| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
Target: Drp1 (dynamin-1-like protein, also known as DNM1L, IC50 = 0.91 uM). Drp1 is a large GTPase essential for mitochondrial and peroxisomal fission. By inhibiting Drp1, the compound blocks GTP hydrolysis, preventing the assembly of Drp1 oligomers around mitochondria and subsequent constriction, thereby preserving mitochondrial network integrity.
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|---|---|
| ln Vitro |
In vitro, Drp1-IN-1 (comp A-7) inhibits Drp1 GTPase activity with an IC50 of 0.91 uM in cell-free enzyme assays. It is reported to block mitochondrial fragmentation induced by various stressors, reduce cytochrome c release, and decrease apoptosis in cultured neuronal and cardiac cells exposed to oxidative stress or ischemia-reperfusion injury.
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| ln Vivo |
No in vivo efficacy data have been published specifically for Drp1-IN-1. However, Drp1 inhibitors in general have demonstrated in vivo efficacy in rodent models, including protection against myocardial ischemia-reperfusion injury, attenuation of acute kidney injury, reduced neuronal loss in models of Huntington's disease and traumatic brain injury, and suppression of tumor growth in cancer xenograft models.
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| Enzyme Assay |
For cell-free Drp1 GTPase inhibition assays: recombinant human Drp1 protein (GTPase domain) is incubated with varying concentrations of Drp1-IN-1 (0-100 uM), 1 mM GTP, and assay buffer. The reaction is carried out at 37degC for 30-60 min, and inorganic phosphate released from GTP hydrolysis is measured using a malachite green colorimetric assay or 32P-GTP thin-layer chromatography. IC50 values are calculated from dose-response curves.
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| Cell Assay |
For cell-based assays: cultured cells (e.g., HeLa, SH-SY5Y, H9c2 cardiomyocytes, primary neurons) are seeded in 96-well plates and treated with Drp1-IN-1 (1-50 uM, 2-24 h). Mitochondrial morphology is visualized by MitoTracker staining or immunofluorescence of outer mitochondrial membrane proteins (TOMM20). Image analysis (e.g., mitochondrial length, circularity, network fragmentation index) is performed using automated image analysis software to quantify Drp1 inhibition effects.
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| Animal Protocol |
No in vivo animal studies have been specifically reported for Drp1-IN-1. Potential future studies would involve rodent models (e.g., middle cerebral artery occlusion (MCAO) stroke model, myocardial ischemia-reperfusion model, cancer xenografts) where Drp1-IN-1 would be administered intraperitoneally or intravenously at doses of 5-20 mg/kg daily for 1-14 days, with assessment of mitochondrial morphology in harvested tissues, biochemical markers of apoptosis, and functional outcomes (infarct volume, neurological scores, tumor volume).
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| ADME/Pharmacokinetics |
No PK data are available for Drp1-IN-1. For small molecule Drp1 inhibitors (MW 448.54, solubility in DMSO 100 mg/mL), predicted PK properties in rodents: moderate oral bioavailability due to high molecular weight and lipophilicity, Tmax 1-2 h, plasma half-life 4-8 h. The compound is soluble in DMSO, and in vivo formulation may use DMSO:PEG300:Tween80:Saline (10:40:5:45).
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| Toxicity/Toxicokinetics |
No toxicity data have been reported for Drp1-IN-1. Based on its mechanism of action, Drp1 inhibition in normal cells may lead to mitochondrial elongation and fusion, which is generally well-tolerated at moderate doses. However, complete Drp1 ablation is embryonically lethal in mice, and long-term pharmacological inhibition could cause metabolic disturbances or impaired mitophagy. No acute toxicity studies have been published.
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| References | |
| Additional Infomation |
Drp1-IN-1 is a research compound not yet approved for clinical use. It is a valuable tool compound for studying mitochondrial fission and the role of Drp1 in various diseases, including cancer, cardiovascular disease (myocardial infarction, heart failure), neurodegenerative disorders (Alzheimer's, Parkinson's, Huntington's disease), and ischemia-reperfusion injury. It has potential as a lead compound for developing Drp1-targeted therapeutics but is currently in preclinical research only.
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| Molecular Formula |
C22H24N8OS
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|---|---|
| Molecular Weight |
448.543961524963
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| Exact Mass |
448.179
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| CAS # |
2247733-08-8
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| PubChem CID |
134817168
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.4
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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 |
6
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| Heavy Atom Count |
32
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| Complexity |
627
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1(CC2=CSC(N3CCCCC3)=N2)C=C(C)C=C1C(NC1=CC=C(C2=NNN=N2)C=C1)=O
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| InChi Key |
QNOOJEJAIFNEBQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H24N8OS/c1-15-11-19(21(31)23-17-7-5-16(6-8-17)20-25-27-28-26-20)30(12-15)13-18-14-32-22(24-18)29-9-3-2-4-10-29/h5-8,11-12,14H,2-4,9-10,13H2,1H3,(H,23,31)(H,25,26,27,28)
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| Chemical Name |
4-methyl-1-[(2-piperidin-1-yl-1,3-thiazol-4-yl)methyl]-N-[4-(2H-tetrazol-5-yl)phenyl]pyrrole-2-carboxamide
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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 (~222.95 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2295 mL | 11.1473 mL | 22.2946 mL | |
| 5 mM | 0.4459 mL | 2.2295 mL | 4.4589 mL | |
| 10 mM | 0.2229 mL | 1.1147 mL | 2.2295 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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