BMS-986205
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MedKoo CAT#: 206817

CAS#: 1923833-60-6 (free base)

Description: Linrodostat, also known as BMS-986205, ONO-7701 and F001287, a potent and selective, orally active IDO1 inhibitor with potential immunomodulating and antineoplastic activities. BMS-986205 specifically targets and binds to IDO1, a cytosolic enzyme responsible for the oxidation of the amino acid tryptophan into the immunosuppressive metabolite kynurenine. By inhibiting IDO1 and decreasing kynurenine in tumor cells, BMS-986205 restores and promotes the proliferation and activation of various immune cells, including dendritic cells (DCs), natural killer (NK) cells, and T lymphocytes, and causes a reduction in tumor-associated regulatory T cells (Tregs).

Chemical Structure

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BMS-986205
CAS# 1923833-60-6 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 206817
Name: BMS-986205
CAS#: 1923833-60-6 (free base)
Chemical Formula: C24H24ClFN2O
Exact Mass: 410.16
Molecular Weight: 410.917
Elemental Analysis: C, 70.15; H, 5.89; Cl, 8.63; F, 4.62; N, 6.82; O, 3.89

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to Ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1350 Ready to ship
500mg USD 2850 Ready to ship
1g USD 4650 Ready to ship
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Related CAS #: 1923833-60-6 (free base)   2221034-29-1 (mesylate)   1791396-46-7 (dimesylate )  

Synonym: BMS-986205; BMS 986205; BMS986205; ONO-7701; ONO 7701; ONO7701; F-001287; F001287; F001287; Linrodostat; NU 223618; NU 223618; NU-223618;

IUPAC/Chemical Name: (R)-N-(4-chlorophenyl)-2-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)propanamide

InChi Key: KRTIYQIPSAGSBP-ZACQAIPSSA-N

InChi Code: InChI=1S/C24H24ClFN2O/c1-15(24(29)28-20-9-6-18(25)7-10-20)16-2-4-17(5-3-16)21-12-13-27-23-11-8-19(26)14-22(21)23/h6-17H,2-5H2,1H3,(H,28,29)/t15-,16-,17+/m1/s1

SMILES Code: C[C@H]([C@H]1CC[C@@H](C2=CC=NC3=CC=C(F)C=C23)CC1)C(NC4=CC=C(Cl)C=C4)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: Activation of the immune system, which is suppressed in many cancers, may induce a cytotoxic T-lymphocyte (CTL) response against the IDO1-expressing tumor cells, thereby inhibiting the growth of IDO1-expressing tumor cells. IDO1, overexpressed by multiple tumor cell types, plays an important role in immunosuppression. Tryptophan depletion inhibits T-lymphocyte proliferation and activation, and subsequently suppresses the immune system.

Biological target: Emricasan (PF 03491390) is an orally active and irreversible pan-caspase inhibitor.
In vitro activity: Figure 7 shows that human cirrhotic hepatocytes cultured in vitro and treated with emricasan exhibit a marked amelioration in their phenotype when compared with vehicle‐treated cells, with improved expression of HNF4α, abcc3 and slc22a1, and higher albumin and urea synthesis, without signs of hepatotoxicity. The number of hepatocytes at the end of the experiment were not different between groups, as indicated by the amount of RNA obtained in each experimental condition. Interestingly, the beneficial effects of the drug were not observed in hepatocytes undergoing spontaneous de‐differentiation due to culture in conventional methods (data not shown). References: Hepatol Commun. 2019 Jul; 3(7): 987–1000. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601324/
In vivo activity: Mice fed a HFD diet demonstrate a five-fold increase in hepatocyte apoptosis by the TUNEL assay and a 1.5-fold and 1.3-fold increase in caspase-3 and-8 activities respectively; this increase in apoptosis was substantially attenuated in mice fed a HFD treated with Emricasan (HFD-Em). Likewise, liver injury and inflammation were reduced in mice fed HFD-Em as compare to HFD by measuring serum aspartate aminotransferase and alanine aminotransferase levels, NAS histological score and IL 1-β, TNF-α, monocyte chemoattractant protein (MCP-1) and C-X-C chemokine ligand-2 (CXCL2) quantitative reverse-transcription polymerase chain reaction (qPCR). These differences could not be attributed to differences in hepatic steatosis as liver triglycerides content were similar in both HFD groups. Hepatic fibrosis was reduced by Emricasan in HFD animals by decreasing αSMA (a marker for hepatic stellate cell activation), fibrosis score, Sirius red staining, hydroxyproline liver content and profibrogenic cytokines by qPCR. Reference: Liver Int. 2015 Mar;35(3):953-66. https://onlinelibrary.wiley.com/doi/abs/10.1111/liv.12570

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 42.0 73.75
Ethanol 100.0 175.59

