| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
IC50: 4.6 nM (DGK α), 2.1nM (DGK ζ)[1].
Diacylglycerol kinase (DGK) α and ζ. BMS-502 is a potent dual inhibitor of DGKα and DGKζ, with IC50 values of 4.6 nM and 2.1 nM, respectively. DGKα and DGKζ are lipid kinases that phosphorylate diacylglycerol (DAG) to phosphatidic acid (PA), thereby regulating DAG-mediated signaling pathways involved in T cell activation. |
|---|---|
| ln Vitro |
The mouse cytotoxic T cell IFNγ assay (mCTC) yields an EC50 value of 340 nM for BMS-502 [1].
BMS-502 is a potent dual inhibitor of DGKα and DGKζ with IC50 values of 4.6 nM and 2.1 nM, respectively. It exhibits an EC50 value of 340 nM in the mouse cytotoxic T cell IFN-γ assay (mCTC). The compound induces cytokine release and T-cell proliferation consistent with DGK inhibition. It blocks intracellular checkpoint signaling in T cells. |
| ln Vivo |
In the mouse OT-1 model, BMS-502 (Compound 22) (0–10 mg/kg; oral; 24 hours) shows dose-dependent immunostimulatory effects[1]. Route Dose (mg/kg) AUClast (μM·h) t1/2 (h) Tmax (h) Cmax (μM) Cl (m/min/kg) Vss (mL/ kg) F (%) iv 1 14.8 22.5 / / 1.9 3.9 / po 5 48 / 3.0 1.08 / / 65 is the pharmacokinetic analysis of C57 in mice.
In vivo, BMS-502 (0.3-10 mg/kg) increases the frequency of CD69+CD8+ T cells when administered in combination with the peptide antigen SIINFEKL in OT-I mice. It demonstrates dose-dependent immune stimulation in the mouse OT-I model. The compound potentiates an immune response in human and mouse T-cells. |
| Enzyme Assay |
In vitro enzyme activity assays for BMS-502 involve measuring its ability to inhibit DGKα and DGKζ kinase activity. Recombinant DGK enzymes are incubated with diacylglycerol substrate in the presence of ATP and increasing concentrations of the compound. Kinase activity is measured by detecting the production of phosphatidic acid, and IC50 values are determined.
|
| Cell Assay |
In vitro cellular assays for BMS-502 involve treating T cells with the compound and measuring its effects on T cell activation and cytokine production. Readouts include IFN-γ production (mCTC assay, EC50 = 340 nM), T-cell proliferation, and cytokine release. The compound's ability to block intracellular checkpoint signaling is also assessed.
|
| Animal Protocol |
Animal/Disease Models: OT-1 mouse model[1]
Doses: 0-10 mg/kg Route of Administration: Oral administration; 24 h Experimental Results: Caused no significant increase in activated effector T-cells. In vivo efficacy of BMS-502 is evaluated in the mouse OT-I model. The compound is administered at doses of 0.3-10 mg/kg. Efficacy endpoints include the frequency of CD69+CD8+ T cells. The compound potentiates immune responses and demonstrates dose-dependent immune stimulation. |
| ADME/Pharmacokinetics |
BMS-502 has a molecular weight of 516.50 g/mol and a molecular formula of C27H22F2N6O3. Its IUPAC name is 8-(4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)-5-methyl-7-nitro-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile. It is soluble in DMSO (25 mg/mL) and has a purity of 99.49%.
|
| Toxicity/Toxicokinetics |
No specific toxicity data is available for BMS-502 in the provided literature. As a therapeutic candidate for cancer immunotherapy, its safety profile would be an important consideration. Potential toxicities could be related to its immunomodulatory effects. Standard preclinical safety studies would be required.
|
| References | |
| Additional Infomation |
BMS-502 is a potent dual inhibitor of DGKα and DGKζ with IC50 values of 4.6 nM and 2.1 nM, respectively. It activates T cells and potentiates immune responses. BMS-502 demonstrates dose-dependent immune stimulation in the mouse OT-I model and can be used in tumor immunity-related research. It has a molecular formula of C27H22F2N6O3 and a molecular weight of 516.50.
|
| Molecular Formula |
C27H22F2N6O3
|
|---|---|
| Molecular Weight |
516.498792171478
|
| Exact Mass |
516.172
|
| CAS # |
2407854-18-4
|
| PubChem CID |
146466271
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
3.6
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
38
|
| Complexity |
949
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CN1C2=C(C(=C(C1=O)[N+](=O)[O-])N3CCN(CC3)C(C4=CC=C(C=C4)F)C5=CC=C(C=C5)F)N=C(C=C2)C#N
|
| InChi Key |
XAHMIJCNFUSTMT-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C27H22F2N6O3/c1-32-22-11-10-21(16-30)31-23(22)25(26(27(32)36)35(37)38)34-14-12-33(13-15-34)24(17-2-6-19(28)7-3-17)18-4-8-20(29)9-5-18/h2-11,24H,12-15H2,1H3
|
| Chemical Name |
8-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]-5-methyl-7-nitro-6-oxo-1,5-naphthyridine-2-carbonitrile
|
| HS Tariff Code |
2934.99.9001
|
| 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, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: 1 mg/mL (1.94 mM)
|
|---|---|
| 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 | 1.9361 mL | 9.6805 mL | 19.3611 mL | |
| 5 mM | 0.3872 mL | 1.9361 mL | 3.8722 mL | |
| 10 mM | 0.1936 mL | 0.9681 mL | 1.9361 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
