Delving into the Latest Updates on Jing Medicine Technology Shanghai Ltd. with Synapse

Overview

Tags

Neoplasms

Respiratory Diseases

Immune System Diseases

Proteolysis-targeting chimeras (PROTAC)

Chemical drugs

Small molecule drug

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Neoplasms	7
Endocrinology and Metabolic Disease	1
Immune System Diseases	1

Top 5 Drug Type	Count

Proteolysis-targeting chimeras (PROTAC)	5
Chemical drugs	4
Small molecule drug	2
Monoclonal antibody	1

Top 5 Target	Count

EGFR(Epidermal growth factor receptor erbB1)	2
IL-18BP(interleukin 18 binding protein)	1
EED(Polycomb protein EED)	1
NSD3(nuclear receptor binding SET domain protein 3)	1
EGFR C797S(Epidermal Growth Factor Receptor C797S)	1

AbstractThe EGFR C797S mutation is the most common on-target resistance mechanism to osimertinib in patients with advanced non–small cell lung cancer (NSCLC). Currently there are no effective treatment options for patients with NSCLC harboring EGFR C797S triple mutants (Del19/T790M/C797S and L858R/T790M/C797S). Herein, we report an orally bioavailable EGFR PROTAC, HJM-561, which selectively degrades the EGFR C797S-containing triple mutants. HJM-561 potently inhibits the proliferation of Del19/T790M/C797S and L858R/T790M/C797S Ba/F3 cells while sparing cells expressing wild-type EGFR. Oral administration of HJM-561 shows robust antitumor activity in EGFR Del19/T790M/C797S-driven Ba/F3 CDX and PDX models that were resistant to osimertinib treatment. Taken together, our results suggest that HJM-561 is a promising therapeutic option for overcoming EGFR triple mutation-mediated drug resistance in NSCLC.Watch the interview with George Zhang, PhD, recipient of the 2024 Molecular Cancer Therapeutics Award for Outstanding Journal Article: https://vimeo.com/992990122

01 May 2021·European Journal of Medicinal ChemistryQ1 · MEDICINE

Structure-based discovery of SIAIS001 as an oral bioavailability ALK degrader constructed from Alectinib

Q1 · MEDICINE

Article

Author: Kong, Ying ; Qu, Xiaojuan ; Song, Xiaoling ; Zhong, Hui ; Liu, Haixia ; Yang, Xiaobao ; Jiang, Biao ; Sun, Ning ; Ren, Chaowei

Fusion proteins of the anaplastic lymphoma kinase (ALK) are promising therapeutic targets for cancer and other human diseases, especially for non-small cell lung cancer (NSCLC) and anaplastic large-cell lymphomas (ALCLs). We described herein a structure-based design, synthesis, and evaluation of ALK PROTACs (proteolysis-targeting chimeras) based on Alectinib as the warhead. We firstly screened CRBN ligands as the E3 ligase moiety, then obtained a series of potent ALK degraders based on different CRBN ligands, exemplified by SIAIS091 and SIAIS001 with lenalidomide/thalidomide-based linkers. Both of them induced effective ALK degradation at low nanomolar concentrations in cells, and showed much better growth inhibition effects than Alectinib. SIAIS091 or SIAIS001 also promoted cell cycle arrest in G1/S phase. Finally, SIAIS001 exhibited good oral bioavailability in Pharmacokinetics study.

100 Deals associated with Jing Medicine Technology Shanghai Ltd.

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100 Translational Medicine associated with Jing Medicine Technology Shanghai Ltd.

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Pipeline

Pipeline Snapshot as of 23 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Discovery

4

Preclinical

Phase 1 Clinical

3

1

Other

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

HJM-353 ( EED )	Neoplasms More	Phase 1
ONPR-04 ( EGFR )	Non-Small Cell Lung Cancer More	Phase 1
HJ-002-03 ( EGFR )	EGFR-mutated non-small Cell Lung Cancer More	Phase 1
HJM-561 ( EGFR C797S )	EGFR C797S Mutation Non-small Cell Lung Cancer More	Preclinical
CNSD-01	Depressive Disorder More	Preclinical