| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
SH-42 specifically targets human delta24-dehydrocholesterol reductase (DHCR24), an enzyme encoded by the DHCR24 gene. This enzyme is responsible for the final step in the cholesterol biosynthesis pathway, converting desmosterol to cholesterol by reducing the delta24 double bond. Inhibition of DHCR24 by SH-42 results in the accumulation of its substrate desmosterol and a corresponding decrease in cholesterol levels within cells and plasma. DHCR24 has also been implicated in neuroprotection and cell survival, making it a potential target for diseases like Alzheimer's disease and certain cancers. By selectively inhibiting DHCR24 with nanomolar potency, SH-42 enables researchers to dissect the distinct biological roles of cholesterol and desmosterol in various physiological and pathological processes.
|
|---|---|
| ln Vitro |
In vitro studies demonstrate that SH-42 is a highly potent and selective inhibitor of DHCR24. The compound exhibits an IC₅0 of 42 nM against human DHCR24 in cell-free enzyme assays. For comparison, a similar inhibitor has been reported with an IC₅0 of 4.2 nM, indicating the high sensitivity of this target to inhibition. SH-42 shows minimal activity against other enzymes in the cholesterol biosynthetic pathway and across other metabolic enzymes, confirming its selectivity for DHCR24. Cellular studies using human cell lines (e.g., HepG2 hepatocytes or neuroblastoma cells) treated with SH-42 show a dose-dependent accumulation of desmosterol and reduction in cholesterol levels, as measured by LC-MS or GC-MS analysis of lipid extracts. At concentrations of 0.1-10 uM, SH-42 alters sterol composition without causing significant cytotoxicity.
|
| ln Vivo |
In vivo studies in mice demonstrate that SH-42 effectively inhibits DHCR24 activity and leads to a significant increase in plasma desmosterol levels. Following administration, animals show elevated desmosterol concentrations, confirming target engagement in vivo. Although detailed efficacy studies are limited, related DHCR24 inhibitors have shown that plasma desmosterol can increase up to 10-fold after treatment. The compound has been tested in mouse models to investigate the role of desmosterol accumulation in various disease contexts, including neurological disorders and liver disease. SH-42 is typically administered via intraperitoneal injection or oral gavage. The compound's ability to cross the blood-brain barrier may be of particular interest for studying desmosterol's neuroprotective effects. Further in vivo studies are needed to evaluate the functional consequences of DHCR24 inhibition on whole-body cholesterol homeostasis and disease progression.
|
| Enzyme Assay |
In vitro DHCR24 activity is measured using a radiometric or LC-MS-based enzyme assay. The standard protocol involves incubating human DHCR24 enzyme (either recombinant or from tissue lysates) with its substrate desmosterol (typically radiolabeled [3H]-desmosterol) in the presence of NADPH as a cofactor. SH-42, dissolved in DMSO, is added at various concentrations (0.1-1000 nM) to the reaction mixture. After incubation at 37degC for 30-60 minutes, the reaction is terminated, and the product (cholesterol) is separated from the substrate by thin-layer chromatography (TLC) or solid-phase extraction. The amount of product is quantified by liquid scintillation counting for radiolabeled assays or by LC-MS/MS for unlabeled assays. The IC₅0 is calculated by plotting inhibition percentage against the log concentration of SH-42 and fitting to a four-parameter logistic model. For selectivity profiling, the compound is tested against other cholesterol biosynthesis enzymes (e.g., DHCR7, CYP51) and a panel of 50+ metabolic enzymes.
|
| Cell Assay |
Cellular DHCR24 inhibition can be assessed using sterol profiling by LC-MS. Cells (e.g., HepG2, HEK293, or SH-SY5Y) are seeded in 6-well plates and treated with SH-42 at concentrations ranging from 0.01 to 10 uM for 48-72 hours. After treatment, cells are harvested and lipids are extracted using chloroform/methanol (2:1, v/v) following the Folch method. The organic phase is collected, dried under nitrogen, and resuspended in isopropanol. Sterol species (desmosterol, cholesterol, lathosterol) are separated and quantified by LC-MS/MS using a C18 column and multiple reaction monitoring (MRM) mode. For viability assessment, parallel cells are treated with SH-42 and assayed using the CellTiter-Glo luminescence assay after 72 hours. Changes in gene expression related to sterol synthesis can be analyzed by qPCR for SREBP target genes.
|
| Animal Protocol |
In vivo studies are typically conducted in male C57BL/6 mice (8-10 weeks old). SH-42 is formulated in a vehicle such as 5% DMSO + 95% saline or corn oil and administered via intraperitoneal injection (i.p.) at doses of 10, 30, and 100 mg/kg, once daily for 7-14 days. Control animals receive vehicle only. Blood samples are collected at baseline and at days 3, 7, and 14 via retro-orbital or tail vein puncture. Plasma is separated by centrifugation, and sterol levels (desmosterol and cholesterol) are quantified by LC-MS/MS. For tissue distribution, liver, brain, and adipose tissue are collected at necropsy, homogenized, and extracted for sterol analysis. Body weight and food intake are monitored daily. At study termination, tissues are also processed for histological examination to assess potential toxicity. An oral glucose tolerance test (OGTT) can be performed to assess metabolic effects. Pharmacokinetic studies involve blood collection at 0, 0.5, 1, 2, 4, 8, and 24 hours post-dose.
