Delving into the Latest Updates on ASLAN-002 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

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-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

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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48

Literatures (Medical) associated with ASLAN-002

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

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.

26 Sep 2023·ACS nano

Efferocytosis Nanoinhibitors to Promote Secondary Necrosis and Potentiate the Immunogenicity of Conventional Cancer Therapies for Improved Therapeutic Benefits.

Article

Author: Zhu, Yujie ; Liu, Nanhui ; Hao, Yu ; Liu, Zhuang ; Chen, Minming ; Dong, Ziliang ; Wang, Chunjie ; Wu, Yumin ; Yan, Yifan ; Liu, Bo ; Feng, Liangzhu

Efferocytosis of apoptotic cancer cells by tumor-associated macrophages or other phagocytes is reported to promote tumor immunosuppression by preventing them from secondary necrosis, which would lead to the release of intracellular components and thus enhanced immunogenicity. Therefore, current apoptosis-inducing cancer treatments (e.g., chemotherapy and radiotherapy) are less satisfactory in eliciting antitumor immunity. Herein, a nanoparticulate inhibitor of efferocytosis is prepared by encapsulating BMS777607, a hydrophobic inhibitor of receptors in macrophages responsible for phosphatidylserine-dependent efferocytosis, with biocompatible poly(lactic-co-glycolic acid) and its amphiphilic derivatives. The yielded nano-BMS can inhibit the efferocytosis of apoptotic cancer cells, thus redirecting them to immunogenic secondary necrosis. As a result, intratumorally injected nano-BMS is capable of activating both innate and adaptive antitumor immunity to achieve greatly improved therapeutic responses, when synergized with nonimmunogenic chemotherapy by cisplatin, immunogenic chemotherapy by oxaliplatin, or radiotherapy by external beams. Moreover, we further demonstrate that the inhalation of nano-BMS could significantly promote the efficacy of cisplatin chemotherapy to suppress tumor lung metastases. Therefore, this study highlights a general strategy to potentiate the immunogenicity of different cancer treatments by suppressing efferocytosis-propelled tumor immunosuppression, showing tremendous clinical potential in rescuing existing cancer therapies for more effective treatment.

01 Sep 2023·European Journal of Medicinal Chemistry

Design, synthesis and biological evaluation of 4-(4-aminophenoxy)picolinamide derivatives as potential antitumor agents

Article

Author: Zheng, Pengwu ; Zhang, Jianqing ; Chen, Ting ; Zhang, Han ; Tang, Qidong ; Dai, Jintian ; Tang, Sheng ; Zhu, Wufu ; Liu, Meng ; Wang, Linxiao ; Fu, Dongxue ; Xu, Shan

Cancer is a leading cause of death in humans. Molecular targeted therapy for cancer has become a research hotspot as it is associated with low toxicity and high efficiency. In this study, a total of 36 derivatives of 4-(4-aminophenoxy)pyridinamide were designed and synthesized, based on the analysis of the binding patterns of cabozantinib and BMS-777607 to MET protein. Most target compounds exhibited moderate to excellent antiproliferative activity against three different cell lines (A549, HeLa and MCF-7). A total of 7 compounds had stronger inhibitory activities than cabozantinib, and the IC₅₀ value of the most promising compound 46 was 0.26 μM against the A549 cells, which was 2.4 times more active than that of cabozantinib. The structure-activity relationship of the target compounds was analyzed and summarized, and the action mechanism was discussed. The acridine orange (AO) staining assay and cell cycle apoptosis revealed that compound 46 dose-dependently induced apoptosis of A549 cells, and blocked the cells mainly in G0/G1 phase. The IC₅₀ value of compound 46 on c-Met kinase was 46.5 nM. Further docking studies and molecular dynamics simulations signaled that compound 46 formed four key hydrogen bonds to c-Met kinase, and these key amino acids played a major role in binding free energy. In addition, compound 46 also showed good pharmacokinetic characteristics in rats. In conclusion, compound 46 is a promising antitumor agent.

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
Metastatic Solid Tumor	Phase 2	-	Aslan Pharmaceuticals Ltd.	01 Oct 2012
Advanced Malignant Solid Neoplasm	Phase 2	AU	Bristol Myers Squibb Co.	01 Mar 2008
Breast Cancer	Phase 2	-	Bristol Myers Squibb Co.	-
Breast Cancer	Phase 2	-	Aslan Pharmaceuticals Ltd.	-
Stomach Cancer	Phase 2	-	Aslan Pharmaceuticals Ltd.	-
Head and Neck Neoplasms	Phase 1	AU	Bristol Myers Squibb Co.	-
Osteoporosis	Phase 1	US	-	-
Prostatic Cancer	Phase 1	AU	Bristol Myers Squibb Co.	-
Renal Cell Carcinoma	Phase 1	AU	Bristol Myers Squibb Co.	-
Stomach Cancer	Phase 1	AU	Bristol Myers Squibb Co.	-

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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	(jstdwlyqll) = zoxvwlbdab idjymmtlof (jvcqfspwzm ) View more	Positive	01 Oct 2018