Description
BMS 754807 is a reversible, orally bioavailable dual inhibitor of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (InsR) tyrosine kinases (IC
50s = 1.8 and 1.7 nM, respectively).
1,2 It has minimal effect against an array of other tyrosine and serine/threonine kinases.
1 BMS 754807 inhibits cell proliferation or induces apoptosis in a variety of cancer cells
in vitro.
2 It inhibits the growth of tumor xenografts in mice and this effect is often enhanced by combination therapy with other chemotherapeutics.
2,3,4 Predictive biomarkers, including elevated IGF-1R expression, for effectiveness of BMS 754807 have been delineated.
5
Uses
An IGF-1R inhibitor with an IC50 of 13 nM.
Uses
BMS 754807 is a reversible, orally bioavailable dual inhibitor of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (InsR) tyrosine kinases (IC50s = 1.8 and 1.7 nM, respectively). It has minimal effect against an array of other tyrosine and serine/threonine kinases. BMS 754807 inhibits cell proliferation or induces apoptosis in a variety of cancer cells in vitro. It inhibits the growth of tumor xenografts in mice and this effect is often enhanced by combination therapy with other chemotherapeutics. Predictive biomarkers, including elevated IGF-1R expression, for effectiveness of BMS 754807 have been delineated.[Cayman Chemical]
Definition
ChEBI:BMS-754807 is a pyrrolotriazine that is pyrrolo[2,1-f][1,2,4]triazine which is substituted at position 2 by the pyrrolidine nitrogen of (2S)-N-(6-fluoropyridin-3-yl)-2-methylprolinamide, and at position 4 by a (5-cyclopropyl-1H-pyrazol-3-yl)amino group. It is a potent, reversible inhibitor of the insulin-like growth factor 1 receptor/insulin receptor family kinases. It has a role as an EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor and an antineoplastic agent. It is a pyrrolotriazine, a member of pyrazoles, a member of pyridines and a member of pyrrolidines.
General Description
BMS-754807 is a pyrrolotriazine, which is a potent dual inhibitor of insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (InsR) tyrosine kinase. It has been reported that BMS-754807 also acts as a reversible ATP-competitive antagonist of IGF-1R by restricting the catalytic domain of the IGF-1R.
Biochem/physiol Actions
BMS-754807 is an orally available and potent dual insulin-like growth factor factor-1 receptor (IGF-1R)/ insulin receptor (InsR) tyrosine kinase inhibitor that synergistically enhances antiproliferative effects of 4-hydroxytamoxifen, letrozole, and fulvestrant in MCF-7/AC-1 cells.
References
[1] q.s. chu，s.w. kim，p.m. ellis，l. mileshkin，r.h. de boer，j.s. park，t. pellas，f. huang，f. graf finckenstein，a. dhar. bms-754807, an oral dual igf-1r/insulin receptor (ir) inhibitor: initial results from a phase 1 dose- and schedule-?nding study in combination with carboplatin/paclitaxel in subjects with solid tumors. european journal of cancer supplements. november 2010, 8(7): 131.
[2] vattoly j. majo, victoria arango, norman r. simpson, jaya prabhakaran, suham a. kassir, mark d. underwood, mihran bakalian, peter canoll, j. john mann, j.s. dileep kumar. synthesis and in vitro evaluation of [18f]bms-754807: a potential pet ligand for igf-1r. bioorganic & medicinal chemistry letters. july 2013, 23(14): 4191-4194.
[3] joan m. carboni, mark wittman, zheng yang, et al.. bms-754807, a small molecule inhibitor of insulin-like growth factor-1r/ir. mol cancer ther. 2009;8:3341-3349.
