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GDC-0449 (2-chloro-N-[4-chloro-3-pyridin-2-yl-phenyl]-4-methane-sulfonyl benzamide), discovered by high throughput screening of a small molecule compound library followed by subsequent optimization through medical chemistry, is a potent and selective inhibitor of hedgehog (Hh) signaling, a pathway regulating cell growth and differentiation associated in pathogenesis of several cancers. It binds to signaling by smoothened (SMO) and suppresses activation of downstream Hh target genes resulting in the inhibition of Hh signaling pathway. GDC-0449 exhibits anti-tumor activity in a mouse model of medulloblastoma as well as in primary human tumor cell xenograft models of colorectal cancer and pancreatic carcinoma and is currently being evaluated in research projects investigating refractory, locally advanced or metastatic solid tumors.

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