On May 11, 2021 Anticancer Bioscience (ACB), pioneers in synthetic lethal approaches to precision oncology, reported that progress in its MYC-synthetic lethal (MYC-SL) program (Press release, Anticancer Bioscience, MAY 11, 2021, View Source [SID1234579676]). The Company has identified three classes of novel small molecule compounds that demonstrate robust anti-cancer activity in preclinical studies, acting through interfering with mitosis and blocking cytokinesis. ACB is progressing through optimization and final candidate selection with the goal of progressing at least one of these MYC-SL compounds into clinical trials by 2022.
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The MYC family oncogene, encoding a transcription factor Myc, is deregulated in over 50% of human cancers, and this deregulation is frequently associated with poor prognosis and unfavorable patient survival. Myc has a central role in almost every aspect of the oncogenic process, orchestrating proliferation, apoptosis, differentiation, and metabolism. Direct targeting of Myc has been a challenge for decades owing to its "undruggable" protein structure, with a lack of a drug binding pocket. The synthetic lethality associated with Myc overexpression is being explored for its potential in the development of novel anti-cancer therapies.
Commenting on the progress and pre-clinical data, Dun Yang PhD, Founder, President, and CEO of ACB said:
"We are excited by our early in vitro and in vivo pre-clinical studies and in our molecular biology work to identify the target that our novel compounds hit. In animal models, data consistent with the in vitro studies has confirmed that the MYC-SL compounds act through interfering mitosis and blocking cytokinesis. We have filed patents on our compounds and are progressing rapidly through optimization to candidate selection and IND enabling studies."
The novel target for ACB’s MYC-SL compounds has been identified and will be subject to peer review publication in due course.
ACB has developed an innovative and proprietary general utility new scaffold-drug fragment (GUNS-DF) library approach to small molecule drug discovery. It is constructing 10 types of pilot GUNS-DF libraries, each of which contains a distinct core scaffold. Twenty compounds with excellent drug-like properties have been identified from three types of GUNS-DF libraries with a potency of less than 20 nM in a cell-based assay for MYC-SL agents. This potency was achieved after synthesizing and screening approximately 350 analogs during lead optimization.
At low nM concentrations, these compounds elicited potent cytotoxicity in a panel of 50 cell lines representing a variety of human malignancies. With adequate bioavailability, many of these compounds also suppressed the growth of various cancer cell lines that grew as xenografts in immunocompromised mice.
Having raised CNY131m (~USD21m) in seed finance to fund its discovery research, ACB is currently pursuing a Series A financing to progress at least one of its MYC-SL compounds into clinical trials.
ACB will be showcasing its innovative drug discovery platforms and pipeline at ChinaBio and BioEquity in May, and at BIO in June.