Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTDMBF5)

• DTT Name: Arachidonate 5-lipoxygenase activating protein (FLAP)
• Synonyms: MK-886-binding protein; FLAP; ALOX5AP
• Gene Name: ALOX5AP
• DTT Type: Discontinued target; [1]
• Related Disease:
  Asthma [ICD-11: CA23]
  Cardiovascular disease [ICD-11: BA00-BE2Z]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]
  Allergic/hypersensitivity disorder [ICD-11: 4A80-4A8Z]
• UniProt ID: AL5AP_HUMAN
• TTD ID: T46642
• Sequence:
  MDQETVGNVVLLAIVTLISVVQNGFFAHKVEHESRTQNGRSFQRTGTLAFERVYTANQNC
  VDAYPTFLAVLWSAGLLCSQVPAAFAGLMYLFVRQKYFVGYLGERTQSTPGYIFGKRIIL
  FLFLMSVAGIFNYYLIFFFGSDFENYIKTISTTISPLLLIP
• Function: Required for leukotrienebiosynthesis by ALOX5 (5- lipoxygenase). Anchors ALOX5 to the membrane. Binds arachidonic acid, and could play an essential role in the transfer of arachidonic acid to ALOX5. Binds to MK-886, a compound that blocks the biosynthesis of leukotrienes.
• Reactome Pathway:
  Synthesis of Leukotrienes (LT) and Eoxins (EX) (R-HSA-2142691)
  Synthesis of Lipoxins (LX) (R-HSA-2142700)
  Synthesis of 5-eicosatetraenoic acids (R-HSA-2142688)
• BioCyc Pathway: MetaCyc:ENSG00000132965-MON

Molecular Interaction Atlas (MIA) of This DTT

6 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DG031	DMO3AJS	Asthma	CA23	Discontinued in Phase 3	[1], [2]
AM103	DMAQNBW	Cardiovascular disease	BA00-BE2Z	Discontinued in Phase 2	[3]
GSK2190914	DMHZQ0T	Asthma	CA23	Discontinued in Phase 2	[4]
GSK2190915	DM89AV2	Asthma	CA23	Discontinued in Phase 2	[5]
AZD4769	DMA3OWI	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[6]
A-93178	DM1KBAY	Allergy	4A80-4A85	Terminated	[7]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-671,480	DMP4QCJ	Discovery agent	N.A.	Investigative	[8]
L-689,037	DMCH3ZK	Discovery agent	N.A.	Investigative	[6]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Asthma	CA23	Nasal and bronchial airway	9.89E-01	-0.06	-0.05

References

• [1] BAY x 1005 attenuates atherosclerosis in apoE/LDLR - double knockout mice. J Physiol Pharmacol. 2007 Sep;58(3):583-8.
• [2] Effects of a 5-lipoxygenase-activating protein inhibitor on biomarkers associated with risk of myocardial infarction: a randomized trial. JAMA. 2005 May 11;293(18):2245-56.
• [3] AM103 Experimental Treatment for Respiratory Diseases. Amira Pharmaceuticals/GSK. 2009.
• [4] FLAP inhibitors for the treatment of inflammatory diseases. Curr Opin Investig Drugs. 2009 Nov;10(11):1163-72.
• [5] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [6] 5-Lipoxygenase-activating protein is the target of a novel hybrid of two classes of leukotriene biosynthesis inhibitors. Mol Pharmacol. 1992 Feb;41(2):267-72.
• [7] Characterization of A-93178, an iminoxy-quinoline inhibitor of leukotriene biosynthesis. Adv Exp Med Biol. 1997;433:91-4.
• [8] 5-Lipoxygenase-activating protein is the target of a quinoline class of leukotriene synthesis inhibitors. Mol Pharmacol. 1991 Jul;40(1):22-7.