Delving into the Latest Updates on Tafetinib Malate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

VEGFR

Mechanism

VEGFR antagonists(Vascular endothelial growth factor receptor antagonists)

Therapeutic Areas

Neoplasms

Active Indication-

Inactive Indication

Advanced Malignant Solid Neoplasm

Originator Organization

Simcere Pharmaceutical Group Ltd.

Active Organization

Nanjing Simcere Dongyuan Pharmaceutical Co. Ltd.

Jilin Boda Pharmaceutical Co., Ltd.

Inactive Organization

Nanjing Youke Biomedical Research Co., Ltd.

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure

Molecular FormulaC28H35FN4O7

InChIKeyNPDDNEROALBBFV-FAKOYBSZSA-N

CAS Registry1581241-28-2

Tafetinib is an oral multitargeted tyrosine kinase inhibitor that inhibits Vascular Endothelial Growth Factor Receptor (VEGFR).
This phase I trial was conducted to evaluate the pharmacokinetics (PK), safety, and preliminary efficacy of tafetinib in Chinese patients with advance solid tumor. The study are conducting in Cancer Hospital Chinese Academy of Medical Sciences.

Start Date01 May 2015

Sponsor / Collaborator

Nanjing Youke Biomedical Research Co., Ltd.

100 Clinical Results associated with Tafetinib Malate

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100 Translational Medicine associated with Tafetinib Malate

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100 Patents (Medical) associated with Tafetinib Malate

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3

Literatures (Medical) associated with Tafetinib Malate

01 Jul 2013·Journal of Pharmaceutical and Biomedical AnalysisQ3 · MEDICINE

Simultaneous quantification of tafetinib (SIM010603), a novel potent inhibitor of receptor tyrosine kinase, and its major metabolite in dog plasma by HPLC–ESI/MS/MS and its application to a pharmacokinetic study

Q3 · MEDICINE

Article

Author: Feng Shao ; Xin Liu ; Tian Zhu ; Feng Tang

This study presents a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI/MS/MS) technique for the simultaneous determination of tafetinib (SIM010603) and its main metabolite (M1) in dog plasma by using Prazosin hydrochloric acid as the internal standard (IS). Both compounds were extracted from dog plasma with ethyl acetate and were separated by HPLC on a reversed phase C₁₈ column with a mobile phase of 10 mM ammonium acetate buffer containing 0.1% formic acid-acetonitrile (40:60, v/v) at a flow rate of 0.2 mL/min. For quantification, the triple-quadruple MS was used in selected reaction monitoring (SRM) mode. The monitored transitions were m/z 425.3 → 309.2 for tafetinib, m/z 397.2 → 309.2 for M1 and m/z 384.2 → 247.1 for IS. The developed method had a short run time of 4 min and good linearity was observed over a wide range of 1-1000 ng/mL for the two compounds. The method was successfully applied in the pharmacokinetic study of tafetinib and M1 in dog.

01 May 2012·Food and Chemical ToxicologyQ2 · MEDICINE

Evaluation of subchronic toxicity of SIM010603, a potent inhibitor of receptor tyrosine kinase, after 28-day repeated oral administration in SD rats and beagle dogs

Q2 · MEDICINE

Article

Author: Guocai Lu ; Zhenna Xia ; Lin Zhu ; Ying Zong ; Yu Mao ; Xiaofang Zhang ; Bojun Yuan

SIM010603, a promising multi-targeted receptor tyrosine kinase (RTK) inhibitor, is now being considered for evaluation in phase clinical trial. In this work, the subchronic toxicity of SIM010603 in SD rats and beagle dogs have been characterized. Rats and dogs received SIM010603 orally (0-20 and 0-10mg/kg/day, respectively) on a consecutive daily dosing schedule for 28 days following a 14 days recovery period. Sunitinib was used as a positive control. The No Observed Adverse Effect Level (NOAEL) of SIM010603 was 5mg/kg/day for rats, and undefined for dogs. The treatment resulted in unscheduled mortality in dogs receiving 10mg/kg of SIM010603 or Sunitinib. The adverse effects of SIM010603 on rats and dogs mainly included gastrointestinal toxicity, skeletal toxicity, myelosuppression, thymus atrophy, bronchopneumonia, cardiovascular dysfunction, and pancreatic toxicity. Similar observations have also been noted with this class of RTK signaling inhibitors and are consistent with pharmacologic perturbations of physiologic/angiogenic processes associated with the intended molecular targets. Most treatment-induced effects were reversible or showed ongoing recovery upon discontinuation of treatment. SIM010603 has shown comparable toxicity effect on beagle dogs, while better tolerability on SD rats when compared to Sunitinib.

01 Jan 2012·Cancer Chemotherapy and PharmacologyQ4 · MEDICINE

Preclinical anti-angiogenesis and anti-tumor activity of SIM010603, an oral, multi-targets receptor tyrosine kinases inhibitor

Q4 · MEDICINE

Article

Author: Zhenzhou Jiang ; Sen Wang ; Luyong Zhang ; Dongchun Wang ; Feng Tang

OBJECTIVESIM010603 is a structurally novel, oral, multi-targeted receptor tyrosine kinase inhibitor. This study investigated the anti-angiogenic and anti-tumor effects of SIM010603.METHODSA radiometric protein kinase assay was used for measuring the kinase activity of the 32 protein kinases. Receptor phosphorylation was determined by enzyme-linked immunosorbent assay (ELISA). Cell proliferation was measured by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cell chemotaxis was evaluated by modified Boyden chamber assay. Effect of SIM010603 on angiogenesis was examined by mouse cornea angiogenesis assay. Effect of SIM010603 on xenografts was assessed by tumor growth delay. Effects of SIM010603 on tumor microvascular density (MVD), recruitment of pericytes, and pericyte encapsulation of tumor vessels were analyzed by immunofluorescent staining technique.RESULTSSIM010603 inhibited stem cell factor receptor (Kit), vascular endothelial growth factor receptor-2 (VEGFR-2), platelet-derived growth factor receptor-β (PDGFR-β), glial cell line-derived neurotrophic factor receptor (Rearranged during Transfection; RET), and Fms-like tyrosine kinase-3 (FLT3) with IC(50) values between 5.0 and 68.1 nmol/l. SIM010603 inhibited the phosphorylation of PDGFR-β and VEGFR-2. Moreover, SIM010603 inhibited endothelial cell proliferation, endothelial cells chemotaxis, and corneal angiogenesis. Although SIM010603 exhibited lower activity in regard to proliferation of NCI-H460, MDA-MB-435, and T241-VEGF-A cells (IC(50) > 1 μmol/l), SIM010603 inhibited tumor growth in these xenograft tumor growth models. SIM010603 reduced tumor MVD in T241-VEGF-A tumor xenograft models and decreased positive signals of CD31, NG2 in MDA-MB-435, and LLC-SW-44 xenograft tumor models.CONCLUSIONSThese results support the clinical assessment of SIM010603 as a therapeutic agent for cancer.

100 Deals associated with Tafetinib Malate

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