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Purity: ≥98%
BMS-8 is a novel small molecule inhibitor of the PD-1 (Programmed death-1)/PD-L1 (Programmed death-ligand 1) protein/protein interaction with potential anticancer activities. BMS-8 inhibits PD-1/PD-L1 interaction with an IC50 of 146 nM, and may augment therapeutic immune response to various histologically distinct tumors. Blockade of the PD-1/PD-Ll ligation using antibodies to PD-Ll has been shown to restore and augment T cell activation in many system. Structural basis for blocking the PD-1/PD-L1 interaction by small molecules is illustrated with the compound BMS-202 that binds to a hydrophobic cavity and induces dimerization of PD-L1.
| ln Vitro |
One of the PD-L1 monomers tends to have a more stable binding mode with BMS-8 than the other, and the small-molecule inducing PD-L1 dimerization was further stabilized by the non-polar interaction of Ile54, Tyr56, Met115, Ala121, and Tyr123 on both monomers and the water bridges involved in ALys124[2].
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| ln Vivo |
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| Enzyme Assay |
All binding studies are performed in an HTRF assay buffer consisting of dPBS supplemented with 0.1% (with v) bovine serum albumin and 0.05% (v/v) Tween-20. For the PD-l-Ig/PD-Ll-His binding assay, inhibitors are pre-incubated with PD-Ll-His (10 nM final) for 15 m in 4 μL of assay buffer, followed by addition of PD-l-Ig (20 nM final) in 1 μL of assay buffer and further incubation for 15 m. PD-L1 from either human, cyno, or mouse are used. HTRF detection is achieved using europium crypate-labeled anti- Ig (1 nM final) and allophycocyanin (APC) labeled anti-His (20 nM final). Antibodies are diluted in HTRF detection buffer and 5 μL is dispensed on top of binding reaction. The reaction mixture is allowed to equilibrate for 30 minutes and signal (665 nm/620 nm ratio) is obtained using an En Vision fluorometer. Additional binding assays are established between PD-1-Ig/PD-L2-His (20, 5 nM, respectively), CD80-His/PD-Ll-Ig (100, 10 nM, respectively) and CD80-His/CTLA4-Ig (10, 5 nM, respectively).
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| Cell Assay |
Particularly in a tumor microenvironment where lysis of tumor cells is a concern, the interaction between programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) plays a dominant role in the suppression of T cell responses. With an IC50 value of 18 nM, PD-1/PD-L1 inhibitor 2 is said to stop PD-L1 from interacting with PD-1.
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| References |
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| Molecular Formula |
C27H28BRNO3
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| Molecular Weight |
494.43
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| Exact Mass |
493.13
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| Elemental Analysis |
C, 65.59; H, 5.71; Br, 16.16; N, 2.83; O, 9.71
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| CAS # |
1675201-90-7
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| Related CAS # |
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| Appearance |
Solid powder
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| SMILES |
CC1=C(C=CC=C1C2=CC=CC=C2)COC3=C(C=C(C=C3)CN4CCCCC4C(=O)O)Br
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| InChi Key |
QRXBPPWUGITQLE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H28BrNO3/c1-19-22(10-7-11-23(19)21-8-3-2-4-9-21)18-32-26-14-13-20(16-24(26)28)17-29-15-6-5-12-25(29)27(30)31/h2-4,7-11,13-14,16,25H,5-6,12,15,17-18H2,1H3,(H,30,31)
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| Chemical Name |
1-[[3-bromo-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl]methyl]piperidine-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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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0225 mL | 10.1127 mL | 20.2253 mL | |
| 5 mM | 0.4045 mL | 2.0225 mL | 4.0451 mL | |
| 10 mM | 0.2023 mL | 1.0113 mL | 2.0225 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.
Structural Biology of the Immune Checkpoint Receptor PD-1 and Its Ligands PD-L1/PD-L2.Structure.2017 Aug 1;25(8):1163-1174. |
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New Directions in Designing the Therapeutics Targeting the PD-1/PD-L1 Interaction.Structure.2017 Aug 1;25(8):1163-1174. |
Structural Basis of the PD-1/PD-L1 (PD-L2) Interaction.Structure.2017 Aug 1;25(8):1163-1174. |
 J Med Chem.2017Jul 13;60(13):5857-5867. |
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