| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Diacylglycerol kinase alpha (DGKalpha) and diacylglycerol kinase zeta (DGKzeta).
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|---|---|
| ln Vitro |
DGK-IN-1 inhibits DGKalpha with an IC50 of 0.65 uM and DGKzeta with an IC50 of 0.25 uM. By inhibiting these kinases, it prevents the conversion of diacylglycerol (DAG) to phosphatidic acid, leading to elevated intracellular DAG levels, which enhances the activation of protein kinase C (PKC) and other downstream effectors, thereby promoting T cell activation.
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| Enzyme Assay |
The standard DGK biochemical inhibition assay uses recombinant DGKalpha or DGKzeta enzymes. The assay mixture contains DGK-IN-1 dilutions, enzyme, a lipid substrate (e.g., DAG), and ATP. After incubation, the reaction product (phosphatidic acid) is detected and quantified using a homogeneous time-resolved fluorescence (HTRF) or ADP-Glo™ luminescence-based detection method. IC50 values are calculated from dose-response curves.
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| Cell Assay |
T cell activation assays are conducted using primary human T cells or Jurkat T cell lines. Cells are pre-treated with DGK-IN-1 and then stimulated with anti-CD3/CD28 antibodies. T cell activation markers such as IL-2 production (measured by ELISA), CD69 or CD25 expression (measured by flow cytometry), and T cell proliferation (measured by CFSE dilution or 3H-thymidine incorporation) are evaluated.
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| Animal Protocol |
In vivo activity is assessed in murine syngeneic tumor models. Immunocompetent mice (e.g., C57BL/6) are implanted with tumor cells (e.g., MC38 colon carcinoma or B16 melanoma). The compound is administered orally or intraperitoneally. Tumor growth is monitored, and T cell infiltration and activation in the tumor microenvironment are analyzed by flow cytometry and immunohistochemistry.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data are not publicly available but may be described in the patent WO2020006018A1. As a small molecule with molecular weight ~532 g/mol, its oral bioavailability, plasma half-life, and tissue distribution would need to be characterized in standard preclinical PK studies using rodents or dogs.
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| Toxicity/Toxicokinetics |
No detailed toxicology data are publicly available for DGK-IN-1. As a T cell activator, potential toxicities could include autoimmunity or cytokine release syndrome. Standard preclinical safety assessment would require in vitro cytotoxicity panels, hERG channel testing for cardiac safety, and repeat-dose toxicity studies in rodents.
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| References | |
| Additional Infomation |
DGK-IN-1 is a research chemical, not an approved drug. This compound represents a novel therapeutic strategy for cancer immunotherapy by targeting DGKalpha/zeta to enhance T cell function. It is one of the few small-molecule T cell activators that function by modulating lipid signaling pathways, bypassing the need for checkpoint blockade.
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| Molecular Formula |
C29H27CL2N5O
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|---|---|
| Molecular Weight |
532.46
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| Exact Mass |
531.159
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| CAS # |
2407892-34-4
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| PubChem CID |
146466342
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
5.5
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
37
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| Complexity |
881
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| Defined Atom Stereocenter Count |
2
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| SMILES |
N1C2=C(N(C)C(=O)C=C2N2C[C@@H](C)N(C(C3=CC=C(Cl)C=C3)C3=CC=C(Cl)C=C3)C[C@@H]2C)C=CC=1C#N
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| InChi Key |
REURPYMYAHZMMX-RBUKOAKNSA-N
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| InChi Code |
InChI=1S/C29H27Cl2N5O/c1-18-17-36(29(20-4-8-22(30)9-5-20)21-6-10-23(31)11-7-21)19(2)16-35(18)26-14-27(37)34(3)25-13-12-24(15-32)33-28(25)26/h4-14,18-19,29H,16-17H2,1-3H3/t18-,19+/m0/s1
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| Chemical Name |
8-[(2S,5R)-4-[bis(4-chlorophenyl)methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile
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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: 5 mg/mL (9.39 mM)
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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 | 1.8781 mL | 9.3904 mL | 18.7808 mL | |
| 5 mM | 0.3756 mL | 1.8781 mL | 3.7562 mL | |
| 10 mM | 0.1878 mL | 0.9390 mL | 1.8781 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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