CUR 61414 is a potent inhibitor of hedgehog-induced cellular activity (IC50 = 100-200 nM). It binds directly with the pathway activator Smoothened (Ki = 44 nM). CUR 61414 blocks proliferation and induces apoptosis in mouse basal cell carcinoma and causes regression of basaloid lesions triggered by ultraviolet light in mouse skin.
CUR 61414 is a proline derivative as mediator of hedgehog signaling pathways for pharmaceutical and cosmetic uses. CUR 61414 is a Nucleoside analog. CUR 61414 is an antimetabolite antitumor combination Gemcitabine cancer treatment
previous study found that cur61414 was able to arrest proliferation of basal cells within the bcc-like lesions and induce cells to undergo apoptosis resulting in complete regression of the lesions, without affecting neighboring skin cells [1].
the efficacy of cur61414 against basaloid lesions induced when mice were exposed to uv light. these mice were uv irradiated for 6-9 months, producing many microscopic bcc-like basaloid lesions throughout their skin. results showed that the treatment with cur61414 could cause regression of these lesions, as demonstrated by both x-gal staining and histological analyses. moreover, the regression in the cur61414-treated mice seemed to be the result of massive cell death, becuase a significant increase in apoptotic nuclei was seen in basaloid nests after treatment. in addition, no overt toxicity was observed in the skin surrounding the lesions [1].
100-200 nm for hedgehog-induced cellular activity
1) Williams et al. (2003), Identification of a small molecule inhibitor of the hedgehog signaling pathway: effects on basal cell carcinoma-like lesions; Proc.Natl. Acad. Sci. USA, 100 4616
2) Tang et al. (2011), Targeting superficial or nodular Basal cell carcinoma with topically formulated small molecule inhibitor of smoothened; Clin. Cancer Res., 17 3378
3) Athar et al. (2004), Inhibition of smoothened signaling prevents ultraviolet B-induced basal cell carcinomas through regulation of Fas expression and apoptosis; Sci. Signal., 64 7545
