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RU-SKI 43

CAS# 1043797-53-0

RU-SKI 43

Catalog No. BCC5441----Order now to get a substantial discount!

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Chemical structure

RU-SKI 43

3D structure

Chemical Properties of RU-SKI 43

Cas No. 1043797-53-0 SDF Download SDF
PubChem ID 90488982 Appearance Powder
Formula C22H30N2O2S M.Wt 386.55
Type of Compound N/A Storage Desiccate at -20°C
Synonyms Hhat Inhibitor
Solubility Soluble in DMSO > 10 mM
Chemical Name 2-(2-methylbutylamino)-1-[4-[(3-methylphenoxy)methyl]-6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl]ethanone;hydrochloride
SMILES CCC(C)CNCC(=O)N1CCC2=C(C1COC3=CC=CC(=C3)C)C=CS2.Cl
Standard InChIKey JBBKLHJLHRGJSQ-UHFFFAOYSA-N
Standard InChI 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
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

RU-SKI 43 Dilution Calculator

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RU-SKI 43 Molarity Calculator

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Preparing Stock Solutions of RU-SKI 43

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.587 mL 12.9349 mL 25.8699 mL 51.7397 mL 64.6747 mL
5 mM 0.5174 mL 2.587 mL 5.174 mL 10.3479 mL 12.9349 mL
10 mM 0.2587 mL 1.2935 mL 2.587 mL 5.174 mL 6.4675 mL
50 mM 0.0517 mL 0.2587 mL 0.5174 mL 1.0348 mL 1.2935 mL
100 mM 0.0259 mL 0.1293 mL 0.2587 mL 0.5174 mL 0.6467 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

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Background on RU-SKI 43

RU-SKI 43 is a small molecule inhibitor of Hhat(Hedgehog acyltransferase), the enzyme responsible for the attachment of palmitate onto Shh. IC50 value: Target: Hhat inhibitor RU-SKI 43 reduced pancreatic cancer cell proliferation and Gli-1 activation through Smoothened-independent non-canonical signaling. In addition, RU-SKI 43 treatment inhibited two key proliferative pathways regulated by Akt and mTOR.

References:
[1]. Petrova E, et al. Hedgehog acyltransferase as a target in pancreatic ductal adenocarcinoma. Oncogene. 2014 Jan 27. doi: 10.1038/onc.2013.575.

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References on RU-SKI 43

Single cell imaging and quantification of TDP-43 and alpha-synuclein intercellular propagation.[Pubmed:28373710]

Sci Rep. 2017 Mar 28;7(1):544.

The intercellular spreading of protein assemblies is a major factor in the progression of neurodegenerative disorders. The quantitative study and visualization of cell-to-cell propagation using tagged-proteins is challenging due to the steric effect of relatively large fluorescence tags and the risk of 'false positive' identification when analyzing these rare transmission events. Here, we established a cell culture model to characterize the cell-to-cell transmission of TAR DNA-binding protein and alpha-synuclein, involved in amyotrophic lateral sclerosis and Parkinson's disease, respectively, using the small nine amino acid influenza hemagglutinin tag. The novel use of single cell resolution imaging flow cytometry allowed the visualization and quantification of all individual transmission events. Cell-level analysis of these events indicated that the degree of transfer is lower than previously reported based on conventional flow cytometry. Furthermore, our analysis can exclude 'false positive' events of cellular overlap and extracellular debris attachment. The results were corroborated by high-resolution confocal microscopy mapping of protein localization.

TDP-43 and FUS en route from the nucleus to the cytoplasm.[Pubmed:28380257]

FEBS Lett. 2017 Jun;591(11):1489-1507.

Misfolded or mislocalized RNA-binding proteins (RBPs) and, consequently, altered mRNA processing, can cause neuronal dysfunction, eventually leading to neurodegeneration. Two prominent examples are the RBPs TAR DNA-binding protein of 43 kDa (TDP-43) and fused in sarcoma (FUS), which form pathological messenger ribonucleoprotein aggregates in patients suffering from amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two devastating neurodegenerative disorders. Here, we review the multiple functions of TDP-43 and FUS in mRNA processing, both in the nucleus and in the cytoplasm. We discuss how TDP-43 and FUS may exit the nucleus and how defects in both nuclear and cytosolic mRNA processing events, and possibly nuclear export defects, may contribute to neurodegeneration and ALS/FTD pathogenesis.

Depression and physical health multimorbidity: primary data and country-wide meta-analysis of population data from 190 593 people across 43 low- and middle-income countries.[Pubmed:28374652]

Psychol Med. 2017 Sep;47(12):2107-2117.

BACKGROUND: Despite the known heightened risk and burden of various somatic diseases in people with depression, very little is known about physical health multimorbidity (i.e. two or more physical health co-morbidities) in individuals with depression. This study explored physical health multimorbidity in people with clinical depression, subsyndromal depression and brief depressive episode across 43 low- and middle-income countries (LMICs). METHOD: Cross-sectional, community-based data on 190 593 individuals from 43 LMICs recruited via the World Health Survey were analysed. Multivariable logistic regression analysis was done to assess the association between depression and physical multimorbidity. RESULTS: Overall, two, three and four or more physical health conditions were present in 7.4, 2.4 and 0.9% of non-depressive individuals compared with 17.7, 9.1 and 4.9% among people with any depressive episode, respectively. Compared with those with no depression, subsyndromal depression, brief depressive episode and depressive episode were significantly associated with 2.62, 2.14 and 3.44 times higher odds for multimorbidity, respectively. A significant positive association between multimorbidity and any depression was observed across 42 of the 43 countries, with particularly high odds ratios (ORs) in China (OR 8.84), Laos (OR 5.08), Ethiopia (OR 4.99), the Philippines (OR 4.81) and Malaysia (OR 4.58). The pooled OR for multimorbidity and depression estimated by meta-analysis across 43 countries was 3.26 (95% confident interval 2.98-3.57). CONCLUSIONS: Our large multinational study demonstrates that physical health multimorbidity is increased across the depression spectrum. Public health interventions are required to address this global health problem.

Retinoic acid protects from experimental cerebral infarction by upregulating GAP-43 expression.[Pubmed:28380213]

Braz J Med Biol Res. 2017 Apr 3;50(4):e5561.

The aim of this study was to investigate whether exogenous retinoic acid (RA) can upregulate the mRNA and protein expression of growth-associated protein 43 (GAP-43), thereby promoting brain functional recovery in a rat distal middle cerebral artery occlusion (MCAO) model of ischemia. A total of 216 male Sprague Dawley rats weighing 300-320 g were divided into 3 groups: sham-operated group, MCAO+vehicle group and MCAO+RA group. Focal cortical infarction was induced with a distal MCAO model. The expression of GAP-43 mRNA and protein in the ipsilateral perifocal region was assessed using qPCR and immunocytochemistry at 1, 3, 7, 14, 21, and 28 days after distal MCAO. In addition, an intraperitoneal injection of RA was given 12 h before MCAO and continued every day until the animal was sacrificed. Following ischemia, the expression of GAP-43 first increased considerably and then decreased. Administration of RA reduced infarction volume, promoted neurological functional recovery and upregulated expression of GAP-43. Administration of RA can ameliorate neuronal damage and promote nerve regeneration by upregulating the expression of GAP-43 in the perifocal region after distal MCAO.

Description

RU-SKI 43 is a potent and selective Hedgehog acyltransferase (Hhat) inhibitor with an IC50 of 850 nM. RU-SKI 43 reduces Gli-1 activation through Smoothened-independent non-canonical signaling and decreases Akt and mTOR pathway activity. RU-SKI 43 has anti-cancer activity.

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