Drug Detail

Information about Discontinued

Generic Name	Amuvatinib
IND	MP470
Brand Name (US)	Discontinued
Manufacturer	SuperGen
Drug Type	Tyrosine Kinase Inhibitor
Delivery	Oral
Approval Status	Discontinued
Indications
Overall Strategy	KIT Protein Based + Oncogenic Signal Path Based
Strategy	Block KIT
Drug Category	KIT/PDGFRA inhibitor

On 9/21/2012, Astex announced that development of amuvatinib would be discontinued.
MP-470 was developed to specifically bind to mutant forms of the c-Kit receptor which are insensitive to current therapies. While a potent inhibitor of wild-type c-Kit, MP-470 displays even greater effectiveness against clinically relevant mutants, including V560G, D816V, N822K and K642E, due to its unique binding mode.
MP470 also inhibits the PDGFRA D842V mutation in-vitro. In addition, it inhibits the AXL receptor. Over time, a subset of GISTs (perhaps 10%) lose expression of KIT and at least some of these appear to switch to a dependence on AXL signaling. See the second link below.
MP-470 is in phase 2 trials. It is also in several phase I trials in combination with chemotherapy.
MP-470 also inhibits Rad51, an important part of the cellular response to DNA damage. Because of this, it is thought that giving chemotherapy that damages DNA at the same time as MP-470, which prevents the tumor cell from repairing the DNA damage, will make the chemotherapy more effective.