Delving into the Latest Updates on Flunotinib maleate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Flonoltinib Maleate

Target

CDK6 x FLT3 x JAK2

Mechanism

CDK6 inhibitors(Cyclin-dependent kinase 6 inhibitors), FLT3 inhibitors(Tyrosine-protein kinase receptor FLT3 inhibitors), JAK2 inhibitors(Tyrosine-protein kinase JAK2 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [1]

Active Indication

Post-essential thrombocythemia myelofibrosisPost-polycythemia vera myelofibrosisPrimary Myelofibrosis+ [5]

Inactive Indication-

Originator Organization

Chengdu Zeling Biomedical Technology Co. Ltd.

Active Organization

Chengdu Zeling Biomedical Technology Co. Ltd.

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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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)

Start Date06 May 2024

Sponsor / Collaborator

Chengdu Zeling Biomedical Technology Co. Ltd.

ChiCTR2400081717 / RecruitingPhase 1IIT

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.

Start Date13 Mar 2024

Sponsor / Collaborator-

NCT06387966 / RecruitingPhase 1

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

Start Date29 Feb 2024

Sponsor / Collaborator

Chengdu Zeling Biomedical Technology Co. Ltd.

100 Clinical Results associated with Flunotinib maleate

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100 Translational Medicine associated with Flunotinib maleate

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100 Patents (Medical) associated with Flunotinib maleate

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6

Literatures (Medical) associated with Flunotinib maleate

01 Apr 2024·Journal of Pharmaceutical and Biomedical Analysis

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

Article

Author: 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.

03 Oct 2023·Expert Opinion on Investigational Drugs

Novel Janus-kinase (JAK) Inhibitors in Myelofibrosis

Review

Author: 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.

01 May 2023·Journal of Chromatography B

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

Article

Author: 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 Deals associated with Flunotinib maleate

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Post-essential thrombocythemia myelofibrosis	Phase 2	CN	Chengdu Zeling Biomedical Technology Co. Ltd.	14 May 2024
Post-polycythemia vera myelofibrosis	Phase 2	CN	Chengdu Zeling Biomedical Technology Co. Ltd.	14 May 2024
Primary Myelofibrosis	Phase 2	CN	Chengdu Zeling Biomedical Technology Co. Ltd.	14 May 2024
Mycosis Fungoides	Phase 2	CN	Chengdu Zeling Biomedical Technology Co. Ltd.	06 May 2024
Polycythemia Vera	Phase 2	CN	Chengdu Zeling Biomedical Technology Co. Ltd.	-
Thrombocythemia, Essential	Phase 2	CN	Chengdu Zeling Biomedical Technology Co. Ltd.	-
Bone Marrow Neoplasms	Phase 1	-	Chengdu Zeling Biomedical Technology Co. Ltd.	12 Nov 2021
Graft vs Host Disease	Preclinical	CN	Chengdu Zeling Biomedical Technology Co. Ltd.	22 Aug 2024
Lymphohistiocytosis, Hemophagocytic	Preclinical	CN	Chengdu Zeling Biomedical Technology Co. Ltd.	22 Mar 2024