Mahatinib

**Semantic type:** Pharmacologic Substance

**Definition:** An orally bioavailable small molecule inhibitor of activated CDC42 kinase 1 (ACK1; non-receptor tyrosine kinase 2; TNK2), with potential antineoplastic activity. Upon oral administration, mahatinib targets, binds to and inhibits the activity of ACK1. This disrupts the phosphorylation of histones and prevents the transcription and expression of the androgen receptor (AR) including splice variant AR-v7. In addition, this disrupts the phosphorylation of C-terminal Src kinase (CSK) at tyrosine 18 (pY18) and inhibits ACK1/pY18-CSK signaling, which may lead to T-cell activation and enhanced immune response against tumor cells. Altogether, this may inhibit tumor cell proliferation. ACK1, an oncogenic non-receptor tyrosine kinase, is involved in the epigenetic upregulation of AR and AR-v7 expressions and may play a role in the downregulation of the immune system.

**Synonyms:** - (R)-9b - (R)-9b MS - (R)-9b-MS - (R)-9bMS