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.
