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Chemical Structure| 516-72-3 Chemical Structure| 516-72-3

Structure of 20(S)-Hydroxycholesterol
CAS No.: 516-72-3

Chemical Structure| 516-72-3

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20(S)-Hydroxycholesterol is an allosteric activator of the Hedgehog signaling pathway Smoothened (Smo) oncoprotein. It activates Hedgehog (Hh) signaling with EC50 value of ~ 3μM for induction of Hh reporter gene transcription in NIH 3T3 cells.

Synonyms: 20α-Hydroxycholesterol

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Product Citations

Product Citations

Xiao, Xu ; Kim, Youngjae ; Romartinez-Alonso, Beatriz ; Sirvydis, Kristupas ; Ory, Daniel S. ; Schwabe, John W. R. , et al.

Abstract: The Aster proteins (encoded by the Gramd1a-c genes) contain a ligand-binding fold structurally similar to a START domain and mediate nonvesicular plasma membrane (PM) to endoplasmic reticulum (ER) cholesterol transport. In an effort to develop small mol. modulators of Asters, we identified 20α-hydroxycholesterol (HC) and U18666A as lead compounds Unfortunately, both 20α-HC and U18666A target other sterol homeostatic proteins, limiting their utility. 20α-HC inhibits sterol regulatory element-binding protein 2 (SREBP2) processing, and U18666A is an inhibitor of the vesicular trafficking protein Niemann-Pick C1 (NPC1). To develop potent and selective Aster inhibitors, we synthesized a series of compounds by modifying 20α-HC and U18666A. Among these, AI (Aster inhibitor)-1l, which has a longer side chain than 20α-HC, selectively bound to Aster-C. The crystal structure of Aster-C in complex with AI-1l suggests that sequence and flexibility differences in the loop that gates the binding cavity may account for the ligand specificity for Aster C. We further identified the U18666A analog AI-3d as a potent inhibitor of all three Aster proteins. AI-3d blocks the ability of Asters to bind and transfer cholesterol in vitro and in cells. Importantly, AI-3d also inhibits the movement of low-d. lipoprotein (LDL) cholesterol to the ER, although AI-3d does not block NPC1. This finding positions the nonvesicular Aster pathway downstream of NPC1-dependent vesicular transport in the movement of LDL cholesterol to the ER. Selective Aster inhibitors represent useful chem. tools to distinguish vesicular and nonvesicular sterol transport mechanisms in mammalian cells.

Keywords: cholesterol ; lipid metabolism ; lipid transport

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Product Details of 20(S)-Hydroxycholesterol

CAS No. :516-72-3
Formula : C27H46O2
M.W : 402.65
SMILES Code : CC(C)CCC[C@@](C)(O)[C@H]1CC[C@@]2([H])[C@]3([H])CC=C4CC(O)CC[C@]4(C)[C@@]3([H])CC[C@]12C
Synonyms :
20α-Hydroxycholesterol
MDL No. :MFCD16661190
InChI Key :MCKLJFJEQRYRQT-APGJSSKUSA-N
Pubchem ID :121935

Safety of 20(S)-Hydroxycholesterol

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

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Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.48mL

0.50mL

0.25mL

12.42mL

2.48mL

1.24mL

24.84mL

4.97mL

2.48mL

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