Delving into the Latest Updates on NIP-142 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

EGFR exon 20 x HER2 exon 20

Mechanism

EGFR exon 20 inhibitors(EGFR exon 20 Mutation inhibitors), HER2 exon 20 inhibitors(ERBB2 Exon 20 Mutation inhibitors)

Therapeutic Areas

NeoplasmsRespiratory Diseases

Active Indication

EGFR-mutated non-small Cell Lung CancerNon-Small Cell Lung Cancer

Inactive Indication-

Originator Organization

China Pharmaceutical Research & Development Center Co., Ltd.

Active Organization

China Pharmaceutical Research & Development Center Co., Ltd.

China Resources Pharmaceutical Group Ltd.

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure

Molecular FormulaC23H27N3O6

InChIKeyHWADWMAQVCHLHJ-MMYMAHBISA-N

CAS Registry203002-58-8

试验对象1：EGFR突变阳性的局部晚期/转移性NSCLC患者试验对象2：EGFR ex20ins的局部晚期/转移性NSCLC患者 Ia期主要目的： 1.评价NIP142胶囊在试验对象1中的安全性与耐受性。 2.探索NIP142胶囊在试验对象1中的DLT和MTD。次要目的： 1.评价NIP142胶囊及其主要代谢产物（如数据允许）在试验对象1中的PK特征。 2.初步评价NIP142胶囊在试验对象1中的ORR、DOR、DCR、PFS和OS [仅适用于EGFR ex20ins患者]。 Ib期主要目的：评价NIP142胶囊在试验对象2中的ORR。次要目的 1.确定NIP142胶囊在试验对象2中的RP2D。 2.评价NIP142胶囊在试验对象2中的DOR、DCR、PFS和OS。 3.评价NIP142胶囊在试验对象2中的安全性。 4.基于群体PK分析方法，探索NIP142胶囊在试验对象2中的PK特征（如数据允许）。

[Translation]

Subject 1: Patients with locally advanced/metastatic NSCLC who are EGFR mutation-positive Subject 2: Patients with locally advanced/metastatic NSCLC who have EGFR ex20ins Phase Ia Primary objectives: 1. Evaluate the safety and tolerability of NIP142 capsules in subject 1. 2. Explore the DLT and MTD of NIP142 capsules in subject 1. Secondary objectives: 1. Evaluate the PK characteristics of NIP142 capsules and their major metabolites (if data permit) in subject 1. 2. Preliminary evaluation of ORR, DOR, DCR, PFS and OS of NIP142 capsules in subject 1 [only for patients with EGFR ex20ins]. Phase Ib Primary objectives: Evaluate the ORR of NIP142 capsules in subject 2. Secondary objectives 1. Determine the RP2D of NIP142 capsules in subject 2. 2. Evaluate the DOR, DCR, PFS and OS of NIP142 capsules in subject 2. 3. Evaluate the safety of NIP142 capsules in trial subject 2. 4. Based on the population PK analysis method, explore the PK characteristics of NIP142 capsules in trial subject 2 (if data permit).

Start Date11 May 2022

Sponsor / Collaborator

China Pharmaceutical Research & Development Center Co., Ltd.

ChiCTR2200057107 / SuspendedPhase 1IIT

A single arm, open-label, multicenter phase Ia/Ib clinical trial to evaluate the safety, tolerance, pharmacokinetics and efficacy of NIP 142 capsule in patients with locally advanced / metastatic non-small cell lung cancer with EGFR mutation positive

Start Date22 Mar 2022

Sponsor / Collaborator

Shanghai Pulmonary Hospital

100 Clinical Results associated with NIP-142

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100 Translational Medicine associated with NIP-142

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100 Patents (Medical) associated with NIP-142

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7

Literatures (Medical) associated with NIP-142

01 Jan 2011·Biological and Pharmaceutical BulletinQ4 · MEDICINE

Blocking Effect of NIP-142 on the KCNQ1/KCNE1 Channel Current Expressed in HEK293 Cells

Q4 · MEDICINE

Article

Author: Takahashi, Tetsuo ; Namekata, Iyuki ; Tsuruoka, Noriko ; Iida-Tanaka, Naoko ; Tsuneoka, Yayoi ; Takahara, Akira ; Suzuki, Takeshi ; Tanaka, Hikaru ; Tanaka, Yoshio ; Matsuda, Tomoyuki

