Details of the Drug

General Information of Drug (ID: DMB4A8I)

• Drug Name: MANOALIDE
• Synonyms: manoalide; UNII-E1DK0157K9; 75088-80-1; CHEMBL463914; CHEBI:66666; E1DK0157K9; 2(5H)-Furanone, 4-(3,6-dihydro-6-hydroxy-5-(4-methyl-6-(2,6,6-trimethyl-1-cyclohexen-1-yl)-3-hexenyl)-2H-pyran-2-yl)-5-hydroxy-; 2(5H)-Furanone, 4-((2R,6R)-3,6-dihydro-6-hydroxy-5-((3E)-4-methyl-6-(2,6,6-trimethyl-1-cyclohexen-1-yl)-3-hexenyl)-2H-pyran-2-yl)-5-hydroxy-, (5R)-; AC1O5NJS; SCHEMBL20551728; MolPort-020-000-975

Indication

Disease Entry	ICD 11	Status	REF
Arthritis	FA20	Phase 2	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 416.5
  Topological Polar Surface Area (xlogp); 3.5
  Rotatable Bond Count (rotbonds); 7
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 5
• Chemical Identifiers:
  Formula: C25H36O5
  IUPAC Name: (2R)-2-hydroxy-3-[(2R,6R)-6-hydroxy-5-[(E)-4-methyl-6-(2,6,6-trimethylcyclohexen-1-yl)hex-3-enyl]-3,6-dihydro-2H-pyran-2-yl]-2H-furan-5-one
  Canonical SMILES: CC1=C(C(CCC1)(C)C)CC/C(=C/CCC2=CC[C@@H](O[C@H]2O)C3=CC(=O)O[C@H]3O)/C
  InChI: InChI=1S/C25H36O5/c1-16(10-12-20-17(2)8-6-14-25(20,3)4)7-5-9-18-11-13-21(29-23(18)27)19-15-22(26)30-24(19)28/h7,11,15,21,23-24,27-28H,5-6,8-10,12-14H2,1-4H3/b16-7+/t21-,23-,24-/m1/s1
  InChIKey: FGJIDQWRRLDGDB-CPIXEKRISA-N
• Cross-matching ID:
  PubChem CID: 6437368
  ChEBI ID: CHEBI:66666
  CAS Number: 75088-80-1
  TTD ID: D00XQO

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Phospholipase A2 (PLA2G1B)	TT9V5JH	PA21B_HUMAN	Modulator	[2], [3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Arthritis
• ICD Disease Classification: FA20

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Phospholipase A2 (PLA2G1B)	DTT	PLA2G1B	2.65E-01	-0.08	-0.21

References

• [1] In situ aquaculture methods for Dysidea avara (Demospongiae, Porifera) in the northwestern Mediterranean. Mar Drugs. 2010 May 26;8(6):1731-42.
• [2] Manoalide, a phospholipase A2 inhibitor, inhibits arachidonate incorporation and turnover in brain phospholipids of the awake rat. Neurochem Res. 1998 Oct;23(10):1251-7.
• [3] The effects of the phospholipase A2 inhibitor, manoalide, on cartilage degradation, stromelysin expression, and synovial fluid cell count induced b... Arthritis Rheum. 1996 Aug;39(8):1292-9.
• [4] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [5] Novel antifungal agents, targets or therapeutic strategies for the treatment of invasive fungal diseases: a review of the literature (2005-2009). Rev Iberoam Micol. 2009 Mar 31;26(1):15-22.
• [6] Clocortolone pivalate: a paired comparison clinical trial of a new topical steroid in eczema/atopic dermatitis. Cutis. 1980 Jan;25(1):96-8.
• [7] Utilization of epidermal phospholipase A2 inhibition to monitor topical steroid action. Br J Dermatol. 1984 Jul;111 Suppl 27:195-203.
• [8] Structures from powders: diflorasone diacetate. Steroids. 2009 Jan;74(1):102-11.
• [9] Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell anergy in patients allergic to bee venom. J Allergy Clin Immunol. 1998 Jun;101(6 Pt 1):747-54.
• [10] Synthesis of benzoyl phenyl benzoates as effective inhibitors for phospholipase A2 and hyaluronidase enzymes. Bioorg Med Chem Lett. 2005 Sep 15;15(18):4100-4.
• [11] Phospholipase A2, group IVA (cytosolic, calcium-dependent) (PLA2G4A). SciBX 1(41); doi:10.1038/scibx.2008.999. Nov. 13 2008
• [12] A novel treatment of contact dermatitis by topical application of phospholipase A2 inhibitor: a double-blind placebo-controlled pilot study. Int J Immunopathol Pharmacol. 2007 Jan-Mar;20(1):191-5.
• [13] Effect of treatment for 12 weeks with rilapladib, a lipoprotein-associated phospholipase A2 inhibitor, on arterial inflammation as assessed with 18F-fluorodeoxyglucose-positron emission tomography imaging.J Am Coll Cardiol.2014 Jan 7-14;63(1):86-8.