DCC-2618 is an oral inhibitor of KIT, PDGFR alpha, PDGFR beta, KDR, and cFMS that is currently in preclinical development.
Manufacturer: Deciphera Pharmaceuticals www.deciphera.com
As detailed in the poster presented by Scott Wise of Deciphera at the fall 2010 GIST Summit meeting (see link below), in cell studies DCC-2618 is able to inhibit not only normal KIT and PDGFRA, but also primary mutations of these genes and the secondary mutations that frequently cause patient resistance to imatinib and suntinib. Successful tumor control has also been shown in a mouse tumor implantation (xenograft).
DCC-2618 is a "switch pocket inhibitor" that has a different mechanism of action than current GIST drugs which are ATP-pocket inhibitors (they compete with ATP to bind a site on the KIT or PDGFRA receptor). The "switch pocket" is a different location on the KIT receptor that acts like a light switch to activate the receptor's signaling. DCC-2618 forces the switch to assume the "off" position.
A trial of DCC-2618 in GIST patients is planned for late 2011.
An earlier presentation about Deciphera pipeline drugs was given at the June 2010 ASCO meeting. At th time of this presentation, the decision had not yet been made which drug to pursue for GIST development, so both DCC-2618 and another molecule are both discussed. Click below for the abstract.
In vitro activity of novel KIT/PDGFRA switch pocket kinase inhibitors against mutations associated with drug-resistant GI stromal tumors.
Presenter: Michael C. Heinrich, MD
J Clin Oncol 28:15s, 2010 (suppl; abstr 10007)