTR2400081717 / Recruiting临床1期IIT

A randomized, double-blind, placebo-controlled, dose-escalating, single-dose, oral phase I clinical study of the safety, tolerability, and pharmacokinetics of flunotinib maleate tablets in healthy adult subjects in China.

开始日期2024-03-13

申办/合作机构-

NCT06387966 / Recruiting临床1期

A Randomized, Double-blind, Placebo-controlled, Dose-escalating, Single-dose, Oral Phase I Clinical Study of the Safety, Tolerability, and Pharmacokinetics of Flunotinib Maleate Tablets in Healthy Adult Subjects in China.

Evaluate the safety and tolerability of a single increasing dose of Flibanserin Maleate tablets administered orally to healthy adult Chinese subjects; preliminarily assess the pharmacokinetic characteristics of a single dose of oral Flibanserin Maleate tablets

开始日期2024-02-29

申办/合作机构

成都赜灵生物医药科技有限公司

100 项与马来酸氟诺替尼相关的临床结果

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100 项与马来酸氟诺替尼相关的转化医学

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100 项与马来酸氟诺替尼相关的专利（医药）

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6

项与马来酸氟诺替尼相关的文献（医药）

2024-04-01·Journal of Pharmaceutical and Biomedical Analysis

Study on tissue distribution, metabolite profiling, and excretion of [14C]-labeled flonoltinib maleate in rats

Article

作者: Tang, Minghai ; Ma, Ziyan ; Chen, Lijuan

Flonoltinib Maleate (FM) is a dual-target inhibitor that selectively suppresses Janus kinase 2/FMS-like tyrosine kinase 3 (JAK2/FLT3), which is currently in phase I/IIa clinical trial in China for the treatment of myeloproliferative neoplasms (MPNs). In this research, we used [¹⁴C]-labeled FM (¹⁴C-FM) to investigate the distribution, metabolism, and excretion of FM in rats using High-Performance Liquid Chromatography coupled with High-Resolution Mass Spectrometry/Radioactivity Monitoring (HPLC-HRMS/RAM) and liquid scintillation counter. The results revealed that FM displayed widespread distribution in rats. Furthermore, FM demonstrated rapid clearance without any observed risk of organ toxicity attributed to accumulation. Profiling of FM metabolites in rat plasma, feces, urine, and bile identified a total of 17 distinct metabolites, comprising 7 phase I metabolites and 10 phase II metabolites. The major metabolic reactions involved oxygenation, dealkylation, methylation, sulfation, glucuronidation and glutathione conjugation. Based on these findings, a putative metabolic pathway of FM in rats was proposed. The overall recovery rate in the excretion experiment ranged from 93.04 % to 94.74 %. The results indicated that FM undergoes extensive hepatic metabolism in SD rats, with the majority being excreted through bile as metabolites and ultimately eliminated via feces. A minor fraction of FM (<10 %) was excreted through renal excretion in the form of urine. Integration of the current results with previous pharmacokinetic investigations of FM in rats and dogs enables a comprehensive elucidation of the in vivo ADME processes and characteristics of FM, thereby establishing a solid foundation for subsequent clinical investigations of FM.

