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linrodostat   Click here for help

GtoPdb Ligand ID: 9707

Synonyms: BMS-986205 | BMS986205 | Compound 2 [PMID: 29531094] | Example 19 [US20160137652A1]
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Linrodostat (BMS-986205) is a potent and selective, orally available indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor [3], being investigated as an immuno-therapeutic for various malignancies. The INN for linrodostat specifies the (R) stereoisomer. The chemical structure is claimed as example 19 in Flexus Bioscience's patent US2016137652 [1] and the compound is being taken through clinical development by Bristol-Myers Squibb. Mechanistically, linrodostat competes with the heme cofactor for binding to the apo-form of the enzyme, and once bound prevents heme from rebinding [3].

linrodostat is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 3
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 41.99
Molecular weight 410.16
XLogP 6.53
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES Clc1ccc(cc1)NC(=O)C(C1CCC(CC1)c1ccnc2c1cc(F)cc2)C
Isomeric SMILES Clc1ccc(cc1)NC(=O)[C@@H](C1CCC(CC1)c1ccnc2c1cc(F)cc2)C
InChI 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
InChI Key KRTIYQIPSAGSBP-KLAILNCOSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Beck HP, Jaen JC, Osipov M, Powers JP, Reilly MK, Shunatona HP, Walker JR, Zibinsky M, Balog JA, Williams DK et al.. (2016)
Immunoregulatory agents.
Patent number: US2016137652. Assignee: Flexus Biosciences, Inc.. Priority date: 05/11/2014. Publication date: 19/05/2016.
2. Li F, Zhang R, Li S, Liu J. (2017)
IDO1: An important immunotherapy target in cancer treatment.
Int Immunopharmacol, 47: 70-77. [PMID:28365507]
3. Nelp MT, Kates PA, Hunt JT, Newitt JA, Balog A, Maley D, Zhu X, Abell L, Allentoff A, Borzilleri R et al.. (2018)
Immune-modulating enzyme indoleamine 2,3-dioxygenase is effectively inhibited by targeting its apo-form.
Proc Natl Acad Sci USA, 115 (13): 3249-3254. [PMID:29531094]