Preparing Stock Solutions

The following data is based on the product molecular weight 410.92 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Gracia-Sancho J, Manicardi N, Ortega-Ribera M, Maeso-Díaz R, Guixé-Muntet S, Fernández-Iglesias A, Hide D, García-Calderó H, Boyer-Díaz Z, Contreras PC, Spada A, Bosch J. Emricasan Ameliorates Portal Hypertension and Liver Fibrosis in Cirrhotic Rats Through a Hepatocyte-Mediated Paracrine Mechanism. Hepatol Commun. 2019 Apr 22;3(7):987-1000. doi: 10.1002/hep4.1360. PMID: 31304452; PMCID: PMC6601324. 2. Xu M, Lee EM, Wen Z, Cheng Y, Huang WK, Qian X, Tcw J, Kouznetsova J, Ogden SC, Hammack C, Jacob F, Nguyen HN, Itkin M, Hanna C, Shinn P, Allen C, Michael SG, Simeonov A, Huang W, Christian KM, Goate A, Brennand KJ, Huang R, Xia M, Ming GL, Zheng W, Song H, Tang H. Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen. Nat Med. 2016 Oct;22(10):1101-1107. doi: 10.1038/nm.4184. Epub 2016 Aug 29. PMID: 27571349; PMCID: PMC5386783. 3. Barreyro FJ, Holod S, Finocchietto PV, Camino AM, Aquino JB, Avagnina A, Carreras MC, Poderoso JJ, Gores GJ. The pan-caspase inhibitor Emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis. Liver Int. 2015 Mar;35(3):953-66. doi: 10.1111/liv.12570. Epub 2014 Jun 6. PMID: 24750664. 4. Hoglen NC, Chen LS, Fisher CD, Hirakawa BP, Groessl T, Contreras PC. Characterization of IDN-6556 (3-[2-(2-tert-butyl-phenylaminooxalyl)-amino]-propionylamino]-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid): a liver-targeted caspase inhibitor. J Pharmacol Exp Ther. 2004 May;309(2):634-40. doi: 10.1124/jpet.103.062034. Epub 2004 Jan 23. PMID: 14742742.
In vitro protocol: 1. Gracia-Sancho J, Manicardi N, Ortega-Ribera M, Maeso-Díaz R, Guixé-Muntet S, Fernández-Iglesias A, Hide D, García-Calderó H, Boyer-Díaz Z, Contreras PC, Spada A, Bosch J. Emricasan Ameliorates Portal Hypertension and Liver Fibrosis in Cirrhotic Rats Through a Hepatocyte-Mediated Paracrine Mechanism. Hepatol Commun. 2019 Apr 22;3(7):987-1000. doi: 10.1002/hep4.1360. PMID: 31304452; PMCID: PMC6601324. 2. Xu M, Lee EM, Wen Z, Cheng Y, Huang WK, Qian X, Tcw J, Kouznetsova J, Ogden SC, Hammack C, Jacob F, Nguyen HN, Itkin M, Hanna C, Shinn P, Allen C, Michael SG, Simeonov A, Huang W, Christian KM, Goate A, Brennand KJ, Huang R, Xia M, Ming GL, Zheng W, Song H, Tang H. Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen. Nat Med. 2016 Oct;22(10):1101-1107. doi: 10.1038/nm.4184. Epub 2016 Aug 29. PMID: 27571349; PMCID: PMC5386783.
In vivo protocol: 1. Barreyro FJ, Holod S, Finocchietto PV, Camino AM, Aquino JB, Avagnina A, Carreras MC, Poderoso JJ, Gores GJ. The pan-caspase inhibitor Emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis. Liver Int. 2015 Mar;35(3):953-66. doi: 10.1111/liv.12570. Epub 2014 Jun 6. PMID: 24750664. 2. Hoglen NC, Chen LS, Fisher CD, Hirakawa BP, Groessl T, Contreras PC. Characterization of IDN-6556 (3-[2-(2-tert-butyl-phenylaminooxalyl)-amino]-propionylamino]-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid): a liver-targeted caspase inhibitor. J Pharmacol Exp Ther. 2004 May;309(2):634-40. doi: 10.1124/jpet.103.062034. Epub 2004 Jan 23. PMID: 14742742.

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1: Yuan L, Huang C, Liu-Kreyche P, Voronin K, Fancher RM, Allentoff A, Zheng N, Iyer R, Zhu L, Pillutla R, Ji QC. A convenient strategy to overcome interference in LC-MS/MS analysis: Application in a microdose absolute bioavailability study. J Pharm Biomed Anal. 2018 Dec 10;165:198-206. doi: 10.1016/j.jpba.2018.12.014. [Epub ahead of print] PubMed PMID: 30553110.

2: Pham KN, Yeh SR. Mapping the Binding Trajectory of a Suicide Inhibitor in Human Indoleamine 2,3-Dioxygenase 1. J Am Chem Soc. 2018 Nov 7;140(44):14538-14541. doi: 10.1021/jacs.8b07994. Epub 2018 Oct 24. PubMed PMID: 30347977.

3: Richards T, Brin E. Cell based functional assays for IDO1 inhibitor screening and characterization. Oncotarget. 2018 Jul 20;9(56):30814-30820. doi: 10.18632/oncotarget.25720. eCollection 2018 Jul 20. PubMed PMID: 30112109; PubMed Central PMCID: PMC6089395.

4: Cheong JE, Ekkati A, Sun L. A patent review of IDO1 inhibitors for cancer. Expert Opin Ther Pat. 2018 Apr;28(4):317-330. doi: 10.1080/13543776.2018.1441290. Epub 2018 Feb 23. Review. PubMed PMID: 29473428.

5: Blocking IDO1 Helps Shrink Bladder, Cervical Tumors. Cancer Discov. 2018 Jan;8(1):OF3. doi: 10.1158/2159-8290.CD-NB2017-167. Epub 2017 Nov 22. PubMed PMID: 29167110.