Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMHL48F)

• Drug Name: ARACHIDONYL TRIFLUOROMETHYLKETONE Drug Info
• Synonyms: Arachidonyl trifluoromethyl ketone; Aacocf3; arachidonyl trifluoromethyl ketone; Arachidonyltrifluoromethane; 149301-79-1; Arachidonic acid trifluoromethyl ketone; Arachidonyltrifluoromethyl Ketone; ATFMK; UNII-00XIW1CR0F; C21H31F3O; (6Z,9Z,12Z,15Z)-1,1,1-trifluorohenicosa-6,9,12,15-tetraen-2-one; 00XIW1CR0F; CHEBI:2341; CHEMBL281211; 1,1,1-Trifluoro-6Z,9Z,12Z,15Z-heneicosatetraen-2-one; 6,9,12,15-Heneicosatetraen-2-one, 1,1,1-trifluoro-, (6Z,9Z,12Z,15Z)-; 6,9,12,15-Heneicosatetraen-2-one, 1,1,1-trifluoro-, (all-Z)-; Arachidonyl trifluoromethylketone; Arachidonyltrifluoromethyl ketone

Indication

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

• Cross-matching ID:
  PubChem CID: 5280436
  ChEBI ID: CHEBI:2341
  CAS Number: CAS 149301-79-1
  TTD Drug ID: DMHL48F

Molecule-Related Drug Atlas

Drug(s) Targeting Fatty acid amide hydrolase (FAAH)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[5]
Thiopental	DMGP8AX	Anaesthesia	9A78.6	Approved	[6]
JNJ-42165279	DM72GZO	Anxiety disorder	6B00-6B0Z	Phase 2	[7]
SSR411298	DMGTB2Q	Major depressive disorder	6A70.3	Phase 2	[8]
IW-6118	DMP42W1	Inflammation	1A00-CA43.1	Phase 2	[9]
PF-04457845	DMPRYU1	Liver disease	DB90-BD99	Phase 2	[10]
IPI-940	DMEIM5G	Pain	MG30-MG3Z	Phase 1	[11]
PMID29053063-Compound-11d	DMDRK68	N. A.	N. A.	Patented	[12]
Piperazine carbamic compound 1	DMZSYU4	N. A.	N. A.	Patented	[12]
Piperazine carbamic compound 2	DMMQ0ZO	N. A.	N. A.	Patented	[12]

Drug(s) Targeting Cytosolic phospholipase A2 (GIVA cPLA2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ZPL521	DMPZE2G	Atopic dermatitis	EA80	Phase 1/2	[13]
EFIPLADIB	DMJ0A5U	Asthma	CA23	Terminated	[14]
1,1,1-Trifluoro-7-phenylheptan-2-one	DMLHVWP	Discovery agent	N.A.	Investigative	[15]
1,1,1-Trifluoro-8-phenyl-octan-2-one	DMYENI7	Discovery agent	N.A.	Investigative	[15]
AR-C70484XX	DMU3A57	Discovery agent	N.A.	Investigative	[3]
1-Imidazol-1-yl-3-(4-octylphenoxy)propan-2-one	DM3JHVL	Discovery agent	N.A.	Investigative	[3]
AX-006	DMDWCY7	Discovery agent	N.A.	Investigative	[16]
N-(4-Ethoxybutyl)-2-oxohexadecanamide	DM012TN	Discovery agent	N.A.	Investigative	[17]
[3,4''']biflavone	DMHU4NS	Discovery agent	N.A.	Investigative	[18]
1,1,1-Trifluoro-6-(naphthalen-2-yl)hexan-2-one	DMZ2VE3	Discovery agent	N.A.	Investigative	[19]

Drug(s) Affected By Insulin (INS)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tolbutamide	DM02AWV	Advanced cancer	2A00-2F9Z	Approved	[20]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[21]
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[22]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[23]
Fructose	DM43AN2	Vomiting	MD90	Approved	[24]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[25]
Glimepiride	DM5FSJA	Diabetic complication	5A2Y	Approved	[26]
Clonidine	DM6RZ9Q	Attention deficit hyperactivity disorder	6A05.Z	Approved	[27]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[28]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[29]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cytosolic phospholipase A2 (GIVA cPLA2)	TTT1JVS	PA24A_HUMAN	Inhibitor	[2]
Fatty acid amide hydrolase (FAAH)	TTDP1UC	NOUNIPROTAC	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Insulin (INS)	OTZ85PDU	INS_HUMAN	Protein Interaction/Cellular Processes	[4]

