AI Based Discovery of a New AKR1C3 Inhibitor for Anticancer Applications.

AKR1C3 is an upregulated enzyme in prostate and other cancers; in addition to regulating hormone synthesis, this enzyme is thought to play a role in the aggressiveness of tumors and in the defense against drugs. We here used an unbiased method to discover new potent AKR1C3 inhibitors: through an AI-based virtual drug screen, compound was identified as a potent and selective enzymatic inhibitor able to translate this activity into a pronounced antiproliferative effect in the 22RV1 prostate cancer cell model. As other known AKR1C3 inhibitors, compound determined a significantly increased activity of abiraterone, a drug approved for advanced prostate cancer.

Structure-guided optimization of 3-hydroxybenzoisoxazole derivatives as inhibitors of Aldo-keto reductase 1C3 (AKR1C3) to target prostate cancer.

AKR1C3 is an enzyme that is overexpressed in several types of radiotherapy- and chemotherapy-resistant cancers. Despite AKR1C3 is a validated target for drug development, no inhibitor has been approved for clinical use. In this manuscript, we describe our study of a new series of potent AKR1C3-targeting 3-hydroxybenzoisoxazole based inhibitors that display high selectivity over the AKR1C2 isoform and low micromolar activity in inhibiting 22Rv1 prostate cancer cell proliferation.

Phenothiazines as anti-cancer agents: SAR overview and synthetic strategies.

Cancer is a leading cause of death worldwide and there are still limited options for cure. Chemotherapy is the most significant treatment for cancer which increased survival rates, despite this, it is associated with numerous side effects, as well as cancer relapsing due to drug resistance insurgence; consequently, it is still a challenging task to develop new potent and less toxic anti-cancer agents for patients' care. Phenothiazine moiety, which leads a class of well-known antipsychotic drugs, possesses a wide range of biological activities and has been also introduced in cancer chemotherapy.