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1mg |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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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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Animal Protocol |
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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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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 | 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. th> |
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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. td> |
Structural Basis of the PD-1/PD-L1 (PD-L2) Interaction.Structure.2017 Aug 1;25(8):1163-1174. td> |
J Med Chem.2017Jul 13;60(13):5857-5867. th> |
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J Med Chem.2017Jul 13;60(13):5857-5867. |
J Med Chem.2017Jul 13;60(13):5857-5867. |