Target Information
| Target General Information | Top | |||||
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| Target ID |
T78656
(Former ID: TTDR01194)
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| Target Name |
5-HT 1F receptor (HTR1F)
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| Synonyms |
Serotonin receptor 1F; HTR1EL; 5-hydroxytryptamine receptor 1F; 5-HT1F receptor; 5-HT1F; 5-HT-1F
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| Gene Name |
HTR1F
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Migraine [ICD-11: 8A80] | |||||
| 2 | Pituitary gland disorder [ICD-11: 5A60-5A61] | |||||
| 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).
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MDFLNSSDQNLTSEELLNRMPSKILVSLTLSGLALMTTTINSLVIAAIIVTRKLHHPANY
LICSLAVTDFLVAVLVMPFSIVYIVRESWIMGQVVCDIWLSVDITCCTCSILHLSAIALD RYRAITDAVEYARKRTPKHAGIMITIVWIISVFISMPPLFWRHQGTSRDDECIIKHDHIV STIYSTFGAFYIPLALILILYYKIYRAAKTLYHKRQASRIAKEEVNGQVLLESGEKSTKS VSTSYVLEKSLSDPSTDFDKIHSTVRSLRSEFKHEKSWRRQKISGTRERKAATTLGLILG AFVICWLPFFVKELVVNVCDKCKISEEMSNFLAWLGYLNSLINPLIYTIFNEDFKKAFQK LVRCRC Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| ADReCS ID | BADD_A06440 | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
| 1 | Lasmiditan | Drug Info | Approved | Migraine | [2] | |
| 2 | Metergolin | Drug Info | Approved | Hyperprolactinaemia | [3] | |
| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | LY-334370 | Drug Info | Phase 2 | Migraine | [4], [5] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Agonist | [+] 10 Agonist drugs | + | ||||
| 1 | Lasmiditan | Drug Info | [2] | |||
| 2 | 2-methyl-5-HT | Drug Info | [7] | |||
| 3 | 5-BODMT | Drug Info | [8] | |||
| 4 | 5-CT | Drug Info | [1] | |||
| 5 | alpha-methyl-5-HT | Drug Info | [7] | |||
| 6 | BRL-15572 | Drug Info | [9] | |||
| 7 | dipropyl-5-CT | Drug Info | [7] | |||
| 8 | LY344864 | Drug Info | [10] | |||
| 9 | TFMPP | Drug Info | [7] | |||
| 10 | [125I]LSD | Drug Info | [12] | |||
| Antagonist | [+] 2 Antagonist drugs | + | ||||
| 1 | Metergolin | Drug Info | [1] | |||
| 2 | 1-naphthylpiperazine | Drug Info | [1] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | LY-334370 | Drug Info | [6] | |||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | WAY-466 | Drug Info | [11] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Human Similarity Proteins
Human Pathway Affiliation
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| cAMP signaling pathway | hsa04024 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Serotonergic synapse | hsa04726 | Affiliated Target |
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| Class: Organismal Systems => Nervous system | Pathway Hierarchy | ||
| Taste transduction | hsa04742 | Affiliated Target |
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| Class: Organismal Systems => Sensory system | Pathway Hierarchy | ||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | cAMP signaling pathway | |||||
| 2 | Neuroactive ligand-receptor interaction | |||||
| 3 | Serotonergic synapse | |||||
| Panther Pathway | [+] 2 Panther Pathways | + | ||||
| 1 | Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway | |||||
| 2 | 5HT1 type receptor mediated signaling pathway | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Serotonin receptors | |||||
| 2 | G alpha (i) signalling events | |||||
| WikiPathways | [+] 6 WikiPathways | + | ||||
| 1 | Serotonin HTR1 Group and FOS Pathway | |||||
| 2 | Monoamine GPCRs | |||||
| 3 | GPCRs, Class A Rhodopsin-like | |||||
| 4 | GPCR ligand binding | |||||
| 5 | GPCR downstream signaling | |||||
| 6 | GPCRs, Other | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 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. | |||||
| REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019 | |||||
| REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 4 | 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. (Ligand id: 20). | |||||
| REF 5 | G-protein activation at 5-HT1A receptors by the 5-ht1F ligand LY334370 in guinea-pig brain sections and recombinant cell lines. Br J Pharmacol. 1998 May;124(2):283-90. | |||||
| REF 6 | Selective seratonin 1F (5-HT(1F)) receptor agonist LY334370 for acute migraine: a randomised controlled trial. Lancet. 2001 Oct 13;358(9289):1230-4. | |||||
| REF 7 | 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. | |||||
| REF 8 | 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. | |||||
| REF 9 | 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. | |||||
| REF 10 | 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. | |||||
| REF 11 | 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. | |||||
| REF 12 | Isolation of a mouse "5HT1E-like" serotonin receptor expressed predominantly in hippocampus. J Biol Chem. 1992 Oct 5;267(28):19761-4. | |||||
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