Mahatinib (R)-9bA Novel Dual-Action Anti-Cancer Agent
Targeting ACK1 Tyrosine Kinase to defeat:
The Science
Inside Mahatinib (R)-9b
Chemical structure of (R)-9b (Mahatinib)
A NOVEL SMALL MOLECULE, AR-ANTAGONIST
(R)-9b is a small molecule inhibitor that suppresses activity of AR-interacting tyrosine kinase, ACK1 (also known as TNK2). ACK1/AR complex regulates AR and AR-V7 expression. By virtue of ACK1 inhibition, (R)-9b suppresses not only AR (and AR-V7) expression, but also overcomes tumor growth of Castration Resistant Prostate Cancer (CRPC). Significantly, (R)-9b sensitizes Enzalutamide and Abiraterone-resistant prostate cancer, opening a new therapeutic modality for these patients, a critical unmet need.
A NEW CLASS OF IMMUNE MODULATOR
(R)-9b is an UNIQUE molecule with dual-inhibitory activity: it not only acts on cancer cells by acting as an AR-antagonist, but also elicits CD8+ T cells, the host immune response against cancer cells. This dual activity makes this compound a highly effective inhibitor against prostate cancer, drug-resistant breast and lung cancers. This is highly relevant as immune checkpoint blockade (ICB) antibodies have modest response in prostate and breast cancers. Thus, (R)-9b emerged as a new class of dual-action immune modulator that can sensitize these difficult to treat cancers.
Read the full mechanism of action →
ACK1-mediated AR transcription pathway in CRPC
Leadership
.jpg)