| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg | |||
| Other Sizes |
| Targets |
IC50: 850 nM (Hhat)[1]
RU-SKI 43 hydrochloride targets Hedgehog acyltransferase (Hhat) as a potent and selective inhibitor with an IC50 of 850 nM. Hhat is an enzyme that catalyzes the palmitoylation of the Hedgehog (Shh) protein, a critical step for Hedgehog signaling. By inhibiting Hhat, the compound blocks palmitoylation of Shh without affecting palmitoylation of H-Ras or Fyn, or myristoylation of c-Src. RU-SKI 43 hydrochloride reduces Gli-1 activation through Smoothened-independent non-canonical signaling and decreases Akt and mTOR pathway activity. |
|---|---|
| ln Vitro |
RU-SKI 43 hydrochloride (10 μM; for 6 days) greatly inhibits cell proliferation (83% in AsPC-1 cells) in AsPC-1 and Panc-1 cells[2]. RU-SKI 43 hydrochloride (10 or 20 μM; 5 hours) produces dose-dependent suppression of Shh palmitoylation following only 5 hours[1]. RU-SKI 43 hydrochloride (10 μM; for 72 hours) causes a 40% drop in Gli-1 levels in AsPC-1 cells[2] . RU-SKI 43 hydrochloride (10 μM; 48 hours) leads in reduced phosphorylation (47-67%) of four proteins in the Akt pathway, including Akt (phosphorylation at both Thr307 and Ser473), PRAS40, Bad and GSK-3β. RU-SKI 43 therapy also reduces phosphorylation of mTOR and S6, components of the mTOR signaling pathway[2]. RU-SKI 43 hydrochloride functions as an uncompetitive inhibitor (Ki=7.4 μM) with regard to Shh, and as a noncompetitive inhibitor ( Ki=6.9 μM) with respect to 125I-iodo-palmitoylCoA[1].
In vitro, RU-SKI 43 hydrochloride (10 μM; for 6 days) strongly decreases cell proliferation (83% in AsPC-1 cells) in AsPC-1 and Panc-1 cells. RU-SKI 43 hydrochloride (10 or 20 μM; 5 hours) causes dose-dependent inhibition of Shh palmitoylation. RU-SKI 43 hydrochloride (10 μM; for 72 hours) causes a 40% decrease in Gli-1 levels in AsPC-1 cells. RU-SKI 43 hydrochloride (10 μM; 48 hours) results in decreased phosphorylation (47-67%) of four proteins in the Akt pathway. It behaves as an uncompetitive inhibitor (Ki=7.4 μM) with respect to Shh and as a noncompetitive inhibitor (Ki=6.9 μM) with respect to 125I-iodo-palmitoylCoA. |
| ln Vivo |
After being administered intravenously, RU-SKI 43 hydrochloride has a t1/2 of 17 min in mouse plasma[1].
In vivo, RU-SKI 43 hydrochloride has a half-life (t1/2) of 17 minutes in mouse plasma after intravenous administration. In pancreatic cancer cells, it reduces both Gli1 activation and proliferation. The compound's ability to inhibit Hhat and reduce Gli-1 activation, combined with its effects on Akt and mTOR pathways, suggests potential for in vivo investigations of cancer, fibrosis, and TGF-β pathway-related diseases. Further research is ongoing to characterize its full in vivo efficacy profile. |
| Enzyme Assay |
For Hhat enzyme activity assays, recombinant Hhat enzyme is incubated with Shh peptide substrate, palmitoyl-CoA, and varying concentrations of RU-SKI 43 hydrochloride. Palmitoylation of Shh is measured using radioactive [125I]-iodo-palmitoylCoA or by mass spectrometry. IC50 values (850 nM) are calculated from dose-response curves. For kinetic studies, the compound's mode of inhibition (uncompetitive with respect to Shh, Ki=7.4 μM; noncompetitive with respect to palmitoylCoA, Ki=6.9 μM) is determined. Assays are performed in triplicate with appropriate vehicle controls.
