| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Ki: 0.22 μM (Hck)[1]
Hck (hematopoietic cell kinase), a Src family tyrosine kinase. iHCK-37 is a specific Hck inhibitor with a Ki of 0.22 uM. It binds to the ATP-binding pocket of Hck, blocking its kinase activity and downstream signaling pathways including PI3K/AKT and MAPK/ERK. |
|---|---|
| ln Vitro |
iHCK-37 (5.0 -20 μM; 24 hours) displays strong in vitro antiproliferative action. Growth inhibitory (GI50) values (μM) are 5.0-5.8 μM for AML cell lines (HL60, KG1a and U937) and 9.1-19.2 μM for chronic myelogenous leukemia cell lines (HEL and K562) [2]. iHCK-37 (3-9 μM; plus erythropoietin) results in reduced ERK, AKT, and P70S6K phosphorylation in lentivirally HCK-silenced K562 and U937 cell lines [2]. iHCK-37 (3-9 μM) causes a dose-dependent reduction in p-HCK, p-ERK, p-AKT, and p-70S6 in the cell line KG1a (AML/CD34+) [2].
iHCK-37 inhibits Hck with a Ki of 0.22 uM, making it a potent and specific Hck inhibitor. iHCK-37 blocks HIV-1 viral replication with an EC50 of 12.9 uM. In high Hck-expressing cells, iHCK-37 reduces PI3K/AKT and MAPK/ERK pathway activation after erythropoietin induction. It has been shown to have antitumor activity, likely through inhibition of Hck-mediated survival signaling in CML cells. |
| ln Vivo |
iHCK-37 has been studied for its ability to block HIV-1 viral replication. It reduces PI3K/AKT and MAPK/ERK pathway activation in high Hck-expressing cells, which may have implications for CML research. However, no detailed in vivo efficacy data are reported. It is primarily used as a research tool for in vitro studies of Hck function.
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| Enzyme Assay |
Cell-free Hck kinase activity assays are performed using recombinant human Hck enzyme. The enzyme is incubated with a peptide substrate and ATP in the presence of increasing concentrations of iHCK-37 (0.001-10,000 nM) in assay buffer (50 mM HEPES, pH 7.5, 10 mM MgCl2, 1 mM DTT). After 30-60 min at 30degC, the reaction is terminated, and Ki (0.22 uM) is determined by measuring phosphorylated substrate via luminescence (ADP-Glo) or 33P incorporation. Selectivity is assessed against other Src family kinases (e.g., Src, Lyn, Fyn) and unrelated kinases.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: U937, HL60, KG1a, HEL and K562 cells Tested Concentrations: 5.0-20 μM Incubation Duration: 24 hrs (hours) Experimental Results: demonstrated a reduction of growth in a dose-dependent manner. High Hck-expressing cell lines (e.g., certain CML cell lines) are seeded and treated with iHCK-37 at various concentrations (0.1-100 uM) for 24-72 hours. For Hck target engagement, cells are stimulated with erythropoietin (EPO) to activate Hck in the presence or absence of iHCK-37, and downstream signaling (PI3K/AKT, MAPK/ERK) is assessed by Western blot. For HIV-1 replication assays, HIV-1-infected cells are treated with iHCK-37, and viral replication is measured by p24 ELISA or qRT-PCR. Cell viability is assessed by MTT assay. EC50 for HIV-1 inhibition (12.9 uM) is determined. |
| Animal Protocol |
No specific in vivo animal protocols are published for iHCK-37. For potential in vivo studies, iHCK-37 would be formulated in a suitable vehicle (e.g., 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline) and administered to mice by intraperitoneal injection or oral gavage. For HIV-1 studies, humanized mice or transgenic mouse models would be used. For CML studies, xenograft models with Hck-expressing CML cells could be used. Efficacy would be assessed by tumor volume measurement, viral load, or pathway inhibition. No such studies are reported.
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| ADME/Pharmacokinetics |
No specific PK data are reported for iHCK-37. Molecular weight: 568.66 (C30H32N4O2S2) for the free base, 568.66 for the TFA salt? CAS 516478-09-4. Formula: C30H32N4O2S2 (free base). Solubility: DMSO (>10 mg/mL). Storage: -20degC, dry. PK parameters (t1/2, Cmax, AUC, oral bioavailability) have not been characterized. The compound may be used in in vitro assays at concentrations up to 100 uM. In vivo formulation requires co-solvents.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for iHCK-37. In cell-based assays at concentrations up to 100 uM, no overt cytotoxicity has been reported. As a Hck inhibitor, potential toxicities include effects on normal myeloid cell function. Standard safety assessments (hERG, Ames, repeat-dose toxicity) have not been performed. No clinical trials have been conducted. The compound is not FDA-approved. For research use only.
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| References |
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| Additional Infomation |
Other information: iHCK-37 (ASN05260065) (CAS 516478-09-4) is a research compound, not FDA-approved. It is a potent and specific Hck inhibitor with a Ki of 0.22 uM. It blocks HIV-1 viral replication (EC50 = 12.9 uM) and reduces PI3K/AKT and MAPK/ERK activation in high Hck-expressing cells. iHCK-37 is useful for studying Hck in CML, HIV-1 infection, and other diseases. Synonyms: ASN05260065. Purity ≥98%. For research use only.
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| Molecular Formula |
C30H32N4O2S2
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|---|---|
| Molecular Weight |
544.73
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| Exact Mass |
544.196
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| CAS # |
516478-09-4
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| PubChem CID |
3197505
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| Appearance |
White to off-white solid powder
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| LogP |
6.5
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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 |
8
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| Heavy Atom Count |
38
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| Complexity |
763
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(NC1=CC=CC=C1N1CCOCC1)(=O)CSC1N=C(CCC2=CC=CC=C2)N=C2SC3CCCCC=3C2=1
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| InChi Key |
YBVMBFMOYYGDEM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C30H32N4O2S2/c35-27(31-23-11-5-6-12-24(23)34-16-18-36-19-17-34)20-37-29-28-22-10-4-7-13-25(22)38-30(28)33-26(32-29)15-14-21-8-2-1-3-9-21/h1-3,5-6,8-9,11-12H,4,7,10,13-20H2,(H,31,35)
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| Chemical Name |
N-(2-morpholin-4-ylphenyl)-2-[[2-(2-phenylethyl)-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-yl]sulfanyl]acetamide
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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: 275 mg/mL (504.84 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.5 mg/mL (0.92 mM) (saturation unknown) in 10% DMSO + 10% Cremophor EL + 80% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Clear solution.
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 | 1.8358 mL | 9.1789 mL | 18.3577 mL | |
| 5 mM | 0.3672 mL | 1.8358 mL | 3.6715 mL | |
| 10 mM | 0.1836 mL | 0.9179 mL | 1.8358 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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