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Purity: ≥98%
BMS-1001 is a novel and potent small molecule inhibitor of the PD-1/PD-L1 protein protein interaction with IC50 value of 2.25 nM in cell free assays. By Bristol-Myers Squibb, it was first uncovered. Significant advancements in the treatment of cancer have been made possible by blocking the PD-1/PD-L1 immune checkpoint pathway with monoclonal antibodies. Numerous drawbacks of antibody-based immunotherapies include their immunogenicity, short half-lives, and high cost of the antibodies. Due to the lack of complete structural knowledge for this pathway, small-molecule PD-1/PD-L1 inhibitor development is slow and may not be able to address these issues. BMS-1001 and its analogs, the first chemically derived PD-1/PD-L1 inhibitors, were recently made public by Bristol-Myers Squibb.
| Targets |
PD-1/PD-L1 (EC50 = 253 nM)
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| ln Vitro |
BMS-1001 reduces the inhibition of T-cell receptor-mediated activation of T lymphocytes by soluble PD-L1. BMS-1001 is effective at reducing the PD-L1-associated cell surface protein's inhibitory effect.[1]
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| ln Vivo |
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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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| Cell Assay |
BMS-1001 reduces the inhibition of T-cell receptor-mediated activation of T lymphocytes by soluble PD-L1. The cell surface-associated PD-L1 inhibitory effect is successfully reduced by BMS-1001. [1] The ECs are stimulated with the anti-CD3 antibody in the presence of the recombinant human sPD-L1 in order to assess the effect of the BMS on the inhibition of T cells by soluble PD-L1. For this, 5 g/ml of the anti-CD3 antibody or the isotype control solution in PBS are coated onto the 96-well white flat bottom plates overnight at 4°C. After the plates have been dried and three PBS washes, the antibody solution is removed. In the presence of BMS-1001 or a corresponding volume of DMSO, PBS is supplemented with penicillin/streptomycin solution (100 U/ml final concentration each) and diluted with sPD-L1 (aa 18–134). The solution is then poured into each well of the antibody-coated plate in a volume of 15 μl. Before adding 60 μl of the cell solution to each well, ECs are centrifuged and diluted to 50 000 per ml. In its final state, sPD-L1 had a concentration of 10 μg/ml (0.6 μM). The final BMS-1001 concentrations are 0.12, 0.3, 1.2, and 3 μM, corresponding to the molar ratios of 1:5, 1:2, 2:1, and 5:1 between BMS and sPD-L1. Utilizing the Bio-Glo Luciferase Assay System, the cells are cultured for 24 hours before the luciferase activity assay is carried out.
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| References |
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| Molecular Formula |
C35H34N2O7
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| Molecular Weight |
594.65
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| Exact Mass |
594.24
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| Elemental Analysis |
C, 70.69; H, 5.76; N, 4.71; O, 18.83
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| CAS # |
2113650-03-4
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| Related CAS # |
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| PubChem CID |
131839624
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
44
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| Complexity |
957
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=CC(=C(C=C1OCC2=C(C(=CC=C2)C3=CC4=C(C=C3)OCCO4)C)OCC5=CC(=CC=C5)C#N)CN[C@H](CO)C(=O)O
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| InChi Key |
UWNXGZKSIKQKAH-SSEXGKCCSA-N
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| InChi Code |
InChI=1S/C35H34N2O7/c1-22-13-28(18-37-30(19-38)35(39)40)33(43-20-25-6-3-5-24(14-25)17-36)16-32(22)44-21-27-7-4-8-29(23(27)2)26-9-10-31-34(15-26)42-12-11-41-31/h3-10,13-16,30,37-38H,11-12,18-21H2,1-2H3,(H,39,40)/t30-/m1/s1
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| Chemical Name |
(2-((3-Cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methylbenzyl)-D-serine
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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) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6817 mL | 8.4083 mL | 16.8166 mL | |
| 5 mM | 0.3363 mL | 1.6817 mL | 3.3633 mL | |
| 10 mM | 0.1682 mL | 0.8408 mL | 1.6817 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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