| Size | Price | Stock | Qty |
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| 25mg |
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| Targets |
GFB-8438 targets TRPC4 and TRPC5 channels, members of the transient receptor potential canonical (TRPC) family of non-selective cation channels. By inhibiting these channels, it modulates calcium influx and downstream signaling pathways. The compound shows equipotent activity against TRPC4 and TRPC5 with IC50 values of 0.29 μM and 0.18 μM, respectively.
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| ln Vitro |
GFB-8438 (1 μM) pretreatment of mouse podocytes for 30 min, followed by protamine sulfate incubation, substantially prevented synaptopodin loss and cytoskeletal remodeling[1].
In vitro, GFB-8438 potently inhibits hTRPC5 and hTRPC4 with IC50 values of 0.18 μM and 0.29 μM, respectively. It shows excellent selectivity over TRPC6 and other TRP family members. The compound protects mouse podocytes from injury induced by protamine sulfate in vitro. |
| ln Vivo |
In a hypertensive deoxycorticosterone acetate (DOCA)-salt rat model of focal segmental glomerulosclerosis (FSGS), GFB-8438 (30 mg/kg; sc; daily for 3 weeks) is effective in lowering both total protein and albumin concentrations in urine[1]. Cl, VSS, and t1/2 were 31 mL/min/kg, 1.17 L/kg, and 0.5 hours, respectively, following GFB-8438 (1 mg/kg; IV) treatment[1].
In vivo, GFB-8438 protects mouse podocytes from injury induced by protamine sulfate. The inhibition of TRPC5 may provide a novel, effective, and safe approach for the treatment of focal segmental glomerulosclerosis (FSGS) and related proteinuric kidney diseases. As a TRPC5 inhibitor, it can be administered to animal models of kidney disease to study its therapeutic potential. |
| Enzyme Assay |
In vitro assays for GFB-8438 typically involve measuring its inhibition of TRPC4 and TRPC5 channel activity. Cells expressing TRPC4 or TRPC5 are treated with increasing concentrations of the compound, and channel activity is measured using calcium influx assays with fluorescent calcium indicators or by electrophysiology. IC50 values are calculated from dose-response curves. Selectivity is confirmed by testing against other TRP channels and ion channels.
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| Cell Assay |
For in vitro cell-based assays, podocytes or other relevant cell lines are cultured and treated with GFB-8438 at various concentrations. The compound's protective effects against injury induced by protamine sulfate are assessed by measuring cell viability, cytoskeletal integrity, and apoptotic markers. Cell viability is assessed by standard assays.
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| Animal Protocol |
Animal/Disease Models: Sprague Dawley rats (DOCA-salt rat model of FSGS)[1]
Doses: 30 mg/kg Route of Administration: sc; daily for 3 weeks Experimental Results: Significant reduction in urine protein concentrations. Animal/Disease Models: 6-8 weeks old male SD rats[1] Doses: 1 mg/kg Route of Administration: iv (pharmacokinetic/PK Analysis) Experimental Results: The Cl, Vss, and t1/2 were 31 mL/min/kg, 1.17 L/kg, and 0.5 hrs (hours), respectively. In vivo animal studies with GFB-8438 are conducted in models of kidney disease, such as FSGS. The compound is administered orally or intraperitoneally at doses determined from pharmacokinetic studies. Kidney function is assessed by measuring proteinuria, serum creatinine, and blood urea nitrogen. Histopathological analysis of kidney tissues is performed. The compound's efficacy in protecting podocytes and reducing proteinuria has been demonstrated. |
| ADME/Pharmacokinetics |
GFB-8438 (CAS: 2304549-73-1) has a molecular weight of 386.76 g/mol and a molecular formula of C16H14ClF3N4O2. Chemical name: 4-Chloro-5-(3-oxo-4-(2-(trifluoromethyl)benzyl)piperazin-1-yl)pyridazin-3(2H)-one. Appearance: solid powder. Purity: ≥98%. Storage: -20°C. The compound is a potent TRPC5 inhibitor.
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| Toxicity/Toxicokinetics |
GFB-8438 is a research compound and is not approved for human therapeutic use. In preclinical studies, it has shown a manageable safety profile. As a TRPC5 inhibitor, it may have effects on calcium signaling in various tissues. The compound's selectivity over other TRP channels and ion channels may reduce off-target effects. Standard laboratory safety precautions should be followed.
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| References | |
| Additional Infomation |
GFB-8438 is a novel, potent, and subtype-selective TRPC inhibitor with IC50 values of 0.18 μM and 0.29 μM for hTRPC5 and hTRPC4, respectively. It shows excellent selectivity over TRPC6 and other TRP family members. It protects mouse podocytes from injury. It has a molecular weight of 386.76 g/mol and a molecular formula of C16H14ClF3N4O2. It is not FDA-approved and is intended for research use only.
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| Molecular Formula |
C₁₆H₁₄CLF₃N₄O₂
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|---|---|
| Molecular Weight |
386.7562
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| Exact Mass |
386.075
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| CAS # |
2304549-73-1
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| PubChem CID |
138471783
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.52±0.1 g/cm3(Predicted)
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| LogP |
2.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
26
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| Complexity |
650
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CN(C(=O)CN1C2=C(C(=O)NN=C2)Cl)CC3=CC=CC=C3C(F)(F)F
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| InChi Key |
MITRKIWBJVJRAM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H14ClF3N4O2/c17-14-12(7-21-22-15(14)26)23-5-6-24(13(25)9-23)8-10-3-1-2-4-11(10)16(18,19)20/h1-4,7H,5-6,8-9H2,(H,22,26)
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| Chemical Name |
4-chloro-5-(3-oxo-4-(2-(trifluoromethyl)benzyl)piperazin-1-yl)pyridazin-3(2H)-one
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| Synonyms |
GFB-8438 GFB 8438 GFB8438
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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 : ~83.33 mg/mL (~215.46 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.38 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.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.38 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 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.38 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 | 2.5856 mL | 12.9279 mL | 25.8558 mL | |
| 5 mM | 0.5171 mL | 2.5856 mL | 5.1712 mL | |
| 10 mM | 0.2586 mL | 1.2928 mL | 2.5856 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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