Using AI, Insilico Medicine Finds A Potential New Target For Gynaecological And Breast Malignancies

Insilico Medicine Finds A Potential New Target For Gynaecological And Breast Malignancies | The Lifesciences Magazine

As a promising new therapeutic target for breast and gynaecological cancer, MYT1 has been identified by Insilico Medicine (“Insilico”), a clinical stage generative artificial intelligence (AI)-driven drug discovery company. Insilico Medicine has also discovered a series of novel, potent, and highly selective inhibitors that specifically target MYT1. These results, which were published in the Journal of Medicinal Chemistry in December 2023, were backed by Insilico’s AI-driven generative biology and chemistry engine.

Insilico Medicine Finds

Breast and gynaecological malignancies are major global health and reproductive hazards to women’s quality of life. The research team uses Insilico Medicine’s unique AI-driven target identification platform, PandaOmics, to analyse data of five types of gynaecological cancers, including ovarian, endometrial, cervical, and breast cancer, especially triple-negative breast cancer, in order to find possible targets for new therapeutics. Interestingly, MYT1 was consistently the most relevant gene across all disorders.

A member of the Wee1-kinase family, MYT1 is substantially expressed in the majority of cancer types but is infrequently expressed in most normal tissues. According to reports, CCNE1 amplification, also referred to as synthetic lethality, and MYT1 inhibition both have important roles in the regulation of the cell cycle. This suggests that MYT1 inhibition is a promising therapeutic approach for the treatment of cancers with genome instability, such as CCNE1 amplification.

Nevertheless, the great similarity between MYT1 and Wee1 poses a difficulty in creating MYT1 inhibitors that are selective. Using the assistance of Chemsitry42, Insilico’s AI-driven small molecule creation platform, the company tackled the shortage of selective MYT1 inhibitors in this investigation. By employing structure-based drug design (SBDD) techniques and implementing stringent filters for selectivity and similarity, Insilico Medicine created a variety of molecules that specifically target MYT1. One series of these new chemicals turned out to be successful.

Subtle changes to the chemical structure have a major impact on the complex’s activity, according to Insilico’s x-ray crystal structure research. With the use of this information, Insilico Medicine was able to carry out additional molecular optimisation and ultimately identify molecule 21, the lead molecule. Compound 21 exhibits strong MYT1 activity and superior selectivity compared to Wee1 and the other kinase panel, which may result in a safer profile by lowering the possibility of off-target effects. It also demonstrates strong in vivo anticancer activity and a favourable profile in ADME and PK/PD in preclinical trials.

The innovative approach of this program has not only present a method for effective target identification but has also led to the development of a promising selective MYT1 inhibitor. Compound 21 expands Insilico’s synthetic lethal pipeline and paves the way toward a safer, more effective therapeutic future for patients battling” gynecological and breast cancers.”

Yazhou Wang, Ph.D., medicinal chemistry leader of the MYT1 program from Insilico Medicine, and the first author of this paper

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