Discovery of a 6-(pyridin-3-yl)benzo[d]thiazole template for optimization of hedgehog and PI3K/AKT/mTOR dual inhibitors.

Abstract:

:Vismodegib is the first FDA approved cancer therapy based on inhibition of aberrant hedgehog signaling. Like most cancer therapies, vismodegib suffered from resistance, even during clinical development. Numerous reports demonstrated that simultaneous blockage of hedgehog and PI3K/AKT/mTOR pathways resulted in significantly superior outcomes compared with single agent alone in a number of animal disease models. The dual hedgehog and PI3K/AKT/mTOR inhibition represented a promising approach not only to overcoming the resistance but also to delaying its onset. Here we report a series of compounds based on a 6-(pyridin-3-yl)benzo[d]thiazole template which have demonstrated significant inhibition of both hedgehog and PI3K/AKT/mTOR signaling pathways. This new scaffold can serve as a lead for further optimization.

journal_name

Bioorg Med Chem Lett

authors

Yang Z,Ma H,Sun Z,Luo L,Tian S,Zheng J,Zhang X

doi

10.1016/j.bmcl.2015.06.049

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

3665-70

issue

17

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(15)00642-3

journal_volume

25

pub_type

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