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Purity: ≥98%
PD1-PDL1 inhibitor 2 (also known as BMS-202, BMS 202, BMS202), is a novel and potent inhibitor of the PD-1 (Programmed death- 1)/PD-Ll (Programmed death-ligand 1) protein/protein interaction with potential antineoplastic activity. This information can be found in compound example 202 of patent WO/2015034820 A1. BMS-202 has good in vitro activity, with IC50 values of less than 50 nM in the cell-free assay, according to homogenous time-resolved fluorescence (HTRF) assay results. However, there are no known in vivo data for this compound. Small molecule BMS-202, which binds to and causes the dimerization of PD-L1, has a structural basis for blocking the PD-1/PD-L1 interaction.
Targets |
PD-1/PD-L1 (IC50 = 18 nM); PD-1/PD-L1 (KD = 8 μM)
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ln Vitro |
BMS-202 (0-100 μM; 4 days; SCC-3 or Jurkat cells) treatment prevents the proliferation of strongly PD-L1 positive SCC-3 cells (IC50 of 15 μM) and anti-CD3 antibody-activated Jurkat cells (IC50 10 μM) in vitro[2]. BMS-202 specifically induces PD-L1 thermal stabilization. BMS-202 causes PD-L1 dimerization in solution. At the homodimer's core, BMS-202 fills a large hydrophobic pocket, facilitating numerous additional interactions between the monomers. PD-1/PD-L1 interaction is physiologically mediated by hydrophobic surfaces, and BMS-202 interacts with both PD-L1 molecules on these surfaces[1].
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ln Vivo |
BMS-202 (20 mg/kg; intraperitoneal injection; daily; for 9 days; NOG-dKO mice) treatment exhibits a distinct antitumor effect in comparison to the controls, in humanized MHC- dKO NOG mice[2].
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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 |
The programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) interaction plays a dominant role in the suppression of T cell responses, especially in a tumor microenvironment, protecting tumor cells from lysis. PD-1/PD-L1 inhibitor 2 is reported to prevent the interaction of PD-L1 with PD-1 with an IC50 value of 18 nM.
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Animal Protocol |
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References |
Molecular Formula |
C25H29N3O3
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Molecular Weight |
419.52
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Exact Mass |
419.22
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Elemental Analysis |
C, 71.57; H, 6.97; N, 10.02; O, 11.44
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CAS # |
1675203-84-5
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Appearance |
Solid powder
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SMILES |
CC1=C(C=CC=C1C2=CC=CC=C2)COC3=NC(=C(C=C3)CNCCNC(=O)C)OC
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InChi Key |
JEDPSOYOYVELLZ-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C25H29N3O3/c1-18-22(10-7-11-23(18)20-8-5-4-6-9-20)17-31-24-13-12-21(25(28-24)30-3)16-26-14-15-27-19(2)29/h4-13,26H,14-17H2,1-3H3,(H,27,29)
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Chemical Name |
2-[2,6-dichloro-4-(3,5-dimethyl-1,2-oxazol-4-yl)anilino]-N-hydroxybenzamide
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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 | 2.3837 mL | 11.9184 mL | 23.8368 mL | |
5 mM | 0.4767 mL | 2.3837 mL | 4.7674 mL | |
10 mM | 0.2384 mL | 1.1918 mL | 2.3837 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.
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. |
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> |