Dubermatinib | AXL inhibitor

Dubermatinib (1341200-45-0) is a potent (IC₅₀ = 27 nM) inhibitor of the TAM family kinase AXL.¹ It displayed potent activity against the pancreatic tumor cell line PSN-1 (IC₅₀ = 6 nM). Dubermatinib also strongly inhibited the kinases Aurora A/B, JAK2, ABL1, and CHEK1.  It induced apoptosis in chronic lymphocytic leukemia (CLL) cells and acted synergistically with BTK inhibitors against CLL cells.² It inhibited neuroblastoma cell growth and enhanced sensitivity to conventional chemotherapy.³ Dubermatinib was also active in a drug-resistant acute myeloid leukemia model⁴ and reduced metastasis and therapy resistance in pancreatic cancer models⁵.

References/Citations:

1. Mollard et al. (2011), Design, Synthesis, and Biological Evaluation of a Series of Novel AXL Kinase Inhibitors; ACS Med. Chem. Lett. 2 907
2. Sinha et al. (2015); Targeted Axl Inhibition Primes Chronic Lymphocytic Leukemia B Cells to Apoptosis and Shows Synergistic/Additive Effects in Combination with BTK Inhibitors; Clin. Cancer Res. 21 115
3. Aveic et al. (2018); TP-0903 inhibits neuroblastoma cell growth and enhances the sensitivity to conventional chemotherapy; Eur. J. Pharmacol. 818 435
4. Jeon et al. (2020); TP-0903 is active in models of drug-resistant acute myeloid leukemia; JCI Insight 5 e140169
5. Zhang et al. (2022); Axl Inhibitor TP-0903 Reduces Metastasis and Therapy Resistance in Pancreatic Cancer; Mol. Cancer Ther. 21 38