Details of the Drug

General Information of Drug (ID: DMV8SUM)

• Drug Name: desmosterol
• Synonyms: DESMOSTEROL; 24-Dehydrocholesterol; 313-04-2; UNII-ANP93865R8; cholest-5,24-dien-3beta-ol; Cholesta-5,24-dien-3beta-ol; NSC 226126; CHEBI:17737; 3beta-cholesta-5,24-dien-3-ol; ANP93865R8; (3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylhept-5-en-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol; Cholesta-5,24-dien-3-ol; desmesterol; EINECS 206-236-2; 24-dehydro Cholesterol; 24,25-Dehydrocholesterol; AC1L97ME; Cholesta-5,24-dien-3b-ol; 5,24-Cholestadien-3beta-ol; 5,24-Cholestadien-3

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 384.6
  Logarithm of the Partition Coefficient (xlogp); 8.3
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 1
• Chemical Identifiers:
  Formula: C27H44O
  IUPAC Name: (3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylhept-5-en-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol
  Canonical SMILES: C[C@H](CCC=C(C)C)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CC=C4[C@@]3(CC[C@@H](C4)O)C)C
  InChI: InChI=1S/C27H44O/c1-18(2)7-6-8-19(3)23-11-12-24-22-10-9-20-17-21(28)13-15-26(20,4)25(22)14-16-27(23,24)5/h7,9,19,21-25,28H,6,8,10-17H2,1-5H3/t19-,21+,22+,23-,24+,25+,26+,27-/m1/s1
  InChIKey: AVSXSVCZWQODGV-DPAQBDIFSA-N
• Cross-matching ID:
  PubChem CID: 439577
  ChEBI ID: CHEMBL455876
  CAS Number: 313-04-2
  TTD ID: D01RNA
  INTEDE ID: DR0437
• Drug-Molecule Activity Atlas (DMA)NEW: Click to Jump to the Detailed DMA Information of This Drug
• Drug ADMET Endpoint Profile (DAE)NEW: Click to Jump to the Detailed DAE Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Farnesoid X-activated receptor (FXR)	TTS4UGC	NR1H4_HUMAN	Agonist	[2]
Oxysterols receptor LXR-alpha (NR1H3)	TTECBXN	NR1H3_HUMAN	Agonist	[3]
Oxysterols receptor LXR-beta (NR1H2)	TTXA6PH	NR1H2_HUMAN	Agonist	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Delta(24)-sterol reductase (DHCR24)	DEAXY04	DHC24_HUMAN	Substrate	[4]
Sterol Delta(7)-reductase (DHCR7)	DEL7GFA	DHCR7_HUMAN	Substrate	[5]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
C-type lectin domain family 4 member E (CLEC4E)	OT7P8ICY	CLC4E_HUMAN	Gene/Protein Processing	[6]
E3 ubiquitin-protein ligase MARCHF6 (MARCHF6)	OTBTA03N	MARH6_HUMAN	Protein Interaction/Cellular Processes	[7]
Sterol 26-hydroxylase, mitochondrial (CYP27A1)	OT649C01	CP27A_HUMAN	Regulation of Drug Effects	[8]

Molecular Expression Atlas of This Drug

• The Studied Disease: Discovery agent
• ICD Disease Classification: N.A.

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Farnesoid X-activated receptor (FXR)	DTT	NR1H4	5.72E-01	0.39	1.68
Sterol Delta(7)-reductase (DHCR7)	DME	DHCR7	1.14E-01	2.27E-01	6.36E-01
Delta(24)-sterol reductase (DHCR24)	DME	DHCR24	9.64E-01	-1.44E-01	-5.66E-01

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2748).
• [2] Identification of farnesoid X receptor beta as a novel mammalian nuclear receptor sensing lanosterol. Mol Cell Biol. 2003 Feb;23(3):864-72.
• [3] Sterol intermediates from cholesterol biosynthetic pathway as liver X receptor ligands. J Biol Chem. 2006 Sep 22;281(38):27816-26.
• [4] Alzheimer's disease: brain desmosterol levels. J Alzheimers Dis. 2013;33(3):881-8.
• [5] Inhibitors of 7-dehydrocholesterol reductase: screening of a collection of pharmacologically active compounds in Neuro2a cells. Chem Res Toxicol. 2016 May 16;29(5):892-900.
• [6] Human Mincle Binds to Cholesterol Crystals and Triggers Innate Immune Responses. J Biol Chem. 2015 Oct 16;290(42):25322-32. doi: 10.1074/jbc.M115.645234. Epub 2015 Aug 20.
• [7] Cholesterol increases protein levels of the E3 ligase MARCH6 and thereby stimulates protein degradation. J Biol Chem. 2019 Feb 15;294(7):2436-2448. doi: 10.1074/jbc.RA118.005069. Epub 2018 Dec 13.
• [8] Novel sterols synthesized via the CYP27A1 metabolic pathway. Arch Biochem Biophys. 2003 Dec 1;420(1):35-9. doi: 10.1016/j.abb.2003.09.028.