Details of the Drug

General Information of Drug (ID: DM2L3PE)

• Drug Name: Hyperforin
• Synonyms: hyperforin; 11079-53-1; hyperforine; hiperforina; UNII-RM741E34FP; CHEBI:5834; RM741E34FP; CHEMBL1237210; (1R,5S,6R,7S)-4-hydroxy-6-methyl-1,3,7-tris(3-methylbut-2-en-1-yl)-6-(4-methylpent-3-en-1-yl)-5-(2-methylpropanoyl)bicyclo[3.3.1]non-3-ene-2,9-dione; (1R,5S,6R,7S)-4-hydroxy-5-isobutyryl-6-methyl-1,3,7-tris(3-methylbut-2-en-1-yl)-6-(4-methylpent-3-en-1-yl)bicyclo[3.3.1]non-3-ene-2,9-dione; HSDB 7646; (+)-Hyperforin; Spectrum5_002025; SCHEMBL98723; CHEMBL501711; GTPL2764; SCHEMBL15557965; Hyperforin, &gt

Indication

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

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 3:
  Molecular Weight (mw); 536.8
  Logarithm of the Partition Coefficient (xlogp); 9.6
  Rotatable Bond Count (rotbonds); 11
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property: Half-life: The concentration or amount of drug in body reduced by one-half in 9 hours [2]
• Chemical Identifiers:
  Formula: C35H52O4
  IUPAC Name: (1R,5R,7S,8R)-4-hydroxy-8-methyl-3,5,7-tris(3-methylbut-2-enyl)-8-(4-methylpent-3-enyl)-1-(2-methylpropanoyl)bicyclo[3.3.1]non-3-ene-2,9-dione
  Canonical SMILES: CC(C)C(=O)[C@]12C(=O)C(=C([C@](C1=O)(C[C@@H]([C@@]2(C)CCC=C(C)C)CC=C(C)C)CC=C(C)C)O)CC=C(C)C
  InChI: InChI=1S/C35H52O4/c1-22(2)13-12-19-33(11)27(16-14-23(3)4)21-34(20-18-25(7)8)30(37)28(17-15-24(5)6)31(38)35(33,32(34)39)29(36)26(9)10/h13-15,18,26-27,37H,12,16-17,19-21H2,1-11H3/t27-,33+,34+,35-/m0/s1
  InChIKey: KGSZHKRKHXOAMG-HQKKAZOISA-N
• Cross-matching ID:
  PubChem CID: 441298
  ChEBI ID: CHEBI:5834
  CAS Number: 11079-53-1
  DrugBank ID: DB01892
  TTD ID: D09VTJ
  VARIDT ID: DR00582

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Arachidonate 5-lipoxygenase (5-LOX)	TT2J34L	LOX5_HUMAN	Inhibitor	[3]
Pregnane X receptor (NR1I2)	TT7LCTF	NR1I2_HUMAN	Binder	[4]
Prostaglandin G/H synthase 1 (COX-1)	TT8NGED	PGH1_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1)	OTG2T749	CP24A_HUMAN	Gene/Protein Processing	[5]
5-aminolevulinate synthase, non-specific, mitochondrial (ALAS1)	OTQY6ZSF	HEM1_HUMAN	Gene/Protein Processing	[6]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Gene/Protein Processing	[7]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Gene/Protein Processing	[8]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Gene/Protein Processing	[6]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Gene/Protein Processing	[7]
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Gene/Protein Processing	[7]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Protein Interaction/Cellular Processes	[7]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Protein Interaction/Cellular Processes	[7]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Gene/Protein Processing	[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
Prostaglandin G/H synthase 1 (COX-1)	DTT	PTGS1	3.97E-03	0.16	0.43

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: 2764).
• [2] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [3] Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase. Biochem Pharmacol. 2002 Dec 15;64(12):1767-75.
• [4] Pregnane X receptor (PXR) regulates P-glycoprotein at the blood-brain barrier: functional similarities between pig and human PXR. J Pharmacol Exp Ther. 2009 Apr;329(1):141-9.
• [5] Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia. J Clin Invest. 2005 Jan;115(1):177-86.
• [6] No activation of human pregnane X receptor by hyperforin-related phloroglucinols. J Pharmacol Exp Ther. 2014 Mar;348(3):393-400.
• [7] Hyperforin induces apoptosis through extrinsic/intrinsic pathways and inhibits EGFR/ERK/NF-B-mediated anti-apoptotic potential in glioblastoma. Environ Toxicol. 2020 Oct;35(10):1058-1069. doi: 10.1002/tox.22942. Epub 2020 Jun 2.
• [8] Neuroprotective role of hyperforin on aluminum maltolate-induced oxidative damage and apoptosis in PC12 cells and SH-SY5Y cells. Chem Biol Interact. 2019 Feb 1;299:15-26. doi: 10.1016/j.cbi.2018.11.016. Epub 2018 Nov 24.