| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
ITPKB (inositol trisphosphate 3-kinase B, IC50 = 9 nM), ITPKA (IC50 = 20 nM), and ITPKC (IC50 = 19 nM). GNF362 is a highly selective, potent, and orally available inhibitor of the ITPK family of inositol phosphate kinases.
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| ln Vitro |
In lymphocytes, GNF362 (0–10 mM) inhibits Ins (1,3,4,5) P4 production, increases antigen receptor-driven Ca2+ responses, and triggers activated T cell apoptosis in an Itpkb-dependent manner[1]. After antigen receptor cross-linking, GNF362 increases SOC responses; in primary B or T lymphocytes, its EC50 is 12 nM[1].
GNF362 potently inhibits ITPKB with an IC50 of 9 nM and shows slightly lower potency against ITPKA (20 nM) and ITPKC (19 nM). It induces calcium influx in isolated mouse splenocytes (EC50 = 12 nM). GNF362 reverses the migratory stimulatory effects of ITPKA overexpression and overcomes TMZ (temozolomide) chemoresistance in cancer cells. |
| ln Vivo |
Orally administered GNF362 (6 or 20 mg/kg; twice daily; 21 days) inhibits the formation of antibodies to a modest degree, but at 6 mg/kg, it significantly lowers the infiltration of inflammatory cells into the joint, joint injury, and proteoglycan loss[1].
In vivo, GNF362 is orally active and has been shown to selectively delete donor alloreactive T-cells while preserving other immune functions. It overcomes TMZ chemoresistance in animal models of glioblastoma. By inhibiting ITPKB, GNF362 modulates intracellular calcium signaling and inositol phosphate metabolism, leading to altered T-cell activation and proliferation. |
| Enzyme Assay |
For non-cellular assays, recombinant ITPKA, ITPKB, or ITPKC enzyme is incubated with inositol 1,4,5-trisphosphate (IP3) and ATP in assay buffer. GNF362 is added at varying concentrations (0.1-1000 nM). The production of inositol 1,3,4,5-tetrakisphosphate (IP4) is measured by radiometric or mass spectrometry-based methods to calculate IC50 values.
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| Cell Assay |
For cell-based assays, T-cells or cancer cell lines are treated with GNF362 (1-100 nM) for 2-72 hours. Calcium influx is measured using fluorescent calcium indicators (e.g., Fluo-4 AM). T-cell proliferation is assessed by CFSE dilution, and activation markers (CD69, CD25) are quantified by flow cytometry. TMZ sensitivity is measured by MTT assays after co-treatment with GNF362.
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| Animal Protocol |
Animal/Disease Models: A Lewis rat antigen-induced arthritis (rAIA) model[1]
Doses: 6 or 20 mg/kg Route of Administration: Orally administration; 6 or 20 mg/kg; twice (two times) daily; 21 days Experimental Results: decreased knee swelling in both the 20mg/kg and 6mg/kg treatment groups of GNF362 by 47% and 34%, respectively. For animal studies, GNF362 is administered orally to mouse models (e.g., graft-versus-host disease models or glioblastoma xenografts). Doses typically range from 10-50 mg/kg once or twice daily. Alloreactive T-cell depletion is assessed by flow cytometry. Tumor growth is monitored, and TMZ resistance reversal is evaluated by survival analysis and tumor volume measurements. |
| ADME/Pharmacokinetics |
GNF362 is orally bioavailable with favorable pharmacokinetic properties. It is typically formulated in 0.5% methylcellulose or other oral vehicles for in vivo administration. Detailed PK parameters (half-life, Cmax, AUC) in preclinical species are available in the literature. The compound has a molecular weight of 426.44.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies have shown GNF362 to be well tolerated at therapeutic doses. No significant off-target toxicity or organ damage has been reported in animal studies. As an investigational research compound, it should be handled following standard safety protocols. It is not intended for human therapeutic use without further development.
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| References | |
| Additional Infomation |
GNF362 (CAS: 1003019-41-7) has a molecular formula of C22H21F3N6 and a molecular weight of 426.44. It is a highly selective ITPKB inhibitor that has shown promise in overcoming chemotherapy resistance. It is also used to study calcium signaling in lymphocytes and the role of inositol phosphate kinases in immune responses. It is not an approved drug.
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| Molecular Formula |
C22H21F3N6
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|---|---|
| Molecular Weight |
426.437554121017
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| Exact Mass |
426.177
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| CAS # |
1003019-41-7
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| PubChem CID |
57999583
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| Appearance |
White to off-white solid powder
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| LogP |
3.6
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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 |
4
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| Heavy Atom Count |
31
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| Complexity |
641
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| Defined Atom Stereocenter Count |
1
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| SMILES |
FC(C1=CN=C(C=C1)N1CCN(CC2C=NNC=2C2C=CC(C#N)=CC=2)C[C@H]1C)(F)F
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| InChi Key |
VNTCGXMLDSKOKN-OAHLLOKOSA-N
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| InChi Code |
InChI=1S/C22H21F3N6/c1-15-13-30(8-9-31(15)20-7-6-19(12-27-20)22(23,24)25)14-18-11-28-29-21(18)17-4-2-16(10-26)3-5-17/h2-7,11-12,15H,8-9,13-14H2,1H3,(H,28,29)/t15-/m1/s1
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| Chemical Name |
4-[4-[[(3R)-3-methyl-4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl]methyl]-1H-pyrazol-5-yl]benzonitrile
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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 (234.50 mM)
Ethanol: ≥ 50 mg/mL (117.25 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.86 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.86 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.88 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. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3450 mL | 11.7250 mL | 23.4500 mL | |
| 5 mM | 0.4690 mL | 2.3450 mL | 4.6900 mL | |
| 10 mM | 0.2345 mL | 1.1725 mL | 2.3450 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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