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| Other Sizes |
Purity: ≥98%
| Targets |
PD-1/PD-L1 interaction
N-deacetylated BMS-202 targets the programmed death-1 (PD-1) and its ligand PD-L1 interaction. By blocking the binding of PD-1 to PD-L1, it restores and enhances T-cell-mediated anti-tumor immunity. It is a protein-protein interaction inhibitor with potential anticancer properties. |
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| ln Vitro |
N-deacetylated BMS-202, also known as PD1-PDL1 inhibitor 2, BMS 202, or BMS202, is a protein/protein interaction inhibitor with potential anticancer properties. It inhibits the PD-1 (Programmed Death-1)/PD-Ll (Programmed Death-ligand 1) protein/protein interaction. BMS-202 blocks the interaction between PD-1/PD-Ll and may improve the therapeutic immune response to various tumors with different histologies. Antibodies to PD-Ll have been shown to restore and enhance T cell activation in numerous systems by blocking the PD-1/PD-Ll ligation.
N-deacetylated BMS-202 inhibits the PD-1/PD-L1 interaction, potentially augmenting the therapeutic immune response to a number of histologically distinct tumors. As an inhibitor of this immune checkpoint pathway, it restores T cell function and enhances antitumor immune responses. Detailed IC50 values have been characterized in biochemical assays. |
| ln Vivo |
In vivo activity data for N-deacetylated BMS-202 are emerging. As a PD-1/PD-L1 inhibitor, it has potential utility in animal models of cancer. The compound's ability to restore T-cell-mediated antitumor immunity suggests that it could be effective in various tumor models. Further in vivo characterization is needed.
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| Enzyme Assay |
In an HTRF assay buffer, which consists of dPBS supplemented with 0.1% (with v) bovine serum albumin and 0.05% (v/v) Tween-20, all binding studies are carried out. In the PD-l-Ig/PD-Ll-His binding assay, the inhibitors are first pre-incubated with PD-Ll-His (10 nM final) for 15 m in 4 μL of assay buffer, and then PD-l-Ig (20 nM final) is added in 1 L of assay buffer and further incubated for 15 m. It is possible to use PD-L1 from mice, cyno, or humans. Allophycocyanin (APC) labeled anti-His (20 nM final) and anti-Ig (1 nM final) labeled with europium crypate are used to detect HTRF. HTRF detection buffer is used to dilute the antibodies, and 5 μL is dispensed on top of the binding reaction. After 30 minutes of equilibration, the reaction mixture is given another chance to settle, and an En Vision fluorometer is used to measure the signal (665 nm/620 nm ratio). Additional binding assays have been established between CD80-His/PD-Ll-Ig (100, 10 nM, respectively), CD80-His/CTLA4-Ig (10, 5 nM, respectively), and PD-1-Ig/PD-L2-His (20, 5 nM, respectively).
Cell-free assays for N-deacetylated BMS-202 typically utilize HTRF or AlphaScreen technologies to measure the PD-1/PD-L1 protein-protein interaction. Recombinant PD-1 and PD-L1 proteins are incubated with increasing concentrations of the compound. The inhibition of binding is quantified, and IC50 values are determined from concentration-response curves. |
| Cell Assay |
Particularly in a tumor microenvironment, the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) interaction dominates the suppression of T cell responses, preventing tumor cells from being lysed. With an IC50 value of 18 nM, PD-1/PD-L1 inhibitor 2 is said to prevent PD-L1 and PD-1 interaction.
Immune cells (e.g., primary human T cells) or cancer cells expressing PD-L1 are treated with N-deacetylated BMS-202 at various concentrations. T cell activation and proliferation are assessed by measuring cytokine production (e.g., IL-2, IFN-γ) or by CFSE dilution. PD-1/PD-L1 binding is assessed using flow cytometry or ELISA-based assays. |
| Animal Protocol |
In vivo animal studies for N-deacetylated BMS-202 are conducted in mouse syngeneic tumor models or human tumor xenografts in immunocompromised mice reconstituted with human immune cells. The compound is administered via oral or intraperitoneal routes. Tumor growth is measured over time, and immune cell infiltration and activation in the tumor microenvironment are assessed.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of N-deacetylated BMS-202 have not been comprehensively reported. As a small molecule (MW 377.48, formula C23H27N3O2), it is expected to have reasonable membrane permeability. The compound is soluble in DMSO. Detailed PK parameters remain to be determined.
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| Toxicity/Toxicokinetics |
Toxicity data for N-deacetylated BMS-202 are limited. As an immunomodulator targeting the PD-1/PD-L1 pathway, it has potential for immune-related adverse events similar to other checkpoint inhibitors. Standard toxicological assessments would be required for development.
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| References | |
| Additional Infomation |
N-deacetylated BMS-202 (molecular formula C23H27N3O2, MW 377.48) is the deacetylated derivative of BMS-202. It is a small-molecule inhibitor of the PD-1/PD-L1 protein-protein interaction that blocks the binding of PD-1 to its ligand PD-L1, restoring and enhancing T-cell-mediated anti-tumor immunity. The compound is intended for research use only.
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| Molecular Formula |
C23H27N3O2
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| Molecular Weight |
377.48
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| Exact Mass |
377.21032711
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| CAS # |
2310135-18-1
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| Related CAS # |
BMS-202;1675203-84-5
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| PubChem CID |
126843234
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| Appearance |
White to off-white solid
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| Density |
1.127±0.06 g/cm3(Predicted)
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| Boiling Point |
529.1±45.0 °C(Predicted)
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| LogP |
3.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
28
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| Complexity |
430
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C1C=CC(=C(N=1)OC)CNCCN)CC1C=CC=C(C2C=CC=CC=2)C=1C
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| InChi Key |
IVGJGWNPAKJGGB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H27N3O2/c1-17-20(9-6-10-21(17)18-7-4-3-5-8-18)16-28-22-12-11-19(15-25-14-13-24)23(26-22)27-2/h3-12,25H,13-16,24H2,1-2H3
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| Chemical Name |
N'-[[2-methoxy-6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl]methyl]ethane-1,2-diamine
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| Synonyms |
2310135-18-1; N'-[[2-methoxy-6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl]methyl]ethane-1,2-diamine; N1-((2-Methoxy-6-((2-methyl-[1,1'-biphenyl]-3-yl)methoxy)pyridin-3-yl)methyl)ethane-1,2-diamine; EX-A4442; N-deacetylated BMS-202
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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 |
| 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) |
DMSO: >33 mg/mL
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.62 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 25.0 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: ≥ 2.5 mg/mL (6.62 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 25.0 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: ≥ 2.5 mg/mL (6.62 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 | 2.6491 mL | 13.2457 mL | 26.4915 mL | |
| 5 mM | 0.5298 mL | 2.6491 mL | 5.2983 mL | |
| 10 mM | 0.2649 mL | 1.3246 mL | 2.6491 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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