an optically pure apogossypolone derivative as potent pan-active inhibitor of anti-apoptotic bcl-2 family proteins

Clicks: 357
ID: 133421
2011
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Star

Ranked #46 of 207 articles by views in international journal of heat and technology

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 207 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Our focus in the past several years has been on the identification of novel and effective pan-Bcl-2 antagonists. We have recently reported a series of Apogossypolone (ApoG2) derivatives, resulting in the chiral compound (+/-) BI97D6. We report here the synthesis and evaluation on its optically pure (-) and (+) atropisomers. Compound (-) BI97D6 potently inhibits the binding of BH3 peptides to Bcl-XL, Bcl-2, Mcl-1 and Bfl-1 with IC50 values of 76 ± 5, 31 ± 2, 25 ± 8 and 122 ± 28 nM, respectively. In a cellular assay, compound (-) BI97D6 effectively inhibits cell growth in the PC-3 human prostate cancer and H23 human lung cancer cell lines with EC50 values of 0.22 ± 0.08 and 0.14 ± 0.02 µM, respectively. Similarly, compound (-) BI97D6 effectively induces apoptosis in the BP3 human lymphoma cell line in a dose-dependent manner. The compound also shows little cytotoxicity against bax-/-/bak-/- cells, suggesting that it kills cancers cells predominantly via a Bcl-2 pathway. Moreover, compound (-) BI97D6 displays in vivo efficacy in both a Bcl-2 transgenic mouse model and in a prostate cancer xenograft model in mice. Therefore, compound (-) BI97D6 represents a promising drug lead for the development of novel apoptosis-based therapies for cancer.
Reference Key
ewei2011frontiersan Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Jun eWei, John L Stebbins, Shinichi eKitada, Rupesh eDash, Dayong eZhai, William J Placzek, Bainan eWu, Michele F Rega, Ziming eZhang, Elisa eBarile, Li eYang, Russell eDahl, Paul B. Fisher, John C Reed, Maurizio ePellecchia
Are you one of these authors? Claim your profile
Journal international journal of heat and technology
Year 2011
DOI
10.3389/fonc.2011.00028
URL
http://journal.frontiersin.org/Journal/10.3389/fonc.2011.00028/full
Keywords
5 Cancer apoptosis Oncology including cancer and carcinogens tumors apogossypoloneneoplasms

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.