Research

Pharmaceutical Sciences

Title :

Development of new Smac Mimetic against chemotherapy resistant colon cancer

Area of research :

Life Sciences & Biotechnology, Medical Sciences, Pharmaceutical Sciences

Focus area :

New molecule development against chemo-resistant colon cancer

Principal Investigator :

Dr Dipak Datta, Scientist, CSIR-Central Drug Research Institute (CSIR-CDRI), Uttar Pradesh

Timeline Start Year :

2020

Timeline End Year :

2022

Contact info :

Details

Executive Summary :

Objective: Gm level Synthesis, Initiation of Pharmacokinetic studies of S016-1348; Completion of PK studies and in-vivo efficacy determination as monotherapy; Efficacy comparison with phase-II molecule comparator, evaluation of therapeutic potential as combination therapy and mode of action / target validation studies; Initial toxicity studies, patent filing and preparation of IND enabling studies

Summary: Currently, multiple Smac mimetic molecules are in Phase-I and Phase-II clinical trials as monotherapy or combination therapy in different cancers. CDRI has more potent novel Smac peptide-mimetic which is active against chemotherapy resistant colon cancer. Completed study highlights: a. Patentable (URDIP) novel SMAC mimetic (S016-1348) synthesized b. Target binding confirmed c. In-vitro activity and safety efficacy established, more potent than currently available Phase-II molecules (LCL-161, Birinapant, AT406) d. Solubility, stability determined e. In-vivo active in Cisplatin resistant colon tumor xenograft models through IP and s.c route: Proof of Concept (POC) generated f. Target (SMAC) dependent hallmark apoptotic features validated Project Unique Project Identification Number (UPIN): Institutional Approval Reference: Date of Opening: Date of Completion: Budget: CSIR Fast-Track Translation (FTT) Project Project Mentor(s) 1. Name: Prof. Tapas Kundu, Director, CSIR-CDRI Email: director@cdri.res.in Telephone (O) 0522 2771940 2. Name: Email: Telephone (O) Telephone (M) g. Initial PK detected pure molecule in good quantity in mice plasma after oral, i.p, s.c routes; s.cis the best. Tumor retention 3-4 times higher than in-vitro cellular IC50 concentrations. h. In-vivo efficacy through s.c route has been re-validated in another colon cancer xenograft models in nude mice.

Organizations involved