XMD16-5

Description: XMD16-5 is a novel and potent tyrosine kinase nonreceptor 2(TNK2) inhibitor with IC50s of 16 nmol/L and 77 nmol/L for the D163E and R806Q mutations. TNK2 mutations were found in renal cancer cells and also in lung, ovarian and gastric cancers. TNK2 genomic amplification has been associated with late stage or metastatic lung and prostate cancers. Overexpression of TNK2 promoted metastasis in a mouse model of breast cancer. TNK2 signaling is disrupted in prostate, breast and gastrointestinal tumors. XMD8-87 and XMD16-5 potently inhibit phosphorylation of TNK2 truncation mutations found in solid tumor types. XMD16-5 was identified from kinase inhibitor screens to predict functional gene targets in primary specimens from patients with acute myeloid leukemia and chronic myelomonocytic leukemia. Deep sequencing of the same patient specimens identified genetic alterations that were then integrated with the functionally important targets using the HitWalker algorithm to prioritize the mutant genes that most likely explain the observed drug sensitivity patterns.

References: Cancer Res. 2016 Jan 1; 76(1):127-38.