AZ 12080282 dihydrochloride

AZ 12080282 dihydrochloride is a selective inhibitor of Hh with IC50 value <0.012 μM [1]. It is also reported that AZ 12080282 also has a selective inhibition to p38α with low nanomolar potency [1].

Hedgehog (Hh) signaling plays an important role in a wide variety of developmental processes, including larval body segment development and adult appendages formation. Abnormal activation of Hh pathway may lead to developmental disease by transforming adult stem cells into cancer stem cells and also leads to cancers via increasing in Angiogenic Factors, Cyclins, anti-apoptotic genes and decreasing in apoptotic genes [2].

AZ 12080282 is a potent Hh inhibitor and is different from the other reported Hh inhibitors. When tested with Gli transcription factor reporter cell, AZ 12080282 treatment resulted in the Hh signaling pathway inhibition by using shh stimulated cell differentiation assay [1].

References:
[1].  Yang, B., et al., Discovery of novel hedgehog antagonists from cell-based screening: Isosteric modification of p38 bisamides as potent inhibitors of SMO. Bioorg Med Chem Lett, 2012. 22(14): p. 4907-11.
[2].   D'Amato, C., et al., Inhibition of Hedgehog signalling by NVP-LDE225 (Erismodegib) interferes with growth and invasion of human renal cell carcinoma cells. Br J Cancer, 2014. 111(6): p. 1168-79.