| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg | |||
| Other Sizes |
| Targets |
SCF; c-Kit
ISCK03 targets the c-Kit (CD117) receptor tyrosine kinase. It is a selective inhibitor of SCF/c-Kit signaling. By inhibiting c-Kit phosphorylation, ISCK03 blocks the activation of downstream signaling pathways, including the ERK pathway. This inhibition disrupts c-Kit-mediated cellular processes such as cell proliferation, survival, and differentiation. |
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| ln Vitro |
Pretreatment of 501mel cells with ISCK03 inhibits SCF-induced c-kit phosphorylation dose dependently. Additionally, ISCK03 prevents the phosphorylation of p44/42 ERK mitogen-activated protein kinase (MAPK), which is known to be connected to downstream signaling of SCF/c-kit. Nevertheless, ISCK03 is not able to prevent the phosphorylation of p44/42 ERK proteins caused by hepatocyte growth factor (HGF)[1]. CCDC26-KD cells cannot survive in low-serum environments when ISCK03, a tyrosine kinase inhibitor specific to KIT, is present. A dose-dependent sensitivity to ISCK03 is seen in all treated cells. Following ISCK03 treatment, KD cells experience the same level of survival suppression as non-KD cells. On the other hand, under circumstances of high serum concentration, ISCK03 treatment has minimal effects on the growth of control K562 and KD clone 3-5 cells[2].
ISCK03 inhibits SCF-induced c-Kit phosphorylation and downstream ERK phosphorylation in 501mel melanoma cells at concentrations of 1-5 µM. It also completely eliminates melanin synthesis in mice and brownish guinea pigs. The compound's activity is confirmed in cell-based assays where it inhibits c-Kit signaling at low micromolar concentrations. |
| ln Vivo |
Oral ISCK03 treatment causes newly regrown hair to depigment in a dose-dependent manner, which is reversed when the treatment is stopped. UV-induced hyperpigmented spots can be made to become less pigmented by applying ISCK03 topically. Epidermal melanin in areas treated with ISCK03 is reduced, according to Fontana-Masson staining analysis[1].
ISCK03 completely eliminates melanin synthesis in mice and brownish guinea pigs, demonstrating its in vivo efficacy in inhibiting c-Kit signaling. This effect is consistent with the role of c-Kit in melanocyte development and pigmentation. The compound's ability to inhibit c-Kit in vivo makes it a valuable tool for studying c-Kit-dependent processes in animal models. |
| Enzyme Assay |
Recombinant human c-kit protein is added for the kinase reaction, ATP is dispensed into 384-well plates, and chemical compounds (ISCK03: 2.5, 5, 10, 100 μM) are added by replicative plate. The development reaction is then allowed to run at room temperature for 40 minutes after a 45-minute incubation period at 37°C. The coumrain and fluorescein fluorescence-emission signals are detected after the reaction is stopped[1].
ISCK03 does not have a typical enzyme/receptor binding assay. Its activity is assessed in cell-based assays that measure its ability to inhibit c-Kit phosphorylation. Cells are treated with the compound and stimulated with SCF, and the level of c-Kit phosphorylation is measured by Western blot using phospho-specific antibodies. The inhibition of downstream ERK phosphorylation is also assessed. |
| Cell Assay |
In order to ascertain whether ISCK03 has any cytotoxic effects on 501mel cells, MTT assays are conducted utilizing varying doses of ISCK03 (1, 5, 10 μM). 501mel cells are cultured for 48 hours either with SCF with ISCK03 or with SCF alone (50 ng/mL)[1].
In vitro cellular assays for ISCK03 involve treating cells that express c-Kit, such as 501mel melanoma cells, with the compound. Cells are stimulated with SCF, and the phosphorylation of c-Kit and ERK is measured by Western blot. The compound's ability to inhibit these phosphorylation events is quantified to determine its potency. These assays confirm the compound's activity as a c-Kit inhibitor. |
| Animal Protocol |
Mice: The female C57BL/6 mice's backs are depilated in order to initiate the hair cycle. Mice under anesthesia have their hair briefly removed. Intraperitoneal injection of 50 mg of the rat antimouse c-kit-neutralizing monoclonal antibody ACK2 is done daily. One oral dose of ISCK03 is given each day. Animals are sacrificed or examined for repigmentation of the newly regrown hair shaft on days 21–28. For immunohistochemical analyses, skin is removed, frozen, and fixed in paraffin[1].
In vivo animal experiments for ISCK03 involve administering the compound to animal models to assess its effects on c-Kit-dependent processes. For example, the compound has been shown to completely eliminate melanin synthesis in mice and brownish guinea pigs. Its effects on pigmentation and other c-Kit-mediated processes can be evaluated in these models. |
| ADME/Pharmacokinetics |
ISCK03 has a molecular weight of 355.45 and a molecular formula of C19H21N3O2S. It is a cell-permeable compound, indicating that it can cross cell membranes to reach its intracellular target. Its solubility and stability are suitable for in vitro and in vivo research applications. The compound is typically used in research settings.
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| Toxicity/Toxicokinetics |
Toxicological data for ISCK03 is not detailed in the provided sources. As a research compound, it is not intended for human use. Standard safety precautions should be followed when handling. Its safety profile would need to be established through preclinical studies if it were to be developed for therapeutic applications.
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| References |
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| Additional Infomation |
ISCK03 is a cell-permeable, selective inhibitor of SCF/c-Kit signaling. It inhibits c-Kit phosphorylation and downstream ERK phosphorylation at low micromolar concentrations. The compound is used in cellular research into c-Kit-dependent signaling, pigmentation, and angiogenesis. It has been shown to completely eliminate melanin synthesis in mice and guinea pigs. It is available from various chemical suppliers for research purposes.
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| Molecular Formula |
C19H21N3O2S
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|---|---|
| Molecular Weight |
355.4539
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| Exact Mass |
355.135
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| Elemental Analysis |
C, 64.20; H, 5.96; N, 11.82; O, 9.00; S, 9.02
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| CAS # |
945526-43-2
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| Related CAS # |
945526-43-2
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| PubChem CID |
3792751
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
520.0±60.0 °C at 760 mmHg
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| Flash Point |
268.3±32.9 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
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| Index of Refraction |
1.607
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| LogP |
4.03
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
25
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| Complexity |
522
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=S(C1C=CC(C(C)(C)C)=CC=1)(NC1C=CC(N2C=CN=C2)=CC=1)=O
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| InChi Key |
XQABBHBFHWHMKF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H21N3O2S/c1-19(2,3)15-4-10-18(11-5-15)25(23,24)21-16-6-8-17(9-7-16)22-13-12-20-14-22/h4-14,21H,1-3H3
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| Chemical Name |
4-tert-butyl-N-(4-imidazol-1-ylphenyl)benzenesulfonamide
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| Synonyms |
ISCK03; ISCK 03; ISCK-03
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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: ~71 mg/mL (~199.8 mM)
Ethanol: ~3 mg/mL (~8.4 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.03 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 (7.03 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8133 mL | 14.0667 mL | 28.1334 mL | |
| 5 mM | 0.5627 mL | 2.8133 mL | 5.6267 mL | |
| 10 mM | 0.2813 mL | 1.4067 mL | 2.8133 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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