Target Information
| Target General Information | Top | |||||
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| Target ID |
T69823
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| Target Name |
P53 Y220C mutant (TP53 Y220C)
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| Gene Name |
TP53
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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] | |||||
| UniProt ID | ||||||
| Sequence |
MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGP
DEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAK SVTCTYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAMAIYKQSQHMTEVVRRCPHHE RCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNS SCMGGMNRRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHELP PGSTKRALPNNTSSSPQPKKKPLDGEYFTLQIRGRERFEMFRELNEALELKDAQAGKEPG GSRAHSSHLKSKKGQSTSRHKKLMFKTEGPDSD Click to Show/Hide
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| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | PC14586 | Drug Info | Phase 1