COMMENT Chemical Neighbourhood for QSAR: 18 molecules similar (>0.80) to CP-673451 with in vitro affinities for PDGFRbeta were found in public repositories (e.g., ChEMBL). On-Target links to toxicities: PDGFRbeta has been associated with hemotoxicities (e.g., bleeding, hemorrhage, cytopenia). Jul 13 2016 - 4:25pm; The limited public information on this compound does not provide high confidence in its utility as a probe to evaluate PDGFR biology. The probe has been reported to enzyme potency in 1-10 nM range with cell activity below 10 nM. The good translation from enzyme to cell readout considering the Km for PDGFRb is reported to be 4 uM is unexpected. The selectivity using 100 nM concentration of compound for a very limited number of kinases is acceptable. The chemotype has been reported to hit many kinases, and the kinome-wide selectivity must be profiled if this tool is being used to discover novel biology to ensure that it is not originating from an unknown off-target. Crenolanib, a very similar compound, has potent activity on FLT3 and mutant cKIT, neither of which have been evaluated for this compound. In general, the compound could be used in cell-based assays at concentration below 100 nM, which would be around the IC90 for the target based on reported data. Aug 22 2016 - 12:37pm; The published data for CP-673451 indicates that it is a highly potent and selective inhibitor of PDGFR relative to other anti-antiogenic receptors, including VEGFR, TIE-2 and c-KIT, though the panel of kinases that have been measured is limited (<50). The compound has excellent in vivo activity in terms of anti-tumor growth and inhibition of PDGFR-beta phosphorylation, and it was demonstrated to have ex-vivo pharmacodynamic effects in a sponge angiogenesis model. Because CP-673451 is nonselective with regards to PDGF-alpha (~10-fold in vitro and in cells), this compound cannot discern what contribution to in vivo antitumor efficacy is due to PDGFR-beta versus alpha, nor if other kinases that were not tested contribute to the in vivo profile. A full assessment of the utility of the probe still requires broad kinase profiling (e.g., against the DiscoverX panel of >400 kinases). Appropriate application will require users to tease apart the contributions of PDGFR-beta and alpha. Nonetheless, the suitable properties of CP-673451 and its potent in vivo pharmacodynamic activity with excellent tolerability make it a useful probe for interrogating the impact of PDGF-beta inhibition. Nov 2 2016 - 1:48pm; This probe has been extensively characterize in vivo and has demonstrated on-target pharmacodynamic activity in various xenograft models at doses that were well tolerated. CP-673451 shows good selectivity against a panel receptor tyrosine kinases, as well as broad kinase selectivity against a set of representative kinases. The fact that the probe lacks selectivity against PDGFR-alpha (i.e., is within 10-fold potency in vivo and in cells relative to PDGFR-beta) and has not been profiled against a broader set of kinases makes it difficult to ascribe in vivo efficacy exclusively to PDGFR-beta. Nonetheless, its potent biochemical and cellular activity against PDGFR-beta and the fact that it covers the target well in vivo make it a fairly useful probe to study the importance of PDGFR-beta in an in vivo setting. To fully rule out off target activities in vivo, a more complete set of kinase data would be desirable. Nov 4 2016 - 11:07am

DESCRIPTION CP-673451 is an investigational, selective inhibitor of PDGFRα and PDGFRβ .
A bioRxiv preprint reports on a machine learning approach that was used to identify CP-673451 as a (low potency) anti-tumour agent in glioblastoma multiforme (GBM) stem cell lines . (GtoPdb)

DESCRIPTION CP-673451 is a potent and selective inhibitor of PDGFR with IC50s of 10 and 1 nM for PDGFR¦Á and PDGFR¦Â, respectively.

PRICE 158

DESCRIPTION CP-673451 is a specific inhibitor of PDGFR??/?? (IC50: 10/1 nM) with antiangiogenic and antitumor activity and the selectivity is higher 450-fold than other angiogenic receptors.

MOA Inhibitor (Chemical Probes.org)

DESCRIPTION Selective myeloperoxidase (MPO) inhibitor (Tocris Bioactive Compound Library)

DESCRIPTION CP-673451 is a selective inhibitor of PDGFRα/β with IC50 of 10 nM/1 nM, exhibits >450-fold selectivity over other angiogenic receptors, has antiangiogenic and antitumor activity. (BOC Sciences Bioactive Compounds)

DESCRIPTION CP-673451 is a specific inhibitor of PDGFRα/β (IC50: 10/1 nM) with antiangiogenic and antitumor activity and the selectivity is higher 450-fold than other angiogenic receptors. (TargetMol Bioactive Compound Library)