SummaryThe piecewise linear approximation method is used to estimate the non‐linear functions, which is implemented by the shift‐and‐add architecture consisting of three blocks: “adder tree,” “multiplexer,” and “segment index encoder.” Compared with state of the art, the design flow in this letter enables the “adder tree” and “multiplexer” blocks can be shared by multiple nonlinear functions. In other words, the shift‐and‐add architecture can approximate multiple nonlinear functions with a slight overhead. The fused Log and Antilog converter demonstrates the feasibility of the proposed method. The Antilog function is implemented by the Log converter at the cost of 14% cell area and 6% delay.
The hedgehog (Hh) pathway is critically important for embryonic development, and interference with the Hh pathway could result in severe birth defect. The Hh pathway is known to be highly activated in certain cancers such as basal cell carcinoma (BCC) and medulloblastoma. The approval of hedgehog pathway inhibitor Erivedge (vismodegib, GDC-0445) for the treatment of adults BCC by FDA in early 2012 validated Hh pathway as an anticancer target.In this presentation, we report the discovery of novel hedgehog pathway inhibitors and the identification of lead compounds that are 10-100 fold more potent in multiple in vitro assays than GDC-0449. Several of these potent compounds have been found to have good oral bioavailability and brain penetration. The in vivo efficacy studies of selected compounds are in progress.
Citation Format: Sui Xiong Cai, Kai Xie, Sicun Li, Lizhen Wu, Lijun Liu, Feng Yin, Chengyun Gu, Xiaozhu Wang, Sishun Kang, Shengzhi Chen, Zheng Meng, Yan Zhang, Guoxiang Wang, Hongqiang Fei, Dongmei Wang, Ye Edward Tian. Discovery of potent hedgehog pathway inhibitors as potential anticancer agents. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2243A. doi:10.1158/1538-7445.AM2013-2243A
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