Sunday, March 22, 2015

Drugs in Clinical Pipeline: Altiratinib

Altiratinib [N-[4-({2-[(cyclopropylcarbonyl)amino]pyridin-4-yl}oxy)-2,5-difluorophenyl]-N’-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide] is a multi-kinase inhibitor targeting MET/TIE-2/VEGFR-2/TRK A,B,C kinases. It is in Phase 1 clinical development for the treatment of invasive solid tumors including glioblastoma.

IPUAC Name: N-[4-({2-[(cyclopropylcarbonyl)amino]pyridin-4-yl}oxy)-2,5-difluorophenyl]-N’-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
Common Name: DCC-2701; DCC 2701;  DCC2701; DP-5164; DP 5164
Originator: Deciphera Pharmaceuticals

The U.S. Food and Drug Administration has granted Altiratinib Orphan Drug Designation for glioblastoma.

Altiratinib is designed as with the purpose of inhibiting MET and TRK kinases as cancer driver mutations alongwith incorporating a balanced inhibition of the tumor micro-environment via MET, TIE-2, and VEGFR-2 kinases within a single therapeutic. With its balanced potency, Altiratinib can inhibit three major tumor vascularization pathways (HGF, VEGF, ANG), thus overcoming the problem of tumor evasive vascularization, allowing for durable MET or TRK inhibition in tumors and overcoming HGF/MET mediated drug resistance.

Altiratinib has pharmaceutical properties amenable to oral administration and also exhibits substantial blood-brain-barrier penetration, making Altiratinib a promising candidate for the treatment of glioblastoma multiforme (GBM).

Altiratinib may also be active against MET-driven cancers, such as melanoma, pancreatic cancer, gastric tumors, renal cell carcinoma (RCC) and BRAF-mutated melanoma as well as TRK-driven cancers such as non-small cell lung cancer (NSCLC), acute myeloid leukemia (AML), colorectal cancer, ovarian cancer and thyroid cancer.

Article citation: Flynn, D.; et. al. Altiratinib (DCC-2701): a balanced inhibitor of MET, TIE2, and VEGFR2 kinases that exhibits broad anti-tumor and anti-angiogenic activities. EJC 2014, 50(6), 115.