BMS-1166   Click here for help

GtoPdb Ligand ID: 9608

Synonyms: compound 2c [PMID: 28613862] | Example 1166 [WO2015160641A2]
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: BMS-1166 is a small molecule that disrupts the PD-1/PD-L1 immune checkpoint interaction. It is the most potent of the [3-(2,3-Dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]methanol derivatives described in [2], and it is claimed as Example 1166 in Bristol-Myers Squibb's patent WO2015160641A2 [1]. NMR analysis suggests that BMS-1166 promotes the formation of dimeric PD-L1 in solution.
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 5
Hydrogen bond donors 2
Rotatable bonds 10
Topological polar surface area 121.48
Molecular weight 640.2
XLogP 6.06
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 N#Cc1cccc(c1)COc1cc(OCc2cccc(c2C)c2ccc3c(c2)OCCO3)c(cc1CN1CC(CC1C(=O)O)O)Cl
Isomeric SMILES N#Cc1cccc(c1)COc1cc(OCc2cccc(c2C)c2ccc3c(c2)OCCO3)c(cc1CN1C[C@@H](C[C@@H]1C(=O)O)O)Cl
InChI InChI=1S/C36H33ClN2O7/c1-22-26(6-3-7-29(22)25-8-9-32-35(14-25)44-11-10-43-32)21-46-34-16-33(45-20-24-5-2-4-23(12-24)17-38)27(13-30(34)37)18-39-19-28(40)15-31(39)36(41)42/h2-9,12-14,16,28,31,40H,10-11,15,18-21H2,1H3,(H,41,42)/t28-,31-/m1/s1
InChI Key QBXVXKRWOVBUDB-GRKNLSHJSA-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. Chupak LS, Ding M, Martin SW, Zheng X, Hewawasam P, Connolly TP, Xu N, Yeung K-S, Zhu J, Langley DR, et al.. (2015)
Compounds useful as immunomodulators.
Patent number: WO2015160641A2. Assignee: Bristol-Myers Squibb Company. Priority date: 14/04/2014. Publication date: 22/10/2015.
2. Guzik K, Zak KM, Grudnik P, Magiera K, Musielak B, Törner R, Skalniak L, Dömling A, Dubin G, Holak TA. (2017)
Small-Molecule Inhibitors of the Programmed Cell Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) Interaction via Transiently Induced Protein States and Dimerization of PD-L1.
J Med Chem, 60 (13): 5857-5867. [PMID:28613862]
3. Skalniak L, Zak KM, Guzik K, Magiera K, Musielak B, Pachota M, Szelazek B, Kocik J, Grudnik P, Tomala M et al.. (2017)
Small-molecule inhibitors of PD-1/PD-L1 immune checkpoint alleviate the PD-L1-induced exhaustion of T-cells.
Oncotarget, 8 (42): 72167-72181. [PMID:29069777]