| 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 serves as a Target Protein Ligand for PROTAC applications, enabling subsequent conjugation to E3 ligase ligands via linkers.
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| ln Vitro |
BMS-1166, the parent inhibitor, demonstrates potent inhibition of PD-1/PD-L1 interaction with an IC50 of 1.4 nM (HTRF binding assay). BMS-1166 antagonizes the inhibitory effect of the PD-1/PD-L1 immune checkpoint on T cell activation, thereby promoting T cell activation and anti-tumor immunity. BMS-1166-N-piperidine-COOH retains the BMS-1166 pharmacophore and provides a carboxyl handle for linker attachment to form PROTAC PD-1/PD-L1 degrader-1.
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| ln Vivo |
No direct in vivo data. As a BMS-1166-based moiety, it is expected to enhance T cell activation and anti-tumor immunity in syngeneic mouse models (e.g., MC38, CT26, B16-F10) at doses of 1-50 mg/kg PO or IP. When conjugated to an E3 ligase ligand via a linker (to form PROTAC degrader-1), it facilitates degradation of PD-L1 protein in addition to blocking the PD-1/PD-L1 interaction, potentially offering more durable and complete inhibition of this immune checkpoint pathway.
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| Enzyme Assay |
(1) Homogeneous Time-Resolved Fluorescence (HTRF) PD-1/PD-L1 binding assay: mix PD-1 (Eu3+-cryptate labeled), biotinylated PD-L1, streptavidin-XL665, and compound (0.001-1000 nM). (2) Incubate at 25degC for 2-3 hours. (3) Measure fluorescence at 620 nm and 665 nm; calculate IC50 from 665/620 ratio. (4) Control: use BMS-1166 (IC50 1.4 nM). BMS-1166-N-piperidine-COOH typically shows comparable IC50 (1-10 nM).
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| Cell Assay |
(1) Isolate human PBMCs from healthy donors. (2) Stimulate T cells with anti-CD3 (0.5 ug/mL) and anti-CD28 (1 ug/mL) in the presence of PD-L1-Fc fusion protein (1 ug/mL) and compound (0.1-1000 nM, 48 h). (3) Measure cytokine production (IL-2, IFN-gamma) by ELISA. (4) For PROTAC activity: treat PD-L1-positive tumor cells (e.g., MDA-MB-231, A375) with PROTAC degrader-1 (0.1-1000 nM, 6-24 h), lyse cells, perform Western blot with anti-PD-L1 antibody. (5) Assess PD-L1 degradation by densitometry normalized to GAPDH or beta-actin.
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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 colon carcinoma (100-150 mm3). (2) Administer BMS-1166-N-piperidine-COOH or the fully conjugated PROTAC degrader-1 IP or PO (5-50 mg/kg, daily or every other day for 14 days). (3) Formulation: dissolve in 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline. (4) Monitor tumor volume and body weight. (5) Endpoint: tumor weight, flow cytometry of TILs (CD8+, CD4+, Tregs), ELISA for serum IFN-gamma. (6) For degradation studies: collect tumors for PD-L1 IHC and Western blot.
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| ADME/Pharmacokinetics |
For BMS-1166 parent: in mice, oral bioavailability ~40-60%, t1/2 ~ 3-6 h, Cmax ~ 0.5-5 uM at 10 mg/kg PO. Standard formulation for in vivo studies: 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline for IP injection, or 0.5% methylcellulose + 0.2% Tween-80 for oral gavage. For PROTAC degrader-1 conjugates: PK typically includes moderate clearance (CL ~ 10-30 mL/min/kg) and moderate volume of distribution (Vd ~ 1-3 L/kg).
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| Toxicity/Toxicokinetics |
For in vitro toxicity: CCK-8 on HEK293 cells, IC50 typically >50 uM. For BMS-1166 parent: no significant in vivo toxicity at therapeutic doses (5-25 mg/kg). MTD studies in CD-1 mice: single IP dose up to 200 mg/kg, observe for 14 days; at 100 mg/kg IP, mild weight loss but no mortality. For PROTAC conjugates: monitor liver enzymes (ALT, AST) and kidney function (BUN, creatinine). The compound is intended for research use only, not for human therapeutic use.
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| References |
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| Additional Infomation |
BMS-1166-N-piperidine-COOH is derived from BMS-1166, a highly potent PD-1/PD-L1 inhibitor discovered by Bristol-Myers Squibb. The introduction of the piperidine-COOH group provides a chemical handle for conjugation to E3 ligase ligands (e.g., cereblon or VHL ligands) via standard amide coupling or using NHS ester activation. When conjugated to an E3 ligase ligand via an appropriate linker, it induces ubiquitination and proteasomal degradation of PD-L1 protein, thereby eliminating the immune checkpoint protein from the cell surface. This product has not received FDA approval and is strictly for research use only.
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| Molecular Formula |
C37H35CLN2O6
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|---|---|
| Molecular Weight |
639.14
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| Exact Mass |
638.218
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| CAS # |
2447066-00-2
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| PubChem CID |
118434619
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| Appearance |
White to off-white solid powder
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| LogP |
4.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
46
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| Complexity |
1040
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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)O)Cl
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| InChi Key |
RELGDHKISWTSBN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C37H35ClN2O6/c1-24-28(8-5-9-30(24)27-11-12-33-36(18-27)44-15-14-43-33)23-46-35-19-34(45-22-26-7-4-6-25(16-26)20-39)29(17-31(35)38)21-40-13-3-2-10-32(40)37(41)42/h4-9,11-12,16-19,32H,2-3,10,13-15,21-23H2,1H3,(H,41,42)
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| Chemical Name |
1-[[5-chloro-2-[(3-cyanophenyl)methoxy]-4-[[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]methoxy]phenyl]methyl]piperidine-2-carboxylic acid
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 1.5646 mL | 7.8230 mL | 15.6460 mL | |
| 5 mM | 0.3129 mL | 1.5646 mL | 3.1292 mL | |
| 10 mM | 0.1565 mL | 0.7823 mL | 1.5646 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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