516-72-3

Usage

Uses

Used in Pharmaceutical Industry:
20ALPHA-HYDROXYCHOLESTEROL is used as a cytotoxic agent for its cholesterol oxidation product properties, which can have potential applications in the development of drugs targeting specific cellular pathways.
Used in Research Applications:
20ALPHA-HYDROXYCHOLESTEROL is used as a research tool for studying the hedgehog (Hh) signaling pathway, Smo receptor activation, and its role in various cellular processes, including osteogenic differentiation of pluripotent bone marrow stromal cells.
Used in Drug Development:
20ALPHA-HYDROXYCHOLESTEROL is used as a lead compound in the development of drugs targeting the hedgehog signaling pathway, which is involved in various diseases, including cancer.
Used in Cell Biology:
20ALPHA-HYDROXYCHOLESTEROL is used as a reagent in cell biology experiments to investigate the effects of Hh signaling modulation on cell differentiation and proliferation.

References

1) Janowski?et al. (1996),?An oxysterol signaling pathway mediated by the nuclear receptor LXR7alpha; Nature,?383?728 2) Kha?et al. (2004),?Oxysterols regulate differentiation of mesenchymal stem cells: Pro-bone and Anti-fat: J. Bone Min. Res.,?19?830 3) Kim?et al. (2010),?Osteogenic oxysterol, 20(S)-hydroxycholesterol, induces notch target gene expression in bone marrow stromal cells; J. Bone Miner. Res.,?25?7823 4) Dwyer?et al. (2007),?Oxysterols are novel activators of the hedgehog signaling pathway in pluripotent mesenchymal cells; J. Biol. Chem.,?282?8959 5) Nedelcu?et al. (2013);?Oxysterol binding to the extracellular domain of Smoothened in Hedgehog signaling; Nat. Chem. Biol.,?9?557 6) Cheng?et al. (2021);?A proteome-wide map of 20(S)-hydroxycholesterol interactors in cell membranes; Nat. Chem. Biol.,?17?1271

InChI:InChI=1/C27H46O2/c1-18(2)7-6-14-27(5,29)24-11-10-22-21-9-8-19-17-20(28)12-15-25(19,3)23(21)13-16-26(22,24)4/h8,18,20-24,28-29H,6-7,9-17H2,1-5H3/t20-,21-,22-,23-,24-,25-,26-,27+/m0/s1

Upstream product

• 1778-02-5 Pregnenolone acetate 
• 7429-94-9 isohexylmagnesium bromide 
• 57-88-5 cholesterol 
• 626-88-0 1-bromo-5-methylpentane 
• 145-13-1 Pregnenolone 
• 604-32-0 cholesteryl benzoate 
• 26048-47-5 5α,6β-dibromocholestan-3β-yl benzoate 
• 7154-75-8 4-methylpentyne 
• 115910-64-0 (20R)-3β-(tert-butyldimethylsilyl)oxycholest-5-en-22-yn-20-ol 
• 58701-45-4 3β-t-butyldimethylsilyloxy-pregn-5-en-20-one 
• 108354-83-2 20-ξ-hydroxy-23-oxocholest-5-en-3β-yl p-bromobenzoate 
• 15387-47-0 3α,5-cyclo-5α-pregnan-6β-ol-20-one 
• 24336-13-8 6β,20α-Dihydroxy-3α,5-cyclo-5α-cholestan 

Downstream Products

• 24339-15-9 3,6-Dioxo-20α-hydroxy-5α-cholestan 
• 145-13-1 Pregnenolone 

Relevant academic research and scientific papers

Preparation of oxysterols by c–h oxidation of dibromocholestane with ru(Bpga) catalyst

Seven mono-and dihydroxycholesterols were prepared by direct C–H oxidation of the cholestane skeleton with a recently developed Ru(Bpga) catalyst (Ru(Bpga) = [RuCl (bpga) (PPh3 )] Cl; bpga = 2-(bis(pyridin-2-ylmethyl)amino)-N-(2,6-dimethylphenyl)acetamide)). Due to the high selectivity of the Ru(Bpga) complex for tertiary C–H, the reaction afforded a mixture of 25-, 20-, 17-, and 14-oxygenated cholesterols that could be easily separated by high-performance liquid chromatography. These results suggest that late-stage C–H oxidation could be a viable strategy for preparing candidate metabolites of biologically important molecules.

