Literature DB >> 26819663

Discovery of the Selective CYP17A1 Lyase Inhibitor BMS-351 for the Treatment of Prostate Cancer.

Audris Huang1, Lata Jayaraman1, Aberra Fura1, Gregory D Vite1, George L Trainor1, Marco M Gottardis1, Thomas E Spires1, Vanessa M Spires1, Cheryl A Rizzo1, Mary T Obermeier1, Paul A Elzinga1, Gordon Todderud1, Yi Fan1, John A Newitt1, Sophie M Beyer1, Yongxin Zhu1, Bethanne M Warrack1, Angela K Goodenough1, Andrew J Tebben1, Arthur M Doweyko1, David L Gold1, Aaron Balog1.   

Abstract

Efforts to identify a potent, reversible, nonsteroidal CYP17A1 lyase inhibitor with good selectivity over CYP17A1 hydroxylase and CYPs 11B1 and 21A2 for the treatment of castration-resistant prostate cancer (CRPC) culminated in the discovery of BMS-351 (compound 18), a pyridyl biaryl benzimidazole with an excellent in vivo profile. Biological evaluation of BMS-351 at a dose of 1.5 mg in castrated cynomolgus monkeys revealed a remarkable reduction in testosterone levels with minimal glucocorticoid and mineralcorticoid perturbation. Based on a favorable profile, BMS-351 was selected as a candidate for further preclinical evaluation.

Entities:  

Keywords:  CYP11B1; CYP17A1; CYP21A2; Prostate cancer; benzimidazoles; cortisol; lyase

Year:  2015        PMID： 26819663      PMCID： PMC4716597          DOI： 10.1021/acsmedchemlett.5b00310

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  16 in total

1.  A general and efficient copper catalyst for the amidation of aryl halides and the N-arylation of nitrogen heterocycles.

Authors:  A Klapars; J C Antilla; X Huang; S L Buchwald
Journal:  J Am Chem Soc       Date:  2001-08-08       Impact factor: 15.419

2.  Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941.

Authors:  Charles Huggins; Clarence V Hodges
Journal:  J Urol       Date:  2002-07       Impact factor: 7.450

3.  EFFECT OF ORCHIECTOMY AND IRRADIATION ON CANCER OF THE PROSTATE.

Authors:  C Huggins
Journal:  Ann Surg       Date:  1942-06       Impact factor: 12.969

4.  Orteronel (TAK-700), a novel non-steroidal 17,20-lyase inhibitor: effects on steroid synthesis in human and monkey adrenal cells and serum steroid levels in cynomolgus monkeys.

Authors:  Masuo Yamaoka; Takahito Hara; Takenori Hitaka; Tomohiro Kaku; Toshiyuki Takeuchi; Junzo Takahashi; Satoru Asahi; Hiroshi Miki; Akihiro Tasaka; Masami Kusaka
Journal:  J Steroid Biochem Mol Biol       Date:  2012-01-12       Impact factor: 4.292

Review 5.  Medical strategies for treatment of castration resistant prostate cancer (CRPC) docetaxel resistant.

Authors:  Amelia Altavilla; Roberto Iacovelli; Giuseppe Procopio; Daniele Alesini; Emanuela Risi; Giuseppe Maria Campennì; Antonella Palazzo; Enrico Cortesi
Journal:  Cancer Biol Ther       Date:  2012-07-24       Impact factor: 4.742

Review 6.  Abiraterone in prostate cancer: a new angle to an old problem.

Authors:  Mark N Stein; Susan Goodin; Robert S Dipaola
Journal:  Clin Cancer Res       Date:  2012-03-26       Impact factor: 12.531

7.  Structural analysis of CYP2R1 in complex with vitamin D3.

Authors:  Natallia Strushkevich; Sergey A Usanov; Alexander N Plotnikov; Glenville Jones; Hee-Won Park
Journal:  J Mol Biol       Date:  2008-04-08       Impact factor: 5.469

8.  Effective testosterone suppression for prostate cancer: is there a best castration therapy?

Authors:  Leonard G Gomella
Journal:  Rev Urol       Date:  2009

9.  Copper-diamine-catalyzed N-arylation of pyrroles, pyrazoles, indazoles, imidazoles, and triazoles.

Authors:  Jon C Antilla; Jeremy M Baskin; Timothy E Barder; Stephen L Buchwald
Journal:  J Org Chem       Date:  2004-08-20       Impact factor: 4.354

Review 10.  New agents for the management of castration-resistant prostate cancer.

Authors:  Robert J Cersosimo
Journal:  Ann Pharmacother       Date:  2012-11-07       Impact factor: 3.154
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  2 in total

1.  Structure-Based Design of Inhibitors with Improved Selectivity for Steroidogenic Cytochrome P450 17A1 over Cytochrome P450 21A2.

Authors:  Charlie Fehl; Caleb D Vogt; Rahul Yadav; Kelin Li; Emily E Scott; Jeffrey Aubé
Journal:  J Med Chem       Date:  2018-05-24       Impact factor: 7.446

2.  Promising Tools in Prostate Cancer Research: Selective Non-Steroidal Cytochrome P450 17A1 Inhibitors.

Authors:  Silvia Bonomo; Cecilie H Hansen; Elyse M Petrunak; Emily E Scott; Bjarne Styrishave; Flemming Steen Jørgensen; Lars Olsen
Journal:  Sci Rep       Date:  2016-07-12       Impact factor: 4.379
  2 in total

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