Description
The Aurora kinases are a family of serine/threonine kinases that are key regulators of mitosis and cytokinesis. PF-
03814735 is a reversible inhibitor of both Aurora A and B kinases with IC
50 values of 0.8 and 5 nM, respectively, in
in vitro activity assays. PF-
03814735 also inhibits the kinases FLT1, FAK, TrkA, Met, and FGFR1 with IC
50 values of 10, 22, 30, 100, and 100 nM, respectively. PF-
03814735 inhibits cell proliferation of HCT116, HL-
60, A549, and H125 tumor cell lines with IC
50 values ranging from 42-
150 nM and shows
in vivo efficacy in an HCT116 tumor xenograft mouse model. PF-
03814735 has been shown to be particularly sensitive towards inhibiting the growth of small cell lung cancer cell lines and other tumors driven by the Myc family genes.
Chemical Properties
Off-White Solid
Uses
The Aurora kinases are a family of serine/threonine kinases that are key regulators of mitosis and cytokinesis. PF-03814735 is a reversible inhibitor of both Aurora A and B kinases with IC50 values of 0.8 and 5 nM, respectively, in in vitro activity assays. PF-03814735 also inhibits the kinases FLT1, FAK, TrkA, Met, and FGFR1 with IC50 values of 10, 22, 30, 100, and 100 nM, respectively. PF-03814735 inhibits cell proliferation of HCT-116, HL-60, A549, and H125 tumor cell lines with IC50 values ranging from 42-150 nM and shows in vivo efficacy in an HCT-116 tumor xenograft mouse model. PF-03814735 has been shown to be particularly sensitive towards inhibiting the growth of small cell lung cancer cell lines and other tumors driven by the Myc family genes.[Cayman Chemical]
Uses
PF 03814735 is an orally bioavailable small molecule aurora kinase inhibitor that plays a key role in the regulation of mitosis. PF 03814735 is a anticancer agent used for cancer therapy.
in vivo
Once-daily oral administration of PF-03814735 to mice bearing human xenograft tumors produces a reduction in phosphohistone H3 in tumors at doses that are tolerable and that result in significant inhibition of tumor growth. The combination of PF-03814735 and docetaxel in xenograft mouse tumor models shows additive tumor growth inhibition[1]. PF-03814735 is much more effective in NCI-H82 xenografts when administered on a weekly dosing schedule at 80 mg/kg compared with a daily schedule at 15 mg/kg. PF-03814735 delayed growth by 23.5 days on the weekly schedule, which corresponds to 0.9 logs of net cell kill during the course of treatment[2].
IC 50
Aurora 1: 0.8 nM (IC
50); Aurora 2: 5 nM (IC
50); Flt-1: 10 nM (IC
50); FAK: 22 nM (IC
50); TrkA: 30 nM (IC
50); Met: 100 nM (IC
50); FGFR1: 100 nM (IC
50)
References
[1] jani jp, arcari j, bernardo v, bhattacharya sk, briere d, cohen bd, coleman k, christensen jg, emerson eo, jakowski a, hook k, los g, moyer jd, pruimboom-brees i, pustilnik l, rossi am, steyn sj, su c, tsaparikos k, wishka d, yoon k, jakubczak jl. pf-03814735, an orally bioavailable small molecule aurora kinase inhibitor for cancer therapy. mol cancer ther. 2010 apr;9(4):883-94.
