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
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
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
Click here for help
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
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]