Discovery and Preclinical Evaluation of BMS-986242, a Potent, Selective Inhibitor of Indoleamine-2,3-dioxygenase 1.


Journal

ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073

Informations de publication

Date de publication:
11 Feb 2021
Historique:
received: 20 12 2020
accepted: 22 01 2021
entrez: 19 2 2021
pubmed: 20 2 2021
medline: 20 2 2021
Statut: epublish

Résumé

Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing dioxygenase enzyme implicated in cancer immune response. This account details the discovery of BMS-986242, a novel IDO1 inhibitor designed for the treatment of a variety of cancers including metastatic melanoma and renal cell carcinoma. Given the substantial interest around this target for cancer immunotherapy, we sought to identify a structurally differentiated clinical candidate that performs comparably to linrodostat (BMS-986205) in terms of both

Identifiants

pubmed: 33603977
doi: 10.1021/acsmedchemlett.0c00668
pmc: PMC7883469
doi:

Types de publication

Journal Article

Langues

eng

Pagination

288-294

Informations de copyright

© 2021 American Chemical Society.

Déclaration de conflit d'intérêts

The authors declare no competing financial interest.

Références

Clin Cancer Res. 2005 Aug 15;11(16):6030-9
pubmed: 16115948
Cancer Res. 2015 Nov 1;75(21):4651-64
pubmed: 26363006
Nat Immunol. 2002 Nov;3(11):1097-101
pubmed: 12368911
Immunity. 2005 May;22(5):633-42
pubmed: 15894280
Mol Cancer Ther. 2020 Dec 9;:
pubmed: 33298590
J Am Chem Soc. 2018 Nov 7;140(44):14538-14541
pubmed: 30347977
Oncoimmunology. 2012 Dec 1;1(9):1460-1468
pubmed: 23264892
J Immunol. 2006 Jun 1;176(11):6752-61
pubmed: 16709834
J Med Chem. 2015 Dec 24;58(24):9421-37
pubmed: 25970480
J Med Chem. 2015 Nov 25;58(22):8762-82
pubmed: 26207924
J Med Chem. 2017 Dec 14;60(23):9617-9629
pubmed: 29111717
Oncotarget. 2014 Apr 30;5(8):2052-64
pubmed: 24903009
Proc Natl Acad Sci U S A. 2010 Nov 30;107(48):20768-73
pubmed: 21068375
Future Oncol. 2020 Jan;16(2):4359-4368
pubmed: 31823654
Immunol Rev. 2008 Apr;222:206-21
pubmed: 18364004
Front Immunol. 2014 Oct 20;5:521
pubmed: 25368620
Mol Cell Biol. 2014 Feb;34(3):428-38
pubmed: 24248597
Curr Cancer Drug Targets. 2007 Feb;7(1):31-40
pubmed: 17305476
Science. 2018 May 11;360(6389):588
pubmed: 29748264
Medchemcomm. 2017 May 16;8(7):1378-1392
pubmed: 30108849
Expert Opin Ther Targets. 2005 Aug;9(4):831-49
pubmed: 16083346
Eur J Med Chem. 2018 Jan 1;143:656-669
pubmed: 29220788
J Med Chem. 2019 Jul 25;62(14):6705-6733
pubmed: 31264862
Clin Cancer Res. 2015 Dec 15;21(24):5427-33
pubmed: 26519060
Eur J Cancer. 2012 Sep;48(13):2004-11
pubmed: 22033321
Clin Cancer Res. 2006 Feb 15;12(4):1144-51
pubmed: 16489067
Proc Natl Acad Sci U S A. 2018 Mar 27;115(13):3249-3254
pubmed: 29531094
J Invest Dermatol. 2010 Mar;130(3):898-901
pubmed: 19829303
J Neurochem. 1993 Mar;60(3):1159-62
pubmed: 7679723
J Biol Chem. 1978 Jul 10;253(13):4700-6
pubmed: 26687
J Neurooncol. 2015 Jul;123(3):395-403
pubmed: 25519303
J Clin Invest. 2004 Jul;114(2):280-90
pubmed: 15254595
Haematologica. 2008 Dec;93(12):1894-8
pubmed: 19050070
ACS Med Chem Lett. 2017 Mar 06;8(5):486-491
pubmed: 28523098
Front Oncol. 2018 Oct 04;8:423
pubmed: 30338242
Br J Cancer. 2012 Jan 3;106(1):141-7
pubmed: 22108515
Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2497-502
pubmed: 22308364
J Immunol. 2016 Jun 1;196(11):4487-97
pubmed: 27183624
Mol Cancer Res. 2019 Jan;17(1):131-139
pubmed: 30143553
Cancer Res. 2010 Jan 1;70(1):129-38
pubmed: 20028855
Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2611-6
pubmed: 16477023
Cancer Res. 2017 Dec 15;77(24):6795-6811
pubmed: 29247038
Eur J Immunol. 2007 Apr;37(4):1064-71
pubmed: 17343295
Lancet Oncol. 2019 Aug;20(8):1037-1039
pubmed: 31221617
J Med Chem. 2019 Oct 10;62(19):8784-8795
pubmed: 31525930
Amino Acids. 2014 Sep;46(9):2155-63
pubmed: 24875753

Auteurs

Emily C Cherney (EC)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Liping Zhang (L)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Susheel Nara (S)

Biocon BMS R&D Center, Bommasandra Jigani Link Rd, Bommasandra Industrial Area, Bengaluru, Karnataka 560099, India.

Xiao Zhu (X)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Johnni Gullo-Brown (J)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Derrick Maley (D)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Tai-An Lin (TA)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

John T Hunt (JT)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Christine Huang (C)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Zheng Yang (Z)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Celia Darienzo (C)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Lorell Discenza (L)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Asoka Ranasinghe (A)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Mary Grubb (M)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Theresa Ziemba (T)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Sarah C Traeger (SC)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Xin Li (X)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Kathy Johnston (K)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Lisa Kopcho (L)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Mark Fereshteh (M)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Kimberly Foster (K)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Kevin Stefanski (K)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Joseph Fargnoli (J)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Jesse Swanson (J)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Jennifer Brown (J)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Diane Delpy (D)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Steven P Seitz (SP)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Robert Borzilleri (R)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Gregory Vite (G)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Aaron Balog (A)

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Classifications MeSH