| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Kinesin-1 (via KLC2-SKIP interaction). Kinesore inhibits the interaction between kinesin light chain 2 (KLC2) and SKIP (Ski-interacting protein), a cargo adaptor. The compound activates kinesin-1's function in controlling microtubule dynamics.
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| ln Vitro |
It is remarkable that the microtubule network was entirely rearranged into a network of rings and bundles in kinesore-treated cells. Moreover, lysosomal compartments are concentrated in juxtanuclear regions with a low microtubule count. This phenotype was very permeable at 50 μM kinesore; 95±2.4% (n=3, 200 cells total) of the cells had a rearranged non-radial microtubule network. This phenotype was observed in titration tests in cells treated for 1 hour at 25 μM kinesore concentrations; at 12.5 μM doses or lower, the effect was negligible. This impact is reversible since radial microtubule arrays are reconstituted once kinesore is washed out of cells treated with one hour and then for two hours. The microtubule network was shown to be reorganized by kinetin in a panel of cancer and normal mammalian cell lines. 50 μM kinesore causes the microtubule network to reorganize and large microtubule-rich projections to develop in wild-type cells. Kif5B mutant cells showed a substantial suppression of this phenotype, indicating that kinesin-1 is required for the microtubule remodeling caused by kinesore [1].
Kinesore inhibits KLC2-SKIP interaction with an IC50 of 101 µM and a Ki of 49 µM. At 50 µM, kinesore causes strong phenotypic effects with 95±2.4% penetrance (n=3). Kinesore causes the microtubule network to reorganize and large microtubule-rich projections to develop in wild-type cells. |
| ln Vivo |
Kinesore causes reorganization of the microtubule network and formation of large microtubule-rich projections in wild-type cells. Kif5B mutant cells show substantial suppression of this phenotype, indicating that kinesin-1 is required for the microtubule remodeling caused by kinesore. Detailed in vivo activity data in animal models has not been reported.
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| Enzyme Assay |
KLC2-SKIP interaction assay: Recombinant KLC2 and SKIP (or their interacting domains) are incubated with varying concentrations of Kinesore in binding buffer. The interaction is measured by surface plasmon resonance (SPR), fluorescence polarization, or AlphaScreen. IC50 and Ki values are calculated from dose-response curves.
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| Cell Assay |
Microtubule remodeling assay: Wild-type or Kif5B mutant cells are treated with Kinesore at 50 µM for a specified time (typically 1-24 hours). Cells are fixed and stained with anti-tubulin antibody to visualize microtubules by fluorescence microscopy. The percentage of cells showing microtubule reorganization and projection formation is quantified. The phenotype penetrance is calculated.
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| Animal Protocol |
No in vivo animal experimental protocols have been published for Kinesore in the available literature. In vivo studies would typically involve mouse models to evaluate the effects of kinesin-1 activation on neuronal transport, organelle trafficking, or microtubule dynamics, with compound administration via appropriate routes followed by histopathological and functional analyses.
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| ADME/Pharmacokinetics |
No pharmacokinetic data has been published in the available literature. Kinesore has CAS number 363571-83-9. Comprehensive PK parameters such as bioavailability, half-life, and plasma protein binding remain to be characterized. The compound is a small-molecule activator of kinesin-1.
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| Toxicity/Toxicokinetics |
No toxicity data has been published in the available literature. Kinesore is for research use only. Standard laboratory safety practices should be followed when handling this compound. As a modulator of microtubule dynamics, potential effects on cell division and intracellular transport should be considered.
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| References | |
| Additional Infomation |
3,5-Dibromo-N'-((2,5-dimethyl-1-(3-nitrophenyl)-1H-pyrrolo-3-yl)methylene)-4-hydroxybenzoylhydrazine is a regulator of kinesin-1.
Kinesore is a small molecule activator of kinesin-1 that inhibits KLC2-SKIP interaction with an IC50 of 101 µM. It activates kinesin-1's function in controlling microtubule dynamics, causing microtubule network reorganization and formation of microtubule-rich projections in cells. The phenotype requires kinesin-1 (Kif5B) function. No clinical trials or approved上市 status have been reported. |
| Molecular Formula |
C20H16BR2N4O4
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|---|---|
| Molecular Weight |
536.173442840576
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| Exact Mass |
533.953
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| CAS # |
363571-83-9
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| PubChem CID |
5349470
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.7±0.1 g/cm3
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| Index of Refraction |
1.689
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| LogP |
5.49
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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 |
4
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| Heavy Atom Count |
30
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| Complexity |
649
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| Defined Atom Stereocenter Count |
0
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| SMILES |
BrC1C(=C(C=C(C=1)C(N/N=C\C1C=C(C)N(C2C=CC=C(C=2)[N+](=O)[O-])C=1C)=O)Br)O
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| InChi Key |
DUGCMEGLYHBMAR-AUEPDCJTSA-N
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| InChi Code |
InChI=1S/C20H16Br2N4O4/c1-11-6-14(12(2)25(11)15-4-3-5-16(9-15)26(29)30)10-23-24-20(28)13-7-17(21)19(27)18(22)8-13/h3-10,27H,1-2H3,(H,24,28)/b23-10+
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| Chemical Name |
3,5-dibromo-N-[(E)-[2,5-dimethyl-1-(3-nitrophenyl)pyrrol-3-yl]methylideneamino]-4-hydroxybenzamide
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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 : ~125 mg/mL (~233.14 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (3.88 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8651 mL | 9.3254 mL | 18.6508 mL | |
| 5 mM | 0.3730 mL | 1.8651 mL | 3.7302 mL | |
| 10 mM | 0.1865 mL | 0.9325 mL | 1.8651 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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