Target Information
Target General Information | Top | |||||
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Target ID |
T83905
(Former ID: TTDI02034)
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Target Name |
Placental cadherin (CDH3)
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Synonyms |
Pcadherin; P-cadherin; Cadherin-3; CDHP
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Gene Name |
CDH3
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
Function |
Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.
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BioChemical Class |
Cadherin protein
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UniProt ID | ||||||
Sequence |
MGLPRGPLASLLLLQVCWLQCAASEPCRAVFREAEVTLEAGGAEQEPGQALGKVFMGCPG
QEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPISVPENG KGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKPLDREEIAK YELFGHAVSENGASVEDPMNISIIVTDQNDHKPKFTQDTFRGSVLEGVLPGTSVMQVTAT DEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDREKVPEYTLTIQA TDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGHEVQRLTVTDLDAPNSP AWRATYLIMGGDDGDHFTITTHPESNQGILTTRKGLDFEAKNQHTLYVEVTNEAPFVLKL PTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPVCVYTAEDPDKENQKISYRILR DPAGWLAMDPDSGQVTAVGTLDREDEQFVRNNIYEVMVLAMDNGSPPTTGTGTLLLTLID VNDHGPVPEPRQITICNQSPVRQVLNITDKDLSPHTSPFQAQLTDDSDIYWTAEVNEEGD TVVLSLKKFLKQDTYDVHLSLSDHGNKEQLTVIRATVCDCHGHVETCPGPWKGGFILPVL GAVLALLFLLLVLLLLVRKKRKIKEPLLLPEDDTRDNVFYYGEEGGGEEDQDYDITQLHR GLEARPEVVLRNDVAPTIIPTPMYRPRPANPDEIGNFIIENLKAANTDPTAPPYDTLLVF DYEGSGSDAASLSSLTSSASDQDQDYDYLNEWGSRFKKLADMYGGGEDD Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
1 | PF-06671008 | Drug Info | Phase 1 | Solid tumour/cancer | [2] | |
2 | PF-3732010 | Drug Info | Phase 1 | Solid tumour/cancer | [3] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Immunomodulator | [+] 1 Immunomodulator drugs | + | ||||
1 | PF-06671008 | Drug Info | [4] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Drug Binding Sites of Target | Top | |||||
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Ligand Name: 2-(5-chloro-2-methyl-1H-indol-3-yl)ethanamine | Ligand Info | |||||
Structure Description | Crystal structure of human P-cadherin REC12 (monomer) in complex with 2-(5-chloro-2-methyl-1H-indol-3-yl)ethan-1-amine (inhibitor) | PDB:7CMF | ||||
Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [5] |
PDB Sequence |
WVVAPISVPE
11 NGKGPFPQRL21 NQLKSNKDRD31 TKIFYSITGP41 GADSPPEGVF51 AVEKETGWLL 61 LNKPLDREEI71 AKYELFGHAV81 SENGASVEDP91 MNISIIVTDQ101 NDHKPKFTQD 111 TFRGSVLEGV121 LPGTSVMQVT131 ATDEDDAIYT141 YNGVVAYSIH151 SQEPKDPHDL 161 MFTIHRSTGT171 ISVISSGLDR181 EKVPEYTLTI191 QATDMDGDGS201 TTTAVAVVEI 211 LD
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Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
Click to View More Binding Site Information of This Target with Different Ligands |
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 Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
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 Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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Cell adhesion molecules | hsa04514 | Affiliated Target |
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Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy |
Degree | 2 | Degree centrality | 2.15E-04 | Betweenness centrality | 0.00E+00 |
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Closeness centrality | 2.23E-01 | Radiality | 1.39E+01 | Clustering coefficient | 1.00E+00 |
Neighborhood connectivity | 1.19E+02 | Topological coefficient | 5.53E-01 | Eccentricity | 12 |
Download | Click to Download the Full PPI Network of This Target | ||||
Target Regulators | Top | |||||
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Target-interacting Proteins |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
1 | Cell adhesion molecules (CAMs) | |||||
Panther Pathway | [+] 3 Panther Pathways | + | ||||
1 | Alzheimer disease-presenilin pathway | |||||
2 | Cadherin signaling pathway | |||||
3 | Wnt signaling pathway | |||||
Reactome | [+] 1 Reactome Pathways | + | ||||
1 | Adherens junctions interactions | |||||
WikiPathways | [+] 2 WikiPathways | + | ||||
1 | Hair Follicle Development: Induction (Part 1 of 3) | |||||
2 | Cell junction organization |
References | Top | |||||
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REF 1 | National Cancer Institute Drug Dictionary (drug id 580366). | |||||
REF 2 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
REF 3 | ClinicalTrials.gov (NCT00557505) A Study Of PF-03732010 In Patients With Advanced Solid Tumors. U.S. National Institutes of Health. | |||||
REF 4 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
REF 5 | Regulation of cadherin dimerization by chemical fragments as a trigger to inhibit cell adhesion. doi:10.1038/s42003-021-02575-3. |
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