Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT0MI3F)

• DTT Name: 5-HT 1F receptor (HTR1F)
• Synonyms: Serotonin receptor 1F; HTR1EL; 5-hydroxytryptamine receptor 1F; 5-HT1F receptor; 5-HT1F; 5-HT-1F
• Gene Name: HTR1F
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: 5HT1F_HUMAN
• TTD ID: T78656
• Sequence:
  MDFLNSSDQNLTSEELLNRMPSKILVSLTLSGLALMTTTINSLVIAAIIVTRKLHHPANY
  LICSLAVTDFLVAVLVMPFSIVYIVRESWIMGQVVCDIWLSVDITCCTCSILHLSAIALD
  RYRAITDAVEYARKRTPKHAGIMITIVWIISVFISMPPLFWRHQGTSRDDECIIKHDHIV
  STIYSTFGAFYIPLALILILYYKIYRAAKTLYHKRQASRIAKEEVNGQVLLESGEKSTKS
  VSTSYVLEKSLSDPSTDFDKIHSTVRSLRSEFKHEKSWRRQKISGTRERKAATTLGLILG
  AFVICWLPFFVKELVVNVCDKCKISEEMSNFLAWLGYLNSLINPLIYTIFNEDFKKAFQK
  LVRCRC
• Function: Functions as a receptor for various alkaloids and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. G-protein coupled receptor for 5-hydroxytryptamine (serotonin).
• KEGG Pathway:
  cAMP signaling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Serotonergic synapse (hsa04726)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Serotonin receptors (R-HSA-390666)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lasmiditan	DMXLVDT	Migraine	8A80	Approved	[2]
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[1]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LY-334370	DM43O9N	Migraine	8A80	Phase 2	[3]

11 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1-naphthylpiperazine	DM6BIWK	Discovery agent	N.A.	Investigative	[1]
2-methyl-5-HT	DM1S5CB	N. A.	N. A.	Investigative	[4]
5-BODMT	DM7BWG5	Discovery agent	N.A.	Investigative	[5]
5-CT	DM260KD	Discovery agent	N.A.	Investigative	[1]
alpha-methyl-5-HT	DMCAYXF	Discovery agent	N.A.	Investigative	[4]
BRL-15572	DMM61Y2	Discovery agent	N.A.	Investigative	[6]
dipropyl-5-CT	DM9VKXC	Discovery agent	N.A.	Investigative	[4]
LY344864	DM8LSQP	Discovery agent	N.A.	Investigative	[7]
TFMPP	DMAC8TP	Discovery agent	N.A.	Investigative	[4]
WAY-466	DMMOH51	Discovery agent	N.A.	Investigative	[8]
[125I]LSD	DMP69QG	Discovery agent	N.A.	Investigative	[9]

References

• [1] Cloning and characterization of the guinea pig 5-HT1F receptor subtype: a comparison of the pharmacological profile to the human species homolog. Neuropharmacology. 1997 Apr-May;36(4-5):569-76.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [3] Selective seratonin 1F (5-HT(1F)) receptor agonist LY334370 for acute migraine: a randomised controlled trial. Lancet. 2001 Oct 13;358(9289):1230-4.
• [4] Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):408-12.
• [5] Toward selective drug development for the human 5-hydroxytryptamine 1E receptor: a comparison of 5-hydroxytryptamine 1E and 1F receptor structure-affinity relationships. J Pharmacol Exp Ther. 2011 Jun;337(3):860-7.
• [6] SB-216641 and BRL-15572--compounds to pharmacologically discriminate h5-HT1B and h5-HT1D receptors. Naunyn Schmiedebergs Arch Pharmacol. 1997 Sep;356(3):312-20.
• [7] 5-Hydroxytryptamine(1F) receptors do not participate in vasoconstriction: lack of vasoconstriction to LY344864, a selective serotonin(1F) receptor agonist in rabbit saphenous vein. J Pharmacol Exp Ther. 1999 Sep;290(3):935-9.
• [8] Discovery of 5-arylsulfonamido-3-(pyrrolidin-2-ylmethyl)-1H-indole derivatives as potent, selective 5-HT6 receptor agonists and antagonists. J Med Chem. 2005 Jan 27;48(2):353-6.
• [9] Isolation of a mouse "5HT1E-like" serotonin receptor expressed predominantly in hippocampus. J Biol Chem. 1992 Oct 5;267(28):19761-4.