Delving into the Latest Updates on ASLAN-002 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

MST1R x c-Met

Action

inhibitors

Mechanism

MST1R inhibitors(Macrophage-stimulating protein receptor inhibitors), c-Met inhibitors(Hepatocyte growth factor receptor inhibitors)

Therapeutic Areas

NeoplasmsDigestive System DisordersSkin and Musculoskeletal Diseases

Active Indication

Breast CancerStomach Cancer

Inactive Indication

Advanced Malignant Solid NeoplasmHead and Neck NeoplasmsMalignant Solid Neoplasm+ [4]

Originator Organization

Bristol Myers Squibb Co.

Active Organization

Bristol Myers Squibb Co.Aslan Pharmaceuticals Ltd.

Inactive Organization-

License Organization

Bristol Myers Squibb Co.Aslan Pharmaceuticals Ltd.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC25H19ClF2N4O4

InChIKeyVNBRGSXVFBYQNN-UHFFFAOYSA-N

CAS Registry1025720-94-8

There is a great need for new therapies for carcinomas that have progressed on or not responded to current therapy. There are no approved Met targeted agents in standard clinical use. In the population of subjects with advanced carcinomas that are unresponsive to standard of care, and based on the relatively safe, reversible and monitorable toxicity profile of ASLAN002 in non clinical studies, the potential for benefit from ASLAN002 outweighs the potential risks for toxicity.
The purpose of this study is to identify the maximum tolerated dose of ASLAN002 in subjects with advanced or metastatic solid tumours, as well as to define the overall safety profile of ASLAN002.

Start Date01 Oct 2012

Sponsor / Collaborator

Aslan Pharmaceuticals Ltd.

NCT00605618

/ CompletedPhase 1/2

A Phase I/II Multiple Ascending Dose Study of BMS-777607 in Subjects With Advanced or Metastatic Solid Tumors

Part A: The purpose of this study is to find the maximum tolerated dose of BMS-777607 in subjects with advanced or metastatic solid tumors
Part B: The purpose of this study is to describe the preliminary activity of BMS-77607 in subjects with advanced or metastatic gastroesophageal cancer, hormone refractory prostate cancer, head and neck squamous cell carcinoma, and type I papillary renal cell carcinoma

Start Date01 Mar 2008

Sponsor / Collaborator

Bristol Myers Squibb Co.

100 Clinical Results associated with ASLAN-002

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100 Translational Medicine associated with ASLAN-002

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100 Patents (Medical) associated with ASLAN-002

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92

Literatures (Medical) associated with ASLAN-002

01 Mar 2025·Bioorganic Chemistry

Identification of a 7H-pyrrolo[2,3-d]pyrimidin derivatives as selective type II c-Met/Axl inhibitors with potent antitumor efficacy

Article

Author: Ni, Hengfan ; Tang, Minghai ; Yang, Tao ; Xie, Lixin ; Qin, Songhui

In this study, we reported the discovery of a novel type II c-Met/Axl inhibitor, characterized by using 4-amino-7H-pyrrolo[2,3-d]pyrimidine as a hinge region binder. Through a systematic exploration of the structure-activity relationship, based on the clinically reported c-Met inhibitor BMS-777607, we identified the optimized compound 22a. 22a exhibited remarkable potency against c-Met and Axl kinases, with IC₅₀ values of 1 nM and 10 nM, respectively, and demonstrated over 100-fold selectivity to other members of the TAM subfamily. Furthermore, compared to cabozantinib, compound 22a displayed superior anti-tumor proliferation activity across a range of solid tumors. 22a demonstrated excellent drug-like properties, achieving a bioavailability of 174.2 % in rats. In established MKN-45 and HCT116 xenograft tumor models, compound 22a achieved tumor growth inhibition (TGI) rates of 98.2 % and 87.2 %, respectively, at a dosage of 1 mg/kg. Taken together, compound 22a is a selective dual c-Met/Axl inhibitor with significant potential as a clinical candidate.

01 Oct 2024·Cancer Science

Initial AXL and MCL‐1 inhibition contributes to abolishing lazertinib tolerance in EGFR‐mutant lung cancer cells

Article

Author: Ishida, Masaki ; Kawachi, Hayato ; Hirai, Soichi ; Morimoto, Kenji ; Nakamura, Ryota ; Iwasaku, Masahiro ; Nishioka, Naoya ; Sakai, Toshiyuki ; Katayama, Yuki ; Tachibana, Yusuke ; Horinaka, Mano ; Yamada, Tadaaki ; Takayama, Koichi ; Sawada, Ryo ; Matsui, Yohei ; Tokuda, Shinsaku