2023-10-03·Expert Opinion on Investigational Drugs

Novel Janus-kinase (JAK) Inhibitors in Myelofibrosis

Review

作者: Eskazan, Ahmet Emre ; Ipek, Yildiz ; Kilic, Berkay ; Gunay, Ulgar Boran

INTRODUCTIONJAK inhibitors (JAKis), used in the treatment of myelofibrosis, have entered standard treatment, providing significant improvements in spleen size and symptom burden. Although splenomegaly provides a reduction and some improvement in cytopenia, there is still a way to go. Novel JAKis are being investigated to overcome barriers to treatment access, such as therapeutic challenges, intolerance, and unresponsiveness.AREAS COVEREDThis review includes the current status of JAKi treatment for myelofibrosis, mainly focusing on investigational JAKis; jaktinib, lestaurtinib, itacitinib, gandotinib, BMS-911543, ilginatinib, TQ05105, and flonoltinib maleate. MEDLINE and clinicaltrials.gov were screened to identify all completed or active studies on this topic. The outcomes of the preclinical studies and clinical trials are presented and discussed for each drug.EXPERT OPINIONIn patients with myelofibrosis, momelotinib was effective in treating anemia, whereas jaktinib was effective in both anemia and Total Symptom Score (TSS). More phase 3 studies are needed to provide more precise evidence. The increasing variety of JAKis will allow for more personalized treatment options for myelofibrosis in the future. The potential impact on disease progression, molecular responses, and the duration of this response will become important parameters for future evaluations of these drugs.

2023-05-01·Journal of Chromatography B

UPLC-MS/MS method development and application to pharmacokinetic study in rats and dogs of Flonoltinib Maleat

Article

作者: Chen, Lijuan ; Tang, Minghai ; Ye, Haoyu ; Zhou, Yanting ; Yang, Zhuang ; Wei, Panhong ; Pu, Qianlun ; Zhao, Jiajia ; Ma, Ziyan ; Wu, Rui

Flonoltinib Maleate (FM) is a novel selective inhibitor of Janus kinase 2/FMS-like tyrosine kinase 3 (JAK2/FLT3). In this study, we developed an ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method to measure the plasma concentrations of FM in rats and dogs for pharmacokinetic studies. For chromatographic separation, we used a BEH C18 column (2.1 × 50 mm, 1.7 μm particle size) in HPLC. The mobile phase A consisted of a water solution containing 0.1% formic acid (FA) and 2 mM NH₄OAc, mixed with acetonitrile (ACN) (V:V = 95:5). The mobile phase B was a water solution containing 0.1% FA and 2 mM NH₄OAc, mixed with ACN (V:V = 5:95), which was used for gradient elution. We used multiple reactive ion detection (MRM) mode and electrospray ionization positive (ESI+) mode for quantitative analysis. The standard curve was linear in the concentration range of 0.5 to 500 ng/ml in rat and dog plasma. The intra-batch and inter-batch precision (RSD%) of FM in rat and dog plasma was less than 15%. The intra-batch and inter-batch accuracy was 88.3-106.5% and 92.0-100.6% in rats, and 94.7-106.6% and 95.3-103.8% in dogs, respectively. The RSD (%) of matrix factors (MF) normalized to the internal standard (IS) of FM in rat and dog plasma was ≤5.6% and ≤3.0%, respectively. The extraction recovery and carryover were considered acceptable. When the sample concentration was higher than the upper limit of quantitation (ULOQ), the 10-fold dilution was reliable within the limits of acceptability. The UPLC-MS/MS method developed in this study was successfully applied in measuring the pharmacokinetic parameters of FM in rats and dogs after intravenous and oral administration, laying a foundation for the preclinical pharmacokinetic study of FM and providing a reference for clinical pharmacokinetic studies.

100 项与马来酸氟诺替尼相关的药物交易

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研发状态

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
原发性血小板增多症后骨髓纤维化	临床2期	中国	成都赜灵生物医药科技有限公司	2024-05-14
真性红细胞增多症后骨髓纤维化	临床2期	中国	成都赜灵生物医药科技有限公司	2024-05-14
原发性骨髓纤维化	临床2期	中国	成都赜灵生物医药科技有限公司	2024-05-14
蕈样真菌病	临床2期	中国	成都赜灵生物医药科技有限公司	2024-05-06
真性红细胞增多症	临床2期	中国	成都赜灵生物医药科技有限公司	-
原发性血小板增多症	临床2期	中国	成都赜灵生物医药科技有限公司	-
骨髓肿瘤	临床1期	-	成都赜灵生物医药科技有限公司	2021-11-12
移植物抗宿主病	临床前	中国	成都赜灵生物医药科技有限公司	2024-08-22
噬血细胞性淋巴组织细胞增多症	临床前	中国	成都赜灵生物医药科技有限公司	2024-03-22