Target Information
Target General Information | Top | |||||
---|---|---|---|---|---|---|
Target ID |
T73696
(Former ID: TTDI02307)
|
|||||
Target Name |
Relaxin receptor 1 (RXFP1)
|
|||||
Synonyms |
Relaxin family peptide receptor 1; RXFP1; Leucine-rich repeat-containing G-protein coupled receptor 7
Click to Show/Hide
|
|||||
Gene Name |
RXFP1
|
|||||
Target Type |
Clinical trial target
|
[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Heart failure [ICD-11: BD10-BD1Z] | |||||
Function |
Receptor for relaxins. The activity of this receptor is mediated by G proteins leading to stimulation of adenylate cyclase and an increase of cAMP. Binding of the ligand may also activate a tyrosine kinase pathway that inhibits the activity of a phosphodiesterase that degrades cAMP.
Click to Show/Hide
|
|||||
BioChemical Class |
GPCR rhodopsin
|
|||||
UniProt ID | ||||||
Sequence |
MTSGSVFFYILIFGKYFSHGGGQDVKCSLGYFPCGNITKCLPQLLHCNGVDDCGNQADED
NCGDNNGWSLQFDKYFASYYKMTSQYPFEAETPECLVGSVPVQCLCQGLELDCDETNLRA VPSVSSNVTAMSLQWNLIRKLPPDCFKNYHDLQKLYLQNNKITSISIYAFRGLNSLTKLY LSHNRITFLKPGVFEDLHRLEWLIIEDNHLSRISPPTFYGLNSLILLVLMNNVLTRLPDK PLCQHMPRLHWLDLEGNHIHNLRNLTFISCSNLTVLVMRKNKINHLNENTFAPLQKLDEL DLGSNKIENLPPLIFKDLKELSQLNLSYNPIQKIQANQFDYLVKLKSLSLEGIEISNIQQ RMFRPLMNLSHIYFKKFQYCGYAPHVRSCKPNTDGISSLENLLASIIQRVFVWVVSAVTC FGNIFVICMRPYIRSENKLYAMSIISLCCADCLMGIYLFVIGGFDLKFRGEYNKHAQLWM ESTHCQLVGSLAILSTEVSVLLLTFLTLEKYICIVYPFRCVRPGKCRTITVLILIWITGF IVAFIPLSNKEFFKNYYGTNGVCFPLHSEDTESIGAQIYSVAIFLGINLAAFIIIVFSYG SMFYSVHQSAITATEIRNQVKKEMILAKRFFFIVFTDALCWIPIFVVKFLSLLQVEIPGT ITSWVVIFILPINSALNPILYTLTTRPFKEMIHRFWYNYRQRKSMDSKGQKTYAPSFIWV EMWPLQEMPPELMKPDLFTYPCEMSLISQSTRLNSYS Click to Show/Hide
|
|||||
3D Structure | Click to Show 3D Structure of This Target | AlphaFold |
Drugs and Modes of Action | Top | |||||
---|---|---|---|---|---|---|
Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
1 | RLX030 | Drug Info | Approval submitted | Acute heart failure | [2] | |
2 | AZD5462 | Drug Info | Phase 1 | Cardiovascular disease | [3] | |
Mode of Action | [+] 3 Modes of Action | + | ||||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | RLX030 | Drug Info | [1] | |||
Agonist | [+] 1 Agonist drugs | + | ||||
1 | AZD5462 | Drug Info | [4] | |||
Modulator (allosteric modulator) | [+] 1 Modulator (allosteric modulator) drugs | + | ||||
1 | ML290 | Drug Info | [5] |
Cell-based Target Expression Variations | Top | |||||
---|---|---|---|---|---|---|
Cell-based Target Expression Variations |
Different Human System Profiles of Target | Top |
---|---|
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).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
|
KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
---|---|---|---|
Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
|
Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
Relaxin signaling pathway | hsa04926 | Affiliated Target |
|
Class: Organismal Systems => Endocrine system | Pathway Hierarchy |
Degree | 7 | Degree centrality | 7.52E-04 | Betweenness centrality | 7.12E-08 |
---|---|---|---|---|---|
Closeness centrality | 1.41E-01 | Radiality | 1.16E+01 | Clustering coefficient | 5.24E-01 |
Neighborhood connectivity | 4.86E+00 | Topological coefficient | 6.07E-01 | Eccentricity | 14 |
Download | Click to Download the Full PPI Network of This Target | ||||
Chemical Structure based Activity Landscape of Target | Top |
---|---|
Target Poor or Non Binders | Top | |||||
---|---|---|---|---|---|---|
Target Poor or Non Binders |
References | Top | |||||
---|---|---|---|---|---|---|
REF 1 | Design of the RELAXin in acute heart failure study. Am Heart J. 2012 Feb;163(2):149-55.e1. | |||||
REF 2 | Clinical pipeline report, company report or official report of Novartis. | |||||
REF 3 | ClinicalTrials.gov (NCT05512806) A Randomized, 6-period, 6-treatment, Single-Dose, Crossover Study to Assess the Pharmacokinetics of AZD5462 Film-coated Tablet Formulation, to Assess the Relative Bioavailability of AZD5462 Film-coated Tablet Formulation vs Oral Solution, and to Assess the Influence of Food on the Pharmacokinetics of AZD5462 in Healthy Participants. U.S.National Institutes of Health. | |||||
REF 4 | Clinical pipeline report, company report or official report of AstraZeneca | |||||
REF 5 | Discovery, optimization, and biological activity of the first potent and selective small-molecule agonist series of human relaxin receptor 1 (RXFP1). Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010. |
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.