Delving into the Latest Updates on Simotinib Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Simotinib, Ximotini

+ [1]

Target

EGFR

Mechanism

EGFR antagonists(Epidermal growth factor receptor erbB1 antagonists)

Therapeutic Areas

NeoplasmsDigestive System DisordersRespiratory Diseases+ [1]

Active Indication

Non-Small Cell Lung CancerBreast CancerColonic Cancer

Inactive Indication-

Originator Organization

Simcere Pharmaceutical Group Ltd.

Active Organization

Simcere Pharmaceutical Group Ltd.

Advenchen Laboratories LLC

Nanjing Simcere Dongyuan Pharmaceutical Co. Ltd.

Inactive Organization

Jiangsu Simcere Pharmaceutical Co., Ltd.

Drug Highest PhasePhase 1

First Approval Date-

RegulationSpecial Review Project (CN)

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Structure

Molecular FormulaC25H26ClFN4O4

InChIKeyOXWUWXCJDBRCCG-UHFFFAOYSA-N

CAS Registry944258-89-3

View All Structures (2)

To observe the safety and tolerability of simotinib hydrochloride tablets in patients with advanced NSCLC, determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of the drug in humans; reveal the pharmacokinetic characteristics of simotinib hydrochloride tablets; and preliminarily observe the effectiveness and effective dose of simotinib hydrochloride tablets.

Start Date15 Apr 2013

Sponsor / Collaborator

Jiangsu Simcere Pharmaceutical R&D Co., Ltd.

[+1]

NCT01772732 / Unknown statusPhase 1

Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of Simotinib Hydrochloride in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

The primary objective is to assess the safety and tolerability of multiple doses of Simotinib Hydrochloride in NSCLC patients. The secondary objective is to determine the pharmacokinetic (PK) profile and explore the preliminary anti-tumor activity.

Start Date01 Dec 2012

Sponsor / Collaborator

Jiangsu Simcere Pharmaceutical Co., Ltd.

NCT01469910 / CompletedPhase 1

Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of Simotinib Hydrochloride in Healthy Subjects

The purpose of this study is to assess the safety and pharmacokinetics of single ascending doses of Simotinib Hydrochloride in healthy subjects.

Start Date01 Sep 2011

Sponsor / Collaborator

Jiangsu Simcere Pharmaceutical Co., Ltd.

100 Clinical Results associated with Simotinib Hydrochloride

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100 Translational Medicine associated with Simotinib Hydrochloride

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100 Patents (Medical) associated with Simotinib Hydrochloride

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5

Literatures (Medical) associated with Simotinib Hydrochloride

01 Apr 2016·Anti-Cancer DrugsQ4 · MEDICINE

Simotinib as a modulator of P-glycoprotein

Q4 · MEDICINE

Article

Author: Chen, Yanfen ; Zhu, Qubo ; Huang, Lingling ; Shen, Cheng ; Cheng, Zeneng ; Yan, Huiwen

As a new antitumor drug, simotinib hydrochloride is prescribed for prolonged periods, often to patients with comorbidities. Therefore, the risk for developing drug resistance and drug-drug interactions between simotinib and other agents has to be taken into consideration. As P-glycoprotein (P-gp) is an efflux transporter, which plays a significant role in drug resistance and influences the pharmacological properties and toxicities of the drugs it interacts with, the interactions between simotinib and P-gp were investigated. Cytotoxicity was measured using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Intracellular drug concentrations were detected by high-performance liquid chromatography, fluorescence-activated cell sorting and using a fluorescence reader. P-gp ATPase activity was measured using the Pgp-Glo assay, and intracellular pH was assessed using the fluorescent probe 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl. The expression and transcription of P-gp were detected by western blotting and the luciferase assay. Simotinib has no cross-resistance to P-gp substrates, and its efflux rate was independent of either the P-gp expression or the coadministered P-gp substrate. Simotinib reversed chemotherapeutic agent resistance in a short time by increasing the intracellular concentration of the chemotherapeutic agent and blocked rhodamine 123 efflux. Further studies demonstrated that simotinib inhibited P-gp activity by modulating its ATPase activity and the intracellular pH. Although simotinib induced P-gp expression after extended treatment, the induced expression of P-gp had little impact on drug resistance. Simotinib is not a substrate of P-gp. As a modulator, it functions mainly as an inhibitor of P-gp by modulating the intracellular pH and ATPase activity, although it also induces P-gp expression after extended treatment.