We examined the effect of NIP-142, a benzopyran compound with terminating effect on experimental atrial arrhythmia, on the KCNQ1/KCNE1 channel, which underlies the slow component of the cardiac delayed rectifier potassium channel (I(Ks)). NIP-142, as well as chromanol 293B, showed concentration-dependent blockade of the current expressed in HEK293 cells; the EC(50) value of NIP-142 and chromanol 293B for the inhibition of tail current was 13.2 µM and 4.9 µM, respectively. These results indicate that NIP-142 has blocking effect on the KCNQ1/KCNE1 channel current.

01 Jan 2010·Biological and Pharmaceutical BulletinQ4 · MEDICINE

Effect of NIP-142 on Potassium Channel .ALPHA.-Subunits Kv1.5, Kv4.2 and Kv4.3, and Mouse Atrial Repolarization

Q4 · MEDICINE

Article

Author: Tanaka, Yoshio ; Tanaka, Hikaru ; Masuda, Hiroyuki ; Namekata, Iyuki ; Hamaguchi, Shogo ; Iida-Tanaka, Naoko ; Kawamura, Taro ; Takahara, Akira

Effects of NIP-142, a benzopyran compound which terminates experimental atrial arrhythmia, on potassium channel alpha-subunits and mouse atrial repolarization were examined. NIP-142 concentration-dependently blocked the outward current through potassium channel alpha subunits Kv1.5, Kv4.2 and Kv4.3 expressed in Xenopus oocytes. In isolated mouse atrial myocardia, NIP-142 prolonged the action potential duration and effective refractory period, and increased the contractile force. These results suggest that NIP-142 blocks the potassium channels underlying the transient and sustained outward currents, which may contribute to its antiarrhythmic activity.

01 Dec 2009·Expert Opinion on Investigational DrugsQ2 · MEDICINE

Vernakalant hydrochloride for the treatment of atrial fibrillation

Q2 · MEDICINE

Article

Author: Dimitri P Mikhailidis ; Gregory Y H Lip ; Grzegorz Raczak ; Szymon Budrejko ; Jacek Rysz ; Dariusz Kozlowski ; Maciej Banach

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Rhythm control strategy for AF is limited by drug toxicity and side effects, and recent trials have shown that this strategy is not superior to a rate control one. New antiarrhythmic drugs, free of undesired effects, would enhance rhythm control, with the possibility of sinus rhythm restoration and maintenance. A promising find in the search for new antiarrhythmic therapies is atrial-tissue specific ion channels. The findings that the ultrarapid delayed rectifier (I(Kur)) and the inwardly rectifying, acetylcholine-regulated current (I(K-Ach)) exist in atrial but not ventricular tissue increase the probability that atrioselective drugs without ventricular proarrhythmic toxicity can be developed for treatment of patients with AF. There are also other potential targets for atrial-selective therapy: transient outward current (I(to)), rapidly and slowly activating delayed rectifier currents (I(Kr) and I(Ks)), atrial sodium current (I(Na)) and atrially expressed connexins. New drugs under development with promising atrial-selectivity include: tertiapin, NIP-142, NIP-141, JTV-519, AVE0118, AVE1231, DPO-1, AZD7009 and many others. Among such new agents, vernakalant hydrochloride is currently in an advanced phase of development and has already been evaluated in clinical trials. In this overview, we describe the history and current state of developmental process of the drug, as well as its mechanism of action and influence on electrophysiological parameters. Vernakalant seems to be effective in terminating recent-onset AF, but is not efficacious in long-lasting AF and atrial flutter. The drug may be relatively free of proarrhythmic effects, and exerts a protective effect on ventricular tissue and ventricular repolarization. It is expected that the intravenous formulation will soon be approved for the pharmacological termination of recent-onset AF.

100 Deals associated with NIP-142

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
EGFR-mutated non-small Cell Lung Cancer	Phase 1	CN	China Pharmaceutical Research & Development Center Co., Ltd.	11 May 2022
Non-Small Cell Lung Cancer	Phase 1	CN	China Resources Pharmaceutical Group Ltd.	30 Jan 2022