Linrodostat free base | BMS-986205 | CAS#1923833-60-6

MedKoo Cat#: 206817 | Name: BMS-986205

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

BMS-986205

CAS#1923833-60-6 (free base)

Theoretical Analysis

MedKoo Cat#: 206817

Name: BMS-986205

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

Chemical Formula: C24H24ClFN2O

Exact Mass: 410.1561

Molecular Weight: 410.92

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
10mg	USD 150.00	Ready to Ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship
500mg	USD 2,850.00	Ready to ship
1g	USD 4,650.00	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.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C8R06B05

QC Data

View QC data: current batch, Lot#C8R06B05

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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

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

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.

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:

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.

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.