| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
PD-1 (Programmed Cell Death Protein 1)/PD-L1 (Programmed Death-Ligand 1) immune checkpoint interaction; also functions as a Target Protein Ligand-Linker Conjugate for PROTAC applications.
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| ln Vitro |
One ligand is for an E3 ubiquitin ligase, and the other is for the target protein; these two ligands are joined by a linker to form PROTACs. The intracellular ubiquitin-proteasome system is utilized by PROTACs to specifically destroy target proteins[1].
This compound inhibits the PD-1/PD-L1 protein-protein interaction with an IC50 of 39.2 nM (HTRF binding assay). It functions as both a direct PD-1/PD-L1 interaction antagonist and a PROTAC building block. When incorporated into PROTAC molecules, it facilitates the recruitment of PD-1/PD-L1 to an E3 ubiquitin ligase for targeted degradation. It exhibits anti-cancer activity through immune checkpoint blockade. |
| ln Vivo |
No specific in vivo data. As a PD-1/PD-L1 inhibitor, it is expected to enhance T cell activation and anti-tumor immunity in syngeneic mouse models. When used in PROTAC PD-1/PD-L1 degrader-1, it may induce degradation of PD-L1 protein in tumor cells or tumor-associated macrophages, potentially offering superior activity compared to simple blockade by antagonizing PD-1/PD-L1 signaling and eliminating the target protein.
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| Enzyme Assay |
(1) Homogeneous Time-Resolved Fluorescence (HTRF) PD-1/PD-L1 binding assay: mix PD-1 tagged with Eu3+-cryptate, biotinylated PD-L1, streptavidin-XL665, and compound (serial dilutions 0.01 nM - 10 uM). (2) Incubate at room temperature for 2-3 hours. (3) Measure fluorescence at 620 nm (donor) and 665 nm (acceptor). (4) Calculate IC50 using ratio (665/620). (5) Control: use known PD-1/PD-L1 inhibitor (e.g., BMS-1166, IC50 1.4 nM).
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| Cell Assay |
(1) Co-culture PD-1-expressing Jurkat T cells with PD-L1-expressing antigen-presenting cells (or CHO cells). (2) Treat with compound (0.1 nM - 10 uM, 48-72 h). (3) Measure IL-2 production by ELISA in culture supernatant. (4) Alternatively, for T cell activation: isolate human PBMCs, stimulate with anti-CD3/anti-CD28, add PD-L1-Fc and compound, measure IFN-gamma by ELISA. (5) For PROTAC-based degradation: treat PD-L1-positive tumor cells with PROTAC PD-1/PD-L1 degrader-1 (0.1-1000 nM, 6-24 h), lyse, perform Western blot with anti-PD-L1 antibody.
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| Animal Protocol |
(1) For PD-1/PD-L1 inhibitor activity: use 6-8 week old female C57BL/6 mice bearing MC38 or B16-F10 tumors (100 mm3). (2) Administer compound IP or PO (1-100 mg/kg, daily or every other day). (3) Formulation: dissolve in 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline. (4) Monitor tumor volume for 14-21 days. (5) Endpoint: tumor weight, flow cytometry of TILs (CD8+/IFN-gamma+), ELISpot for T cell responses. For PROTAC degrader-1: similar dosing, then collect tumors for PD-L1 protein level analysis by IHC and Western blot.
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| ADME/Pharmacokinetics |
Standard formulation: 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline for IP/IV/IM/SC injection. Soluble in DMSO (100 mg/mL, 128.18 mM). PK of BMS-1166 parent: in mice, oral bioavailability ~40-60%, t1/2 ~ 3-6 h, Cmax and AUC dose-proportional (1-50 mg/kg). For PROTAC degrader-1 , PK typically: IP injection (10-50 mg/kg), Cmax ~ 0.5-2 uM, t1/2 ~ 2-4 h, moderate clearance.
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| Toxicity/Toxicokinetics |
For in vitro toxicity: CCK-8 on HEK293 cells (IC50 > 100 uM) and primary human hepatocytes. For in vivo toxicity: MTD study in CD-1 mice, single IP dose up to 200 mg/kg; observe for 14 days. Common findings at high doses: weight loss, lethargy, elevated ALT/AST (liver toxicity). The compound is intended for research use only, not for human use. This product is not FDA-approved.
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| References | |
| Additional Infomation |
BMS-1166-N-piperidine-CO-N-piperazine dihydrochloride is based on the potent PD-1/PD-L1 inhibitor BMS-1166 (IC50 1.4 nM). The piperidine-CO-piperazine extension provides a PROTAC linker handle, enabling direct incorporation into heterobifunctional PROTAC molecules. PROTAC PD-1/PD-L1 degrader-1 synthesized from this building block has shown efficacy in degrading PD-L1 protein in cancer cells, thereby blocking immune checkpoint signaling more effectively than small-molecule inhibitors alone. This dual functionality (direct inhibition + PROTAC building block) makes it valuable for immune-oncology research. Strictly for research use only.
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| Molecular Formula |
C41H44CL2N4O5
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|---|---|
| Molecular Weight |
743.717868804932
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| Exact Mass |
778.245
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| CAS # |
2691796-83-3
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| Related CAS # |
BMS-1166-N-piperidine-CO-N-piperazine;2447066-14-8
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| PubChem CID |
162646773
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
53
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| Complexity |
1160
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C=CC=C1C2=CC3=C(C=C2)OCCO3)COC4=C(C=C(C(=C4)OCC5=CC(=CC=C5)C#N)CN6CCCCC6C(=O)N7CCNCC7)Cl.Cl.Cl
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| InChi Key |
GHDAHXKKICFPOZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C41H43ClN4O5.2ClH/c1-28-32(8-5-9-34(28)31-11-12-37-40(22-31)49-19-18-48-37)27-51-39-23-38(50-26-30-7-4-6-29(20-30)24-43)33(21-35(39)42)25-46-15-3-2-10-36(46)41(47)45-16-13-44-14-17-45;;/h4-9,11-12,20-23,36,44H,2-3,10,13-19,25-27H2,1H3;2*1H
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| Chemical Name |
3-[[4-chloro-5-[[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]methoxy]-2-[[2-(piperazine-1-carbonyl)piperidin-1-yl]methyl]phenoxy]methyl]benzonitrile;dihydrochloride
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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 :~100 mg/mL (~128.18 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.20 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 (3.20 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3446 mL | 6.7230 mL | 13.4459 mL | |
| 5 mM | 0.2689 mL | 1.3446 mL | 2.6892 mL | |
| 10 mM | 0.1345 mL | 0.6723 mL | 1.3446 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.
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