|
| Cell Assay |
Cell Proliferation Assay[2]
Cell Types: AsPC-1 and Panc-1 pancreatic cancer cells Tested Concentrations: 10 μM Incubation Duration:For 6 days (drugs were replenished every 48 hrs (hours)) Experimental Results: Strongly diminished cell proliferation (83% in AsPC-1 cells). Western Blot Analysis[1] Cell Types: COS-1 cells expressing HA-Hhat and Shh Tested Concentrations: 10 or 20 μM Incubation Duration: 5 hrs (hours) Experimental Results: Caused dose-dependent inhibition of Shh palmitoylation following only 5 hrs (hours). For in vitro cellular assays, pancreatic cancer cell lines such as AsPC-1 and Panc-1 are cultured in appropriate media under standard conditions (37°C, 5% CO2). RU-SKI 43 hydrochloride is dissolved in DMSO and diluted in culture medium to desired concentrations (e.g., 10 μM). Cells are treated with compound for specified durations (e.g., 6 days for proliferation, 5 hours for palmitoylation, 72 hours for Gli-1 levels, 48 hours for Akt pathway). Cell proliferation is assessed by cell counting or MTT assays. Gli-1 levels and Akt pathway phosphorylation are measured by Western blot. Each concentration is tested in replicate wells with vehicle controls. |
| Animal Protocol |
For in vivo animal studies, RU-SKI 43 hydrochloride is typically formulated in suitable vehicles and administered via intravenous (i.v.) injection or oral gavage. The compound has a half-life of 17 minutes in mouse plasma after IV administration. Dosing regimens vary by study objective. In pancreatic cancer models, tumor growth and Gli-1 activation may be monitored. Blood and tissue samples may be collected for pharmacokinetic analysis. All procedures must follow institutional animal care and use committee guidelines.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of RU-SKI 43 hydrochloride indicate a short half-life of 17 minutes in mouse plasma after intravenous administration. The compound has a molecular weight of 423.01, formula C22H31ClN2O2S, and CAS number 1782573-67-4. Purity: >98%. Solubility: DMSO ≥51 mg/mL; H2O 2.5 mg/mL (ultrasonic). Storage: typically at -20°C for powder; in solvent at -80°C. Specific pharmacokinetic parameters such as clearance and volume of distribution are reported in the primary literature.
|
| Toxicity/Toxicokinetics |
According to available safety information, RU-SKI 43 hydrochloride is intended for research purposes only and is not for human use. Standard laboratory safety precautions should be followed when handling this compound, including the use of appropriate personal protective equipment (gloves, lab coat, safety goggles). The compound should be handled in a well-ventilated area. Avoid dust formation and inhalation. In case of skin contact, wash with plenty of soap and water. In case of eye contact, rinse cautiously with water for several minutes. No clinical toxicity data are available.
|
| References | |
| Additional Infomation |
RU-SKI 43 hydrochloride is a potent and selective Hhat inhibitor with an IC50 of 850 nM. It reduces Gli-1 activation and decreases Akt and mTOR pathway activity. It has a molecular weight of 423.01 and formula C22H31ClN2O2S. The compound is used to study TGF-β pathway regulation, fibrosis, and cancer progression. It is for research use only with no clinical development or regulatory approvals reported.
|
| Molecular Formula |
C22H31CLN2O2S
|
|---|---|
| Molecular Weight |
423.01
|
| Exact Mass |
422.179
|
| CAS # |
1782573-67-4
|
| Related CAS # |
RU-SKI 43;1043797-53-0
|
| PubChem CID |
90488982
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
28
|
| Complexity |
475
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CCC(C)CNCC(=O)N1CCC2=C(C1COC3=CC=CC(=C3)C)C=CS2.Cl
|
| InChi Key |
JBBKLHJLHRGJSQ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C22H30N2O2S.ClH/c1-4-16(2)13-23-14-22(25)24-10-8-21-19(9-11-27-21)20(24)15-26-18-7-5-6-17(3)12-18;/h5-7,9,11-12,16,20,23H,4,8,10,13-15H2,1-3H3;1H
|
| Chemical Name |
2-(2-methylbutylamino)-1-[4-[(3-methylphenoxy)methyl]-6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl]ethanone;hydrochloride
|
| HS Tariff Code |
2934.99.9001
|
| 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, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: ≥ 51 mg/mL (120.56 mM)
H2O: 2.5 mg/mL (5.91 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.91 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 (5.91 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 | 2.3640 mL | 11.8201 mL | 23.6401 mL | |
| 5 mM | 0.4728 mL | 2.3640 mL | 4.7280 mL | |
| 10 mM | 0.2364 mL | 1.1820 mL | 2.3640 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
