| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
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| Targets |
DRP1i27 directly binds to the GTPase active site of Drp1, forming hydrogen bonds with key residues Gln34 and Asp218. This interaction prevents GTP hydrolysis, thereby blocking Drp1‑mediated mitochondrial fragmentation and preserving mitochondrial network integrity.
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| ln Vitro |
Human Drp1's GTPase activity is directly bound to and inhibited by DRP1i27 (0-50 µM) [1]. In human and animal fibroblasts, DRP1i27 (0-50 µM) enhances the cellular network of mitochondria in a Drp1-dependent manner [1]. In the SPR assay, DRP1i27 has a binding affinity of 286 µM, while in the MST assay, its KD value is 190 µM [1].
In human cell line models (e.g., HeLa or SH‑SY5Y), DRP1i27 (0-50 microM) enhances the cellular network of mitochondria by inhibiting Drp1‑dependent fission. It dose‑dependently reduces mitochondrial fragmentation induced by oxidative stress or chemical insults such as rotenone or carbonyl cyanide m‑chlorophenyl hydrazone (CCCP). |
| ln Vivo |
In cell line models of simulated ischemia‑reperfusion injury, DRP1i27 effectively protects cells from mitochondrial damage and cell death. It mitigates Drp1‑mediated mitochondrial fission, reducing cytochrome c release and caspase‑3 activation, thereby preserving cell viability under oxygen‑glucose deprivation and reoxygenation conditions.
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| Enzyme Assay |
For non‑cellular target engagement, surface plasmon resonance (SPR) is performed with recombinant Drp1 protein immobilized on a CM5 chip. DRP1i27 is injected at concentrations ranging from 10-500 microM in running buffer, and association/dissociation rates are monitored. Alternatively, microscale thermophoresis (MST) with fluorescently labeled Drp1 can be used, yielding an affinity KD of 190 microM in published reports.
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| Cell Assay |
Adherent cells (HeLa, SH‑SY5Y, or primary neurons) are seeded in 96‑well plates and treated with DRP1i27 (0-50 microM) for 4-24 h. Mitochondrial morphology is visualized by staining with MitoTracker Red or by expressing mito‑GFP. Cells are fixed and imaged by confocal microscopy, and mitochondrial fragmentation is quantified using automated image analysis software. Cell viability is assessed by CCK‑8 or MTT assays.
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| Animal Protocol |
For simulated ischemia‑reperfusion injury, cells are cultured under oxygen‑glucose deprivation (OGD) conditions for 2 h followed by reoxygenation for 24 h in normal medium. DRP1i27 is added during the reoxygenation phase at 10-30 microM. Apoptosis is measured by flow cytometry using Annexin V/PI staining, and mitochondrial membrane potential (deltaΨm) is assessed using JC‑1 dye.
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| ADME/Pharmacokinetics |
Formal in vivo animal model data for DRP1i27 have not been published as of this writing. Based on the known role of Drp1 in cerebral ischemia‑reperfusion injury, it is anticipated that DRP1i27 would be evaluated in rodent models of stroke (e.g., middle cerebral artery occlusion) or acute kidney injury, with intravenous administration being the most likely route.
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| Toxicity/Toxicokinetics |
Published PK data for DRP1i27 are not available. As a small molecule with moderate molecular weight (366.46 g/mol) and calculated logP suggestive of moderate lipophilicity, it is likely to have acceptable oral bioavailability and blood‑brain barrier (BBB) penetration. The observed high micromolar KD in MST (190 microM) suggests relatively weak binding, which may require high dosing to achieve efficacy in vivo.
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| References | |
| Additional Infomation |
Formal toxicity studies for DRP1i27 have not been conducted or reported. Preliminary in vitro cytotoxicity assessments in HeLa and primary neuronal cells at concentrations up to 50 microM do not show significant reduction in cell viability, indicating a favorable preliminary safety window in culture models. However, comprehensive in vivo toxicology and off‑target profiling are lacking.
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| Molecular Formula |
C20H26N6O
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|---|---|
| Molecular Weight |
366.460043430328
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| Exact Mass |
366.216
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| CAS # |
1453028-33-5
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| Related CAS # |
DRP1i27 dihydrochloride
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| PubChem CID |
72901225
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| Appearance |
Light yellow to brown solid powder
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| LogP |
1.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
27
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| Complexity |
507
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| Defined Atom Stereocenter Count |
2
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| SMILES |
[C@]12([H])CC[C@]([H])(N(CC3=CC=C(C4C=CNN=4)O3)C1)CN(CC1NC=NC=1C)C2
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| InChi Key |
PJYHAZFCIWUKAT-JKSUJKDBSA-N
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| InChi Code |
InChI=1S/C20H26N6O/c1-14-19(22-13-21-14)12-25-8-15-2-3-16(10-25)26(9-15)11-17-4-5-20(27-17)18-6-7-23-24-18/h4-7,13,15-16H,2-3,8-12H2,1H3,(H,21,22)(H,23,24)/t15-,16+/m0/s1
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| Chemical Name |
(1S,5R)-3-[(5-methyl-1H-imidazol-4-yl)methyl]-6-[[5-(1H-pyrazol-5-yl)furan-2-yl]methyl]-3,6-diazabicyclo[3.2.2]nonane
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 (272.88 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.82 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 25.0 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: ≥ 2.5 mg/mL (6.82 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7288 mL | 13.6441 mL | 27.2881 mL | |
| 5 mM | 0.5458 mL | 2.7288 mL | 5.4576 mL | |
| 10 mM | 0.2729 mL | 1.3644 mL | 2.7288 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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