1335282-35-3

Upstream product

• 82-86-0 acenaphthene quinone 
• 26254-35-3 5-bromoacenaphthylene-1,2-dione 
• 90-05-1 2-methoxy-phenol 

Downstream Products

• 1335282-45-5 3-(2-methoxyphenoxy)-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile 
• 1335282-40-0 2-[2-oxo-2H-6-(2-methoxyphenoxy)acenaphthylen-1-ylidene]malononitrile 

Relevant academic research and scientific papers

Probing the difference between BH3 groove of Mcl-1 and Bcl-2 protein: Implications for dual inhibitors design

Based on our previous discovery of a dual inhibitor of Mcl-1 and Bcl-2, 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (1, S1), and guided by structure insight of 1 complex with Mcl-1 and Bcl-2, we exploited the spatial orientation of BH3 groove of the two proteins by a series of analogues of 1. These analogues contain substitutes with various steric hindrance designed to explore the width and length of the p2 pocket. The structure-activity relationships (SARs) studies together with docking studies and cell-based assays proved that the p2 pocket of Mcl-1 is relatively wider and shorter than that of Bcl-2. A novel dual inhibitor 6 was obtained based on these new findings that it exhibited nanomalar affinities toward Mcl-1 and Bcl-2, as well as nanomalar cytotoxicity activity against multiple cancer cell lines.