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Purity: ≥98%
BMS-1166 is a novel and potent small molecule inhibitor of the PD-1/PD-L1 protein protein interaction with IC50 value of 1.6 nM in cell free assays. Bristol-Myers Squibb made the initial discovery. Monoclonal antibodies that block the PD-1/PD-L1 immune checkpoint pathway have significantly improved cancer treatment. The high cost of the antibodies, their short half-life, and immunogenicity are just a few drawbacks of antibody-based immunotherapies. The lack of complete structural knowledge for this pathway makes it difficult to develop small-molecule PD-1/PD-L1 inhibitors that could overcome these drawbacks. BMS-1001 and its analogs, the first chemical PD-1/PD-L1 inhibitors, were just revealed by Bristol-Myers Squibb.
| Targets |
PD-1/PD-L1 interaction (IC50 = 1.4 nM)
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| ln Vitro |
BMS-1166 exhibits low toxicity toward the tested cell lines and inhibits the interaction of soluble PD-L1 with PD-1 expressed on the cell surface. The T-cell receptor-mediated activation of T lymphocytes is inhibited by soluble PD-L1, but BMS-1166 reduces this effect[2].
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| Enzyme Assay |
BMS disclosed recently the first nonpeptidic small molecule inhibitors against the PD-1/PD-L1 pathway that showed the activity in a homogeneous time-resolved fluorescence (HTRF) binding assay; however no further data supporting their activity were provided.
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| References |
| Molecular Formula |
C36H33CLN2O7
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| Molecular Weight |
641.12
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| Exact Mass |
640.20
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| Elemental Analysis |
C, 67.44; H, 5.19; Cl, 5.53; N, 4.37; O, 17.47
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| CAS # |
1818314-88-3
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| Related CAS # |
BMS-1166 hydrochloride;2113650-05-6
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| Appearance |
Solid powder
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| SMILES |
CC1=C(C=CC=C1C2=CC3=C(C=C2)OCCO3)COC4=C(C=C(C(=C4)OCC5=CC(=CC=C5)C#N)CN6C[C@@H](C[C@@H]6C(=O)O)O)Cl
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| InChi Key |
QBXVXKRWOVBUDB-GRKNLSHJSA-N
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| InChi Code |
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
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| Chemical Name |
(2R,4R)-1-[[5-chloro-2-[(3-cyanophenyl)methoxy]-4-[[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]methoxy]phenyl]methyl]-4-hydroxypyrrolidine-2-carboxylic acid
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.24 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.24 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.24 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5598 mL | 7.7989 mL | 15.5977 mL | |
| 5 mM | 0.3120 mL | 1.5598 mL | 3.1195 mL | |
| 10 mM | 0.1560 mL | 0.7799 mL | 1.5598 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Structures and the PD-1/PD-L1 blocking potential of BMS compounds.Oncotarget.2017Aug 7;8(42):72167-72181. |
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Cytotoxicity and activity of BMS compounds in PD-1/PD-L1 checkpoint assay.Oncotarget.2017Aug 7;8(42):72167-72181. |
BMS compounds restore the sPD-L1-supressed activation of Jurkat T-cells.Oncotarget.2017 |
BMS-1166 induces binding cleft opening.Oncotarget.2017Aug 7;8(42):72167-72181. |
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Decomposition of BMS-1166.Oncotarget.2017Aug 7;8(42):72167-72181. |
he prediction of BMS-1001 and −1166 binding sites on PD-L1 surface.Oncotarget.2017Aug 7;8(42):72167-72181. |
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