Compounds that selectively and effectively inhibit hakai-mediated ubiquitination, as Anti-cancer drugs

Abstract

The present invention provides a class of compounds, which includes enantiomers and pharmaceutically acceptable salts thereof, that selectively and effectively inhibit Hakai-mediated ubiquitination, preferably without affecting Hakai protein levels, thereby representing excellent anti-cancer drugs useful in the treatment of a variety of cancers, such as carcinomas, in particular, tumors arising from the epithelial layers of the gastrointestinal track including month (oral cancer), esophagus, stomach, and small and large intestines (such as rectal or colon cancer). It also includes skin cancer, mammary gland (breast cancer), pancreas cancer, lung cancer, head and neck cancer, liver cancer, ovary cancer, cervix cancer, uterus cancer, gallbladder cancer, penile cancer, and urinary bladder cancer (such as renal, prostate or bladder cancer).

Description

technical field [0001] The present invention relates to a new class of compounds and compositions comprising the compounds. The compounds and compositions (eg, pharmaceutical compositions) of the invention are useful as agents for the treatment of cancer. Background technique [0002] Carcinoma, the most common type of cancer, arises from epithelial cells. The transition from adenoma to carcinoma is associated with loss of E-cadherin and, as a result, disruption of cell-cell contacts. E-cadherin is a tumor suppressor that is downregulated during Epithelial-to-mesenchymal transition (EMT); indeed, its loss is a predictor of poor prognosis. Hakai is an E3 ubiquitin ligase protein that mediates E-cadherin ubiquitination, endocytosis, and eventual degradation, resulting in altered cell-cell contacts. Although E-cadherin is the most established substrate for Hakai activity, other regulated molecular targets of Hakai may be involved in cancer cell plasticity during tumor progre...

AI Technical Summary

Problems solved by technology

However, until now, no compounds capable of effectively inhibiting Hakai-mediated ubiquitination have been disclosed that are particularly suitable as therapeutic tools for the treatment of cancer.

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