| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Programmed death-ligand 1 (PD-L1, CD274).
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|---|---|
| ln Vitro |
Compound 11c, PD-L1-IN-2, inhibits RKO cells with an IC50 value of 31.7μM[1]. In RKO cells, PD-L1 expression is inhibited by PD-L1-IN-2 (0-10 μM; 0-24 hours) in a way that is dependent on both dose and time [1]. PD-L1-IN-2 (0–10 μM; 0–24 hours) increases the turnover of the PD-L1 protein. The PD-L1 turnover rate in PD-L1-IN-2-treated cells was higher in CHX pulse chase compared to untreated cells[1].
PD-L1-IN-2 does not directly bind to PD-L1 or PD-1. Instead, it accelerates the turnover of the PD-L1 protein. In cellular assays, treatment with 0-10 microM PD-L1-IN-2 reduces the steady-state expression level of PD-L1 on the cell surface by promoting its degradation. |
| ln Vivo |
GPR84 antagonist 3 (compound 42) (ip; 25/50 mg/kg; once daily; 16 days) had a 45% inhibition rate in the 50 mg/kg group, suggesting that it can diminish tumor size. Compared to the PBS group, the group's average tumor weight was noticeably reduced[1].
In a colorectal cancer syngeneic mouse model (likely CT26), administration of PD-L1-IN-2 exerts anti-tumor effects. The mechanism is attributed to reduced PD-L1 expression in the tumor, which enhances tumor-infiltrating T-cell immunity. |
| Enzyme Assay |
A direct binding assay to PD-L1 is not relevant. Instead, a cellular PD-L1 expression assay is used. PD-L1-positive cells are treated with PD-L1-IN-2 (0-10 microM). The cells are then stained with an anti-PD-L1 antibody conjugated to a fluorophore and analyzed by flow cytometry to quantify the reduction in surface PD-L1.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: RKO cells Tested Concentrations: 5 μM Incubation Duration: 0h, 1h, 3h, 6h, 9h, 12h Experimental Results: Promoted the turnover of PD-L1 protein. CT26 cells (or other PD-L1+ cancer cells) are treated with PD-L1-IN-2 for 24 hours. Total cell lysates are prepared, and Western blotting is performed with an anti-PD-L1 antibody. A chase experiment with cycloheximide is used to demonstrate that the compound accelerates PD-L1 protein turnover. |
| Animal Protocol |
Animal/Disease Models: C57BL/6 mice with subcutaneous (sc) MC38 tumors[1]
Doses: 25/50 mg/kg Route of Administration: ip; 25/50 mg/kg; one time/day; 16 days Experimental Results: Suppressed MC38 tumor growth in vivo. For an efficacy study, 5×10^5 CT26 cells are implanted subcutaneously in Balb/c mice. After tumors reach 100 mm^3, the compound is administered at doses of 25-50 mg/kg (IP or oral) daily for 14 days. Tumor volume and body weight are monitored. |
| ADME/Pharmacokinetics |
As a small molecule, PD-L1-IN-2 (MW 586.68) likely exhibits good oral bioavailability. Its metabolic stability and half-life (t1/2) can be assessed by standard LC-MS/MS in rodent plasma. No specific human PK data is available for this preclinical agent.
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| Toxicity/Toxicokinetics |
Standard acute toxicity studies in rodents would be required for a full profile. Based on its mechanism of reducing PD-L1, a key immunosuppressive protein, it is expected to be well-tolerated with no severe acute toxicities reported in the available literature.
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| References | |
| Additional Infomation |
This compound is a research tool for studying the regulation of PD-L1 protein stability. Unlike antibodies or direct interaction inhibitors, it represents a novel class of PD-L1 inhibitors that modulate the protein's cellular half-life, offering a differentiated pharmacological approach.
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| Molecular Formula |
C33H38N4O6
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|---|---|
| Molecular Weight |
586.678028583527
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| Exact Mass |
586.279
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| CAS # |
2894733-91-4
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| PubChem CID |
168355652
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| Appearance |
White to off-white solid powder
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| LogP |
5.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
43
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| Complexity |
891
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)(C)OC(=O)NC1=CC=CC(=C1)C(=O)NC2=NC(=C(N2C)CC3=CC(=C(C=C3)OC)OC)CC4=CC=C(C=C4)OC
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| InChi Key |
WCBUHIGCYKSAAG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C33H38N4O6/c1-33(2,3)43-32(39)34-24-10-8-9-23(20-24)30(38)36-31-35-26(17-21-11-14-25(40-5)15-12-21)27(37(31)4)18-22-13-16-28(41-6)29(19-22)42-7/h8-16,19-20H,17-18H2,1-7H3,(H,34,39)(H,35,36,38)
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| Chemical Name |
tert-butyl N-[3-[[5-[(3,4-dimethoxyphenyl)methyl]-4-[(4-methoxyphenyl)methyl]-1-methylimidazol-2-yl]carbamoyl]phenyl]carbamate
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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: 50 mg/mL (85.23 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7045 mL | 8.5225 mL | 17.0451 mL | |
| 5 mM | 0.3409 mL | 1.7045 mL | 3.4090 mL | |
| 10 mM | 0.1705 mL | 0.8523 mL | 1.7045 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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