Acute toxicity analysis of Disarib, an inhibitor of BCL2

Sharma, Shivangi and Varsha, Kontham Kulangara and Kumari, Susmita and Gopalakrishnan, Vidya and Jose, Anjana Elizabeth and Choudhary, Bibha and Mantelingu, Kempegowda and Raghavan, Sathees C. (2020) Acute toxicity analysis of Disarib, an inhibitor of BCL2. Scientific Reports, 10 (1). ISSN 2045-2322

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Abstract

Small molecule inhibitors targeting BCL2 are explored as anticancer therapeutics. Previously, we have reported identification and characterization of a novel BCL2 inhibitor, Disarib. Disarib induced cancer cell death in a BCL2 dependent manner in different cancer cell lines and mouse tumor models when it was administered intraperitoneally. In the present study, using two syngeneic mouse models, breast adenocarcinoma (EAC) and Dalton's lymphoma (DLA), we show that oral administration of Disarib resulted in significant tumor regression in a concentration dependent manner. Importantly, tumor developed in both female and male mice were equally sensitive to Disarib. Further, we have investigated the toxicity of Disarib in normal cells. Single dose toxicity analysis of Disarib in male and female mice after oral administration revealed no significant variations compared to control group for parameters such as body weight, food and water consumption and behavioural changes which were analysed for the entire period of study. Haematological and histopathological analyses also did not show any significant difference from the control groups. Thus, our results reveal safe use of Disarib as a small molecule inhibitor and provide the foundation for investigation of other preclinical studies.

Item Type:	Article
Subjects:	C Chemical Science > Chemistry
Divisions:	Department of > Chemistry
Depositing User:	Mr Umendra uom
Date Deposited:	09 Mar 2021 06:30
Last Modified:	09 Mar 2021 06:30
URI:	http://eprints.uni-mysore.ac.in/id/eprint/15514

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