References

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• [2] 85-kDa cPLA(2) plays a critical role in PPAR-mediated gene transcription in human hepatoma cells. Am J Physiol Gastrointest Liver Physiol. 2002 Apr;282(4):G586-97.
• [3] 1-Indol-1-yl-propan-2-ones and related heterocyclic compounds as dual inhibitors of cytosolic phospholipase A(2)alpha and fatty acid amide hydrolase. Bioorg Med Chem. 2010 Jan 15;18(2):945-52.
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• [6] The general anesthetic propofol increases brain N-arachidonylethanolamine (anandamide) content and inhibits fatty acid amide hydrolase. Br J Pharmacol. 2003 Jul;139(5):1005-13.
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• [8] Pharma & Vaccines. Product Development Pipeline. April 29 2009.
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• [10] Discovery of PF-04457845: A Highly Potent, Orally Bioavailable, and Selective Urea FAAH Inhibitor. ACS Med Chem Lett. 2011 Feb 10;2(2):91-96.
• [11] 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. (Target id: 1400).
• [12] A patent review of Monoacylglycerol Lipase (MAGL) inhibitors (2013-2017).Expert Opin Ther Pat. 2017 Dec;27(12):1341-1351.
• [13] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [14] Reactions of functionalized sulfonamides: application to lowering the lipophilicity of cytosolic phospholipase A2alpha inhibitors. J Med Chem. 2009 Feb 26;52(4):1156-71.
• [15] Synthesis of polyfluoro ketones for selective inhibition of human phospholipase A2 enzymes. J Med Chem. 2008 Dec 25;51(24):8027-37.
• [16] 2-Oxoamide inhibitors of phospholipase A2 activity and cellular arachidonate release based on dipeptides and pseudodipeptides. Bioorg Med Chem. 2009 Jul 1;17(13):4833-43.
• [17] Structure-activity relationships of natural and non-natural amino acid-based amide and 2-oxoamide inhibitors of human phospholipase A(2) enzymes. Bioorg Med Chem. 2008 Dec 15;16(24):10257-69.
• [18] Inhibitory effect of synthetic C-C biflavones on various phospholipase A(2)s activity. Bioorg Med Chem. 2007 Nov 15;15(22):7138-43.
• [19] Potent and selective fluoroketone inhibitors of group VIA calcium-independent phospholipase A2. J Med Chem. 2010 May 13;53(9):3602-10.
• [20] Amino acid polymorphisms in the ATP-regulatable inward rectifier Kir6.2 and their relationships to glucose- and tolbutamide-induced insulin secretion, the insulin sensitivity index, and NIDDM. Diabetes. 1997 Mar;46(3):508-12. doi: 10.2337/diab.46.3.508.
• [21] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [22] A receptor mechanism for the inhibition of insulin release by epinephrine in man. J Clin Invest. 1967 Jan;46(1):86-94. doi: 10.1172/JCI105514.
• [23] Vasodilatory effects of troglitazone improve blood pressure at rest and during mental stress in type 2 diabetes mellitus. Hypertension. 1999 Jul;34(1):83-8. doi: 10.1161/01.hyp.34.1.83.
• [24] Quinapril treatment restores the vasodilator action of insulin in fructose-hypertensive rats. Clin Exp Pharmacol Physiol. 2002 May-Jun;29(5-6):381-5. doi: 10.1046/j.1440-1681.2002.03668.x.
• [25] Retinoic acid can induce markers of endocrine transdifferentiation in pancreatic ductal adenocarcinoma: preliminary observations from an in vitro cell line model. J Clin Pathol. 2006 Jun;59(6):603-10. doi: 10.1136/jcp.2005.032003. Epub 2006 Feb 10.
• [26] Effects of prolonged in vitro exposure to sulphonylureas on the function and survival of human islets. J Diabetes Complications. 2005 Jan-Feb;19(1):60-4. doi: 10.1016/j.jdiacomp.2004.05.001.
• [27] Clonidine effect on insulin secretion and lipolysis in man. Acta Diabetol Lat. 1978 May-Aug;15(3-4):192-7. doi: 10.1007/BF02581064.
• [28] Beta-adrenergic contribution to glucagon-induced glucose production and insulin secretion in uremia. Am J Physiol. 1986 Sep;251(3 Pt 1):E322-7. doi: 10.1152/ajpendo.1986.251.3.E322.
• [29] Effect of testosterone replacement on whole body glucose utilisation and other cardiovascular risk factors in males with idiopathic hypogonadotrophic hypogonadism. Horm Metab Res. 1998 Oct;30(10):642-5. doi: 10.1055/s-2007-978950.