Structure-activity relationships of oxysterol-derived pharmacological chaperones for Niemann-Pick type C1 protein

Niemann-Pick disease type C is a fatal neurodegenerative disease, and its major cause is mutations in NPC1 gene. This gene encodes NPC1 protein, a late endosomal polytopic membrane protein required for intracellular cholesterol trafficking. One prevalent mutation (I1061T) has been shown to cause a folding defect, which results in failure of endosomal localization of the protein, leading to loss-of-function phenotype. We have previously demonstrated that several oxysterols and their derivatives act as pharmacological chaperones; binding of these compounds to NPC1I1061T mutant protein corrects the localization/maturation defect of the mutant protein. Here, we disclose detailed structure-activity relationships of oxysterol derivatives as pharmacological chaperones for NPC1I1061T mutant.

Glucal-conjugated sterols as novel vascular leakage blocker: Structure-activity relationship focusing on the C17-side chain

A series of glucal-conjugated sterols as novel vascular leakage blocker were identified through design, synthesis and biologically evaluation. In addition, the structure-activity relationship (SAR) of the glucal-conjugated sterols focusing on the C17-side chain was also established. The sterol analogs linked with the rigid C17-side chain side chains exhibited potent cell survival activities. In particular, analog 21l, which possesses a cyclopentyl oxime moiety, was shown to have excellent pharmacological effects on retinal vascular leakage in a diabetic mouse model.

NOVEL VASCULAR LEAK INHIBITOR

The present disclosure relates to a novel vascular leakage inhibitor. The novel vascular leakage inhibitor of the present disclosure inhibits the apoptosis of vascular endothelial cells, inhibits the formation of actin stress fibers induced by VEGF, enhances the cortical actin ring structure, and improves the stability of the tight junctions (TJs) between vascular cells, thereby inhibiting vascular leakage. The vascular leakage inhibitor of the present disclosure has the activity of not only reducing vascular permeability but also recovering the integrity of damaged blood vessels. Accordingly, the vascular leakage inhibitor of the present disclosure can prevent or treat various diseases caused by vascular leakage. Since the vascular leakage inhibitor of the present disclosure is synthesized from commercially available or easily synthesizable cholesterols, it has remarkably superior feasibility of commercial synthesis.

Novel oxysterols activate the Hedgehog pathway and induce osteogenesis

Localized induction of bone formation is essential during orthopedic procedures that involve skeletal repair, such as surgical treatment of non-union bone fractures and degenerative disk disease. Herein we disclose the synthesis and biological evaluation of novel oxysterol derivatives designed as anabolic bone growth agents. Structure-activity relationship studies of oxysterol 4 have identified analogues such as 18, 21 and 30. These new analogues are characterized by higher potency in an osteoblast differentiation assay and/or by increased metabolic stability in human liver microsomes. Oxysterols 4, 18 and 21 were evaluated in vivo in a rat spinal fusion model.

INHIBITION OF PPAR GAMMA EXPRESSION IN PREADIPOCYTE CELLS BY OXYSTEROLS

This invention relates, e.g., to methods and agents to inhibit peroxisome proliferator activated receptor expression (PPAR) in preadipocytes.

Stereoselective synthesis of petrosterol and a formal synthesis of aragusterols

Stereoselective construction of a steroidal side chain containing a 26-27 cyclopropane ring, compound 22, has been achieved by an intramolecular cyclisation of the corresponding β-methylsulfonyloxy cyanide 16, derived from a chiral cyclopentane derivative. Compound 22 has been further utilised in the synthesis of the naturally occurring steroid petrosterol 3.