Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS6LX01)

• DOT Name: Fatty-acid amide hydrolase 2 (FAAH2)
• Synonyms: EC 3.5.1.99; Amidase domain-containing protein; Anandamide amidohydrolase 2; Oleamide hydrolase 2
• Gene Name: FAAH2
• UniProt ID: FAAH2_HUMAN
• EC Number: 3.5.1.99
• Pfam ID: PF01425
• Sequence:
  MAPSFTARIQLFLLRALGFLIGLVGRAALVLGGPKFASKTPRPVTEPLLLLSGMQLAKLI
  RQRKVKCIDVVQAYINRIKDVNPMINGIVKYRFEEAMKEAHAVDQKLAEKQEDEATLENK
  WPFLGVPLTVKEAFQLQGMPNSSGLMNRRDAIAKTDATVVALLKGAGAIPLGITNCSELC
  MWYESSNKIYGRSNNPYDLQHIVGGSSGGEGCTLAAACSVIGVGSDIGGSIRMPAFFNGI
  FGHKPSPGVVPNKGQFPLAVGAQELFLCTGPMCRYAEDLAPMLKVMAGPGIKRLKLDTKV
  HLKDLKFYWMEHDGGSFLMSKVDQDLIMTQKKVVVHLETILGASVQHVKLKKMKYSFQLW
  IAMMSAKGHDGKEPVKFVDLLGDHGKHVSPLWELIKWCLGLSVYTIPSIGLALLEEKLRY
  SNEKYQKFKAVEESLRKELVDMLGDDGVFLYPSHPTVAPKHHVPLTRPFNFAYTGVFSAL
  GLPVTQCPLGLNAKGLPLGIQVVAGPFNDHLTLAVAQYLEKTFGGWVCPGKF
• Function: Catalyzes the hydrolysis of endogenous amidated lipids like the sleep-inducing lipid oleamide ((9Z)-octadecenamide), the endocannabinoid anandamide (N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine), as well as other fatty amides, to their corresponding fatty acids, thereby regulating the signaling functions of these molecules. Hydrolyzes monounsaturated substrate anandamide preferentially as compared to polyunsaturated substrates.
• Tissue Specificity: Expressed in kidney, liver, lung, prostate, heart and ovary.
• Reactome Pathway: Arachidonic acid metabolism (R-HSA-2142753)
• BioCyc Pathway: MetaCyc:HS09254-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Fatty-acid amide hydrolase 2 (FAAH2).	[1]
ASP-8477	DMBZQS7	Phase 2	ASP-8477 decreases the activity of Fatty-acid amide hydrolase 2 (FAAH2).	[3]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Fatty-acid amide hydrolase 2 (FAAH2).	[5]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Fatty-acid amide hydrolase 2 (FAAH2).	[6]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Fatty-acid amide hydrolase 2 (FAAH2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Fatty-acid amide hydrolase 2 (FAAH2).	[4]

References

• [1] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [2] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [3] In vitro and in vivo pharmacological characterization of ASP8477: A novel highly selective fatty acid amide hydrolase inhibitor. Eur J Pharmacol. 2017 Nov 15;815:42-48. doi: 10.1016/j.ejphar.2017.10.007. Epub 2017 Oct 7.
• [4] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [5] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [6] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.