Delving into the Latest Updates on SPH-5030 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

HER2

Mechanism

HER2 antagonists(Receptor protein-tyrosine kinase erbB-2 antagonists)

Therapeutic Areas

NeoplasmsDigestive System Disorders

Active Indication

HER2 positive Biliary Tract NeoplasmsHER2 Positive Colorectal CancerAdvanced Malignant Solid Neoplasm+ [1]

Inactive Indication-

Originator Organization-

Active Organization

Shanghai Pharmaceuticals Holding Co., Ltd.SPH (Benxi) North Pharmaceutical Co., Ltd.

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Human epidermal growth factor receptor 2 (HER2) is a transmembrane receptor-like protein with tyrosine kinase activity that plays a vital role in processes such as cell proliferation, differentiation, and angiogenesis. The degree of malignancy of different cancers, notably breast cancer, is strongly associated with HER2 amplification, overexpression, and mutation. Currently, widely used clinical HER2 tyrosine kinase inhibitors (TKIs), such as lapatinib and neratinib, have several drawbacks, including susceptibility to drug resistance caused by HER2 mutations and adverse effects from insufficient HER2 selectivity. To address these issues, it is essential to create innovative HER2 TKIs with enhanced safety, effectiveness against mutations, and high selectivity. Typically, SPH5030 has advanced to phase I clinical trials for its strong suppression of four HER2 mutations. This review discusses the latest research progress in HER2 TKIs, with a focus on the structural optimization process and structure-activity relationship analysis. In particular, this study highlights promising design strategies to address these challenges, providing insightful information and inspiration for future development in this field.

14 Apr 2022·Journal of Medicinal ChemistryQ1 · MEDICINE

Discovery of SPH5030, a Selective, Potent, and Irreversible Tyrosine Kinase Inhibitor for HER2-Amplified and HER2-Mutant Cancer Treatment

Q1 · MEDICINE

Article

Author: Ke, Ying ; Hong, Yuan ; Chen, Na ; Qian, Hai ; Wang, Qian ; Tu, Yuanxiang ; Xu, Jia ; Jin, Kaijun ; Gong, Wanchun ; Wang, Xuenan ; Zuo, Hongjian ; Zhang, Jing ; Duan, Lingjun ; Zhang, Zhihui ; Xia, Guangxin ; Li, Di

Small-molecule irreversible tyrosine kinase inhibitors as high potent agents have led to improvements in disease-free and overall survival in patients with HER2-amplified cancer. The approved irreversible HER2 inhibitors, neratinib and pyrotinib, both lack HER2 selectivity, leading to off-target adverse events in patients. The development of HER2 mutation during treatment also hampers the progress of the treatment. We used a molecular hybridization strategy for structural optimizations, in conjunction with in vitro and in vivo drug-like property screening, to obtain a clinical candidate SPH5030. Overall, SPH5030 showed excellent activities against four frequent kinds of HER2 mutants and high relative HER2 selectivity compared with neratinib and pyrotinib, good pharmacokinetic characteristics with desirable bioavailabilities, and significant in vivo antitumor efficacy in xenograft mouse models, especially in a HER2 mutation A775_G776insYVMA xenograft mouse model with its potency much higher than those of neratinib and pyrotinib.

100 Deals associated with SPH-5030

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
HER2 positive Biliary Tract Neoplasms	Phase 2	CN	Shanghai Pharmaceuticals Holding Co., Ltd.	11 Jul 2024
HER2 Positive Colorectal Cancer	Phase 2	CN	Shanghai Pharmaceuticals Holding Co., Ltd.	11 Jul 2024
Advanced Malignant Solid Neoplasm	Phase 1	CN	Shanghai Pharmaceuticals Holding Co., Ltd.	04 Mar 2024
HER2 Positive Solid Tumors	Phase 1	CN	Shanghai Pharmaceuticals Holding Co., Ltd.	28 Dec 2021
HER2 Positive Solid Tumors	Phase 1	CN	SPH (Benxi) North Pharmaceutical Co., Ltd.	28 Dec 2021

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05245058 (Phase 1a study of SPH5030, ASCO2024)	Phase 1	HER2 Positive Solid Tumors HER2 positive	30	SPH5030 50mg	(gcqgzpbfmr) = 20.0%, 0% ≥ G3 wsejlhrsdg (mxyfezdvas ) View more	Positive	24 May 2024
				SPH5030 100mg