Src inhibitor

Src inhibitor is a class of inhibitors that targets src kinase family of tyrosine kinases, which is transcribed by proto-oncogenes src genes (abbreviating for sarcome genes) that potentially induced cell of malignant transformation. Because of the crucial position of src gene/kinase in cells, src inhibitors are potential antineoplastic agents for pancreatic cancer, breast cancer, stomach cancer etc.[1]

chemical structure of KX2-391

Examples

• KX2-391 is an oral src inhibitor and the first clinical inhibitor with GI50 of 9–60 nM in cancer cell lines.[2]
• Bosutinib has been developed for the treatment of chronic myelogenous leukemia by Pfizer.
• Saracatinib, the first Src inhibitor to show inhibition of the Src pathway in human tumor tissue, has anti-tumor activity alone or in combination with chemotherapeutic agents.[3]

chemical structure of PP1

• PP1, PP2 (kinase inhibitor) are both inhibitors of Lck and FynT.[4][5]
• Dasatinib[1][6]

References

1. Rivera-Torres J, José ES (2019). "Src Tyrosine Kinase Inhibitors: New Perspectives on Their Immune, Antiviral, and Senotherapeutic Potential". Frontiers in Pharmacology. 10: 1011. doi:10.3389/fphar.2019.01011. PMC 6759511. PMID 31619990.
2. Antonarakis ES, Heath EI, Posadas EM, Yu EY, et al. (Apr 2013). "A phase 2 study of KX2-391, an oral inhibitor of Src kinase and tubulin polymerization, in men with bone-metastatic castration-resistant prostate cancer". Cancer Chemother Pharmacol. 71 (4): 883–892. doi:10.1007/s00280-013-2079-z. PMC 3609871. PMID 23314737.
3. Nam HJ, et al. "Antitumor activity of saracatinib (AZD0530), a c-Src/Abl kinase inhibitor, alone or in combination with chemotherapeutic agents in gastric cancer". Mol. Cancer Ther. 12 (1): 16–26. doi:10.1158/1535-7163.MCT-12-0109. PMID 23144237.
4. "PP1 is a potent and selective Src inhibitor for Lck/Fyn".
5. "biological activity of PP2 in selleck chemicals". Selleck Texas.
6. Chan CM, Jing X, Pike LA, Zhou Q, Schweppe RE (2012). "Targeted inhibition of Src kinase with dasatinib blocks thyroid cancer growth and metastasis". Clinical Cancer Research. 18 (13): 3580–91. doi:10.1158/1078-0432.CCR-11-3359. PMC 3931551. PMID 22586301.