Delving into the Latest Updates on Conteltinib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

首要泽

Target

ALK x FAK x IGF-1R x PYK2

Mechanism

ALK inhibitors(Anaplastic lymphoma kinase inhibitors), FAK inhibitors(Focal adhesion kinase inhibitors), IGF-1R antagonists(Insulin-like growth factor I receptor antagonists)

+ [1]

Therapeutic Areas

NeoplasmsRespiratory DiseasesDigestive System Disorders+ [1]

Active Indication

ALK positive Non-Small Cell Lung CancerPancreatic CancerHepatocellular Carcinoma

Inactive Indication-

Originator Organization

Centaurus Biopharma Co Ltd

Active Organization

Centaurus Biopharma Co Ltd

Shouyao Holdings (Beijing) Co. Ltd.

Zhejiang University

+ [1]

Inactive Organization-

Drug Highest PhaseNDA/BLA

First Approval Date-

Regulation-

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Structure

Molecular FormulaC32H45N9O3S

InChIKeyNPJCURIANJMFEO-UHFFFAOYSA-N

CAS Registry1384860-29-0

第一部分：伊曲康唑对CT-707颗粒在健康受试者中的药代动力学影响研究主要目的：评价伊曲康唑对CT-707颗粒在健康受试者中的药代动力学影响；次要目的：评价CT-707片和CYP3A4强抑制剂伊曲康唑合用在健康受试者中的安全性和耐受性；第二部分：利福平对CT-707颗粒在健康受试者中的药代动力学影响研究主要目的：评价利福平对CT-707颗粒在健康受试者中的药代动力学影响；次要目的：评价CT-707片和CYP3A4强诱导剂利福平合用在健康受试者中的安全性和耐受性。

[Translation]

Part I: Study on the pharmacokinetics of CT-707 granules in healthy subjects Main purpose: To evaluate the pharmacokinetics of CT-707 granules in healthy subjects; Secondary purpose: To evaluate the safety and tolerability of CT-707 tablets and itraconazole, a strong CYP3A4 inhibitor, in healthy subjects; Part II: Study on the pharmacokinetics of CT-707 granules in healthy subjects Main purpose: To evaluate the pharmacokinetics of CT-707 granules in healthy subjects; Secondary purpose: To evaluate the safety and tolerability of CT-707 tablets and rifampicin, a strong CYP3A4 inducer, in healthy subjects.

Start Date28 Jul 2021

Sponsor / Collaborator

Centaurus Biopharma Co Ltd

100 Clinical Results associated with Conteltinib

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100 Translational Medicine associated with Conteltinib

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100 Patents (Medical) associated with Conteltinib

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9

Literatures (Medical) associated with Conteltinib

01 Dec 2022·BMC CancerQ2 · MEDICINE

CT-707 overcomes hypoxia-mediated sorafenib resistance in Hepatocellular carcinoma by inhibiting YAP signaling

Q2 · MEDICINE

ArticleOA

Author: Yuan, Tao ; Zhang, Bo ; Lin, Nengmin ; He, Qiaojun ; Ye, Song ; Chen, Zibo ; Yan, Fangjie ; Zhu, Hong ; Xie, Qin ; Yang, Bo

AbstractBackgroundHepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Sorafenib is the first-line treatment for advanced HCC, but the anti-cancer effects remain to be improved as indicated by its low response rates and failure to prolong the progression-free survival (PFS). Thus, it is urgent to explore approaches to improve the clinical outcome.Materials and methodsThe effect of Sorafenib in HCC was analyzed by SRB (sulforhodamine B) assay in normoxia and hypoxia, respectively. The different dose combination effect of CT707 and sorafenib was analyzed by SRB assay in hypoxia. Flow cytometry assay was used to detect the cell apoptosis rate with CT707 and sorafenib treatment in hypoxia. Western blotting was used to detect the expression levels of apoptosis -related proteins and the mechanism of CT707 overcome the resistance of sorafenib in hypoxia.ResultsOur study showed that the characteristic intratumor hypoxia of advanced HCC is one of the major factors which mediated the drug resistance towards sorafenib in HCC. And CT-707, a novel multi-kinase inhibitor, could sensitize the hypoxic HCC cells towards sorafenib. Further studies showed that CT-707 abolished the nuclear translocation of Yes Associate-Protein (YAP), which has been demonstrated as one of mechanism of hypoxia-mediated sorafenib-resistance in HCC.ConclusionsOverall, this study not only favors the development of this novel multi-kinase inhibitor CT-707 as a therapeutic agent against HCC, but also provides a potential strategy to overcome the hypoxia-mediated resistance to sorafenib in HCC patients.

01 Feb 2022·Acta Biochimica et Biophysica SinicaQ2 · BIOLOGY

SY-707, an ALK/FAK/IGF1R inhibitor, suppresses growth and metastasis of breast cancer cells

Q2 · BIOLOGY

Article

Author: Liu, Ping ; Liu, Xijie ; Chu, Qiaoyun ; Liu, Shuang ; Niu, Jing ; Sun, Yinghui

Focal adhesion kinase (FAK), a multi-functional cytoplasmic tyrosine kinase, plays a critical role in cancer migration, proliferation and metastasis via regulating multiple signaling pathways. SY-707 is an anaplastic lymphoma kinase (ALK)/FAK/type 1 insulin-like growth factor receptor (IGF1R) multi-kinase inhibitor which is now being evaluated in phase II clinical trials for ALK positive non-small cell lung cancer (NSCLC). However, the effect of SY-707 on breast cancer is unknown. In this study, we assessed preclinical the anti-growth and anti-metastasis potency of SY-707 in breast cancer cells. ATP content, PE-Annexin V, and would healing assays were used to examine cell proliferation, cell cycle and migration. Then, SD rat and beagle dog models were used to evaluate the pharmacokinetics profile of SY-707, and mouse xenograft model was used to evaluate the anti-cancer activities of SY-707 . We found that breast cancer cells apoptosis were induced by SY-707. Moreover, SY-707 exerted inhibition on cell migration and adhesion in a dose-dependent manner. In T47D xenograft mice, SY-707 had significant anti-tumor activities alone or synergistically with Paclitaxel. Meanwhile, SY-707 also displayed significant suppression on spontaneous metastasis of tumor to the lung in 4T1 murine breast cancer xenograft model. In conclusion, SY-707 has potent anti-proliferation and anti-migration potential in breast cancer and , implying its therapeutic application for the treatment of breast cancer in future clinical trials.

01 May 2020·Thoracic CancerQ3 · MEDICINE

Single‐center study to determine the safety and efficacy of CT‐707 in Chinese patients with advanced anaplastic lymphoma kinase‐rearranged non‐small‐cell lung cancer

Q3 · MEDICINE

ArticleOA

Author: Yang, Dongliang ; Si, Xiaoyan ; Zhang, Xiaotong ; Wang, Hanping ; Song, Peng ; Zhang, Li

IntroductionIt has been proven that ALK‐rearranged non‐small cell lung cancer (NSCLC) is sensitive to ALK inhibitors while the chemotherapy resistance is unavoidable. In this study, safety and antitumor activity of the novel ALK inhibitor (ALKi) CT‐707 were evaluated in Chinese patients with advanced ALK‐rearranged NSCLC.MethodsThis single‐center, open‐label phase I study recruited adult patients with ALK‐rearrangement (confirmed by fluorescence in situ hybridization and/or immunohistochemistry) of locally advanced/metastatic malignancies including NSCLC. This study consisted of two parts: dose escalation and dose expansion. CT‐707 was administered orally once a day for 21 days.ResultsA total of 13 patients who were treated with CT‐707 from 450 to 600 mg (in the dose increasing phase) were enrolled in this trial (two patients were previously treated with crizotinib). There were 12 patients diagnosed with lung adenocarcinoma and one patient with malignant pleural mesothelioma. After treatment, grade 3 diarrhea (600 mg once a day) was found as dose‐limiting toxicity (DLT).The most common adverse events included diarrhea (92%), elevated aspartate aminotransferase (61%), elevated alanine aminotransferase (54%), hair loss (38%), and vomiting (31%). The overall response rate was 77% (10/13). Among all patients, four of the five patients who did not receive any treatment, one of the two patients who had received treatments with crizotinib, and five of the six patients who received standard chemotherapy achieved partial response (PR). One patient reached a complete remission (CR).ConclusionsThis study indicated that CT‐707 is clinically effective as a new antitumor drug for Chinese lung adenocarcinoma patients with ALK rearrangement. It is safe and reliable and the dose‐expansion phase recruitment has started.

100 Deals associated with Conteltinib

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
ALK positive Non-Small Cell Lung Cancer	NDA/BLA	CN	Shouyao Holdings (Beijing) Co. Ltd.	23 Oct 2024
ALK positive Non-Small Cell Lung Cancer	NDA/BLA	CN	Beijing SL Pharmaceutical Co., Ltd.	23 Oct 2024
Pancreatic Cancer	Phase 2	CN	Shouyao Holdings (Beijing) Co. Ltd.	11 Aug 2022
Hepatocellular Carcinoma	Preclinical	CN	Zhejiang University	01 Dec 2016
Hepatocellular Carcinoma	Preclinical	CN	Centaurus Biopharma Co Ltd	01 Dec 2016

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02695550 (Pubmed) Manual	Phase 1	ALK positive Non-Small Cell Lung Cancer	60	Conteltinib (ALK TKI-naïve)	(xefaryygqd) = MTD was not reached ysdrlvajfr (jpghlpbokw ) View more	Positive	23 Nov 2022
NCT02695550 (Pubmed) Manual	Phase 1	ALK positive Non-Small Cell Lung Cancer	60	Conteltinib (received crizotinib previously)		Positive	23 Nov 2022
NCT02695550 (ESMO_ASIA2019) Manual	Phase 1	Neoplasms \| ALK positive Non-Small Cell Lung Cancer ALK Rearrangement	13	CT-707	(kknyondkad) = diarrhea 92%, elevated aspartate aminotransferase 61%, elevated alanine aminotransferase 54%, hair loss 38%, vomiting 31% fqonytprjo (zvjvkhzxxk ) View more	Positive	23 Nov 2019
NCT02695550 (ESMO_ASIA2017) Manual	Phase 1	ALK positive Non-Small Cell Lung Cancer ALK Positive	23	Conteltinib	(ovegpdfmot) = none tlejldhvuu (awlnwqjzpr ) View more	Positive	18 Nov 2017