01 Feb 2014·Journal of Chromatography BQ3 · MEDICINE

LC-ESI-MS/MS determination of simotinib, a novel epidermal growth factor receptor tyrosine kinase inhibitor: Application to a pharmacokinetic study

Q3 · MEDICINE

Article

Author: Cheng, Zeneng ; Liu, Xingling ; Yu, Peng ; Li, Sanwang ; He, Lihua ; Xie, Feifan ; Ran, Liling

Simotinib is a novel epidermal growth factor receptor tyrosine kinase inhibitor. This study presented a sensitive and specific liquid chromatography-electrospray ionization-mass spectrometry method using erlotinib as internal standard for the determination of simotinib in human plasma. The method involved a simple liquid-liquid extraction using diethyl ether. The analytes were separated with isocratic gradient elution on an Agilent TC-C18 column (4.6 × 150 mm, 5 μm). Mass spectrometric detector equipped with electrospray ionization source was carried out in the mode of multiple reaction monitoring (MRM). The monitored transitions were m/z 501.2→182.1 for simotinib and m/z 394.4→278.1 for erlotinib. The calibration curve of simotinib was established over the range of 2.058-3000 μg L(-1) (r(2)=0.9924). The intra- and inter-day precisions were all less than 10%, and all the biases were not more than 7%. This validated method was then successfully applied to a pharmacokinetic study involving twelve healthy Chinese volunteers. The mean Cmax and Tmax for simotinib were 254.79±98.30 μg L(-1) and 1.71±0.48 h, respectively. Plasma concentrations declined with a t1/2 of 5.37±2.32 h. AUC0-t and AUC0→∞ values obtained were 1262.59±501.41 μg L(-1) h and 1329.95±517.42 μg L(-1) h, respectively.

01 Feb 2014·Analytical and Bioanalytical ChemistryQ2 · CHEMISTRY

Development and validation of a UPLC–MS/MS assay for the quantification of simotinib in human plasma

Q2 · CHEMISTRY

Article

Author: Ping Du ; Yuankai Shi ; Xiaohong Han ; Sheng Yang ; Yuanyuan Song ; Xingsheng Hu ; Ning Li

Simotinib is a novel oral small-molecule tyrosine kinase inhibitor that has demonstrated equal or superior antineoplastic activities to erlotinib in preclinical studies. In support of a clinical pharmacokinetic study, a sensitive and accurate liquid chromatography (LC) method with mass spectrometry detection using multiple reaction monitoring (MRM) in positive ion mode was developed and validated for the quantification of simotinib in human plasma. The sample preparation procedure involved a simple protein precipitation with methanol. Erlotinib was used as the internal standard. The optimal chromatographic behavior was achieved on a Zorbax SB-C8 column (2.1 mm × 100 mm, 3.5 μm) using a mixture of 0.1% formic acid with 10 mM ammonium formate/methanol (20:80, v/v) as the mobile phase. The total LC analysis time per injection was 4 min with a flow rate of 0.2 mL/min. The recovery was greater than 90% and no significant matrix effect was observed. The assay was validated over the concentration range of 1-1,000 ng/mL. The intra- and interday precision and accuracy of the quality control samples at low, medium, and high concentration levels showed at most 9.4% relative standard deviation (RSD) and -7.4 to 7.4% relative errors (RE). Assay selectivity, freeze/thaw stability, storage stability, and dilution effects were also assessed. The method is now used to support clinical pharmacokinetic studies in patients with non-small cell lung cancer (NSCLC) after oral administration of simotinib.

100 Deals associated with Simotinib Hydrochloride

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Non-Small Cell Lung Cancer	Phase 1	CN	Nanjing Simcere Dongyuan Pharmaceutical Co. Ltd.	15 Apr 2013
Breast Cancer	Phase 1	CN	Simcere Pharmaceutical Group Ltd.	-
Breast Cancer	Phase 1	-	Advenchen Laboratories LLC	-
Colonic Cancer	Phase 1	-	Advenchen Laboratories LLC	-
Colonic Cancer	Phase 1	CN	Simcere Pharmaceutical Group Ltd.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01772732 (Pubmed \| Cancer Manag Res) Manual	Phase 1	EGFR-mutated non-small Cell Lung Cancer EGFR Mutation	41	simotinib	(oipqzmxzcm) = umezkgwego cjxxdqzmbb (lgtamfcyyc ) View more	Positive	13 May 2019
NCT01772732 (ASCO2017)	Phase 1	Advanced Lung Non-Small Cell Carcinoma First line	41	Simotinib	(rqcehanpwo) = Simotinib was well tolerated, with encouraging efficacy observed in NSCLC patients with EGFR sensitive mutations, particularly in those with BM ybupjgbjee (ssvyquvubn )	-	30 May 2017