|
| ADME/Pharmacokinetics |
Pharmacokinetic data for SH-42 have not been fully characterized in the public domain. Based on its molecular weight (402.6 g/mol) and lipophilic nature (estimated logP ~5), the compound is expected to have high plasma protein binding (>95%), slow clearance, and a long terminal half-life (potentially >12 hours in rodents). After intraperitoneal administration, absorption may be moderate to good, with Tmax around 1-2 hours. Tissue distribution is likely extensive, with accumulation in lipid-rich tissues such as liver and adipose tissue. Brain penetration may occur but is unknown. For accurate PK analysis, an LC-MS/MS method would need to be developed for SH-42 quantification in plasma and tissues. The compound is soluble in chloroform and DMSO, but poorly soluble in aqueous buffers. For in vivo administration, formulation with PEG400 or cyclodextrins may be required. Stability studies should be conducted to assess degradation under storage conditions (powder at -20degC, protected from light).
|
| Toxicity/Toxicokinetics |
Detailed toxicology data for SH-42 are not publicly available, as the compound is a research tool. However, inhibition of DHCR24 is generally considered safe based on the fact that desmosterol accumulation is well-tolerated in various species and that DHCR24 knockout mice are viable. Potential toxicity may arise from cholesterol depletion in certain cell types, particularly in rapidly dividing cells or in the nervous system where desmosterol accumulates. In cell viability assays, SH-42 shows minimal cytotoxicity at concentrations up to 10 uM in several cell lines (e.g., HepG2, HEK293). In animal studies, doses up to 30-50 mg/kg are likely well-tolerated, although formal acute and sub-chronic studies have not been reported. Standard safety evaluations would include a 28-day repeated dose toxicity study in rats with hematology, clinical chemistry, and histopathology assessments. Genotoxicity should be evaluated using the Ames test and in vitro micronucleus assay. No data regarding reproductive or developmental toxicity are available. As with all research chemicals, appropriate safety precautions (gloves, lab coat, eye protection) should be used when handling SH-42.
|
| References | |
| Additional Infomation |
SH-42 is a research compound intended solely for laboratory use and is not approved for human therapy. It is a valuable pharmacological tool for studying the biological roles of DHCR24, cholesterol metabolism, and desmosterol function. The compound is used in metabolic research, neuroscience, and cancer biology, given the emerging role of DHCR24 in neuroprotection and tumor growth. It is typically available with purity >98% and stored as a powder at -20degC. For in vitro studies, stock solutions are prepared in DMSO (e.g., 10 mM) and stored at -80degC. The compound is not listed in any clinical trial databases. Its selectivity for human DHCR24 makes it suitable for use with human cell lines, but cross-reactivity with rodent DHCR24 should be verified for in vivo studies in mice. SH-42 is part of a growing class of small molecules targeting cholesterol biosynthesis pathways, which are being explored for the treatment of neurological diseases (e.g., Alzheimer's disease) and metabolic disorders.
|
| Molecular Formula |
C25H38O4
|
|---|---|
| Molecular Weight |
402.566828250885
|
| Exact Mass |
402.277
|
| CAS # |
2143952-36-5
|
| PubChem CID |
145952750
|
| Appearance |
White to off-white solid powder
|
| LogP |
5.8
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
29
|
| Complexity |
684
|
| Defined Atom Stereocenter Count |
8
|
| SMILES |
C[C@]12CC[C@@H](C[C@]1([H])CC=C1[C@]3([H])CC[C@@]([H])([C@]3(CC[C@@]12[H])C)[C@H](C)COC=O)OC(=O)C
|
| InChi Key |
ZMSGAXSBKXUQKY-PUCUFLQQSA-N
|
| InChi Code |
InChI=1S/C25H38O4/c1-16(14-28-15-26)21-7-8-22-20-6-5-18-13-19(29-17(2)27)9-11-24(18,3)23(20)10-12-25(21,22)4/h6,15-16,18-19,21-23H,5,7-14H2,1-4H3/t16-,18+,19+,21-,22+,23+,24+,25-/m1/s1
|
| Chemical Name |
[(3S,5S,9R,10S,13R,14R,17R)-17-[(2S)-1-formyloxypropan-2-yl]-10,13-dimethyl-2,3,4,5,6,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl] acetate
|
| 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 |
| 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 : ~2 mg/mL (~4.97 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (12.42 mM) in 6.6% Cremophor solution (1:1 Ethanol and Cremophor EL) 93.4% PBS (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication (<60°C).
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4840 mL | 12.4202 mL | 24.8404 mL | |
| 5 mM | 0.4968 mL | 2.4840 mL | 4.9681 mL | |
| 10 mM | 0.2484 mL | 1.2420 mL | 2.4840 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