AbstractLazertinib, a novel third‐generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI), demonstrates marked efficacy in EGFR‐mutant lung cancer. However, resistance commonly develops, prompting consideration of therapeutic strategies to overcome initial drug resistance mechanisms. This study aimed to elucidate the adaptive resistance to lazertinib and advocate novel combination treatments that demonstrate efficacy in preventing resistance as a first‐line treatment for EGFR mutation‐positive NSCLC. We found that AXL knockdown significantly inhibited lung cancer cell viability in the presence of lazertinib, indicating that AXL activation contributes to lazertinib resistance. However, long‐term culture with a combination of lazertinib and AXL inhibitors led to residual cell proliferation and increased the MCL‐1 expression level, which was mediated by the nuclear translocation of the transcription factor YAP. Triple therapy with an MCL‐1 or YAP inhibitor in combination with lazertinib and an AXL inhibitor significantly reduced cell viability and increased the apoptosis rate. These results demonstrate that AXL and YAP/MCL‐1 signals contribute to adaptive lazertinib resistance in EGFR‐mutant lung cancer cells, suggesting that the initial dual inhibition of AXL and YAP/MCL‐1 might be a highly effective strategy in eliminating lazertinib‐resistant cells.

01 Aug 2024·Cancer Research Communications

Coordinated Targeting of S6K1/2 and AXL Disrupts Pyrimidine Biosynthesis in PTEN-Deficient Glioblastoma

Article

Author: Von Handorf, Kate M ; Sengupta, Soma ; Plas, David R. ; Wetzel, Collin ; Andreani, Cristina ; Kendler, Ady ; Sarkaria, Jann N. ; Clark, Nicholas A ; Qi, Xiaoyang ; Sarma, Pranjal ; Clark, Nicholas A. ; Ennis, Kelli N. ; Behrmann, Catherine A. ; Meller, Jarek ; Medvedovic, Mario ; Sarkaria, Jann N ; Von Handorf, Kate M. ; Behrmann, Catherine A ; Scaglioni, Pier Paolo ; Dasgupta, Biplab ; Plas, David R ; Ennis, Kelli N ; Czyzyk-Krzeska, Maria F. ; Vallabhapurapu, Subrahmanya ; Reigle, James ; Czyzyk-Krzeska, Maria F

AbstractIntrinsic resistance to targeted therapeutics in PTEN-deficient glioblastoma (GBM) is mediated by redundant signaling networks that sustain critical metabolic functions. Here, we demonstrate that coordinated inhibition of the ribosomal protein S6 kinase 1 (S6K1) and the receptor tyrosine kinase AXL using LY-2584702 and BMS-777607 can overcome network redundancy to reduce GBM tumor growth. This combination of S6K1 and AXL inhibition suppressed glucose flux to pyrimidine biosynthesis. Genetic inactivation studies to map the signaling network indicated that both S6K1 and S6K2 transmit growth signals in PTEN-deficient GBM. Kinome-wide ATP binding analysis in inhibitor-treated cells revealed that LY-2584702 directly inhibited S6K1, and substrate phosphorylation studies showed that BMS-777607 inactivation of upstream AXL collaborated to reduce S6K2-mediated signal transduction. Thus, combination targeting of S6K1 and AXL provides a kinase-directed therapeutic approach that circumvents signal transduction redundancy to interrupt metabolic function and reduce growth of PTEN-deficient GBM.Significance:Therapy for glioblastoma would be advanced by incorporating molecularly targeted kinase-directed agents, similar to standard of care strategies in other tumor types. Here, we identify a kinase targeting approach to inhibit the metabolism and growth of glioblastoma.

100 Deals associated with ASLAN-002

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12064

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Breast Cancer	Phase 2	-	Aslan Pharmaceuticals Ltd.	-
Breast Cancer	Phase 2	-	Bristol Myers Squibb Co.	-
Stomach Cancer	Phase 2	-	Aslan Pharmaceuticals Ltd.	-
Head and Neck Neoplasms	Preclinical	Australia	Bristol Myers Squibb Co.	-
Osteoporosis	Preclinical	United States	-	-
Prostatic Cancer	Preclinical	Australia	Bristol Myers Squibb Co.	-
Renal Cell Carcinoma	Preclinical	Australia	Bristol Myers Squibb Co.	-
Stomach Cancer	Preclinical	Australia	Bristol Myers Squibb Co.	-
Metastatic Solid Tumor	Discovery	-	Aslan Pharmaceuticals Ltd.	01 Oct 2012
Advanced Malignant Solid Neoplasm	Discovery	Australia	Bristol Myers Squibb Co.	01 Mar 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01721148 (Pubmed \| Invest New Drugs) Manual	Phase 1	Solid tumor	40	ASLAN002	(ghfbqabchz) = wqggiklbis euyhknnhcx (dncefqqzfz ) View more	Positive	01 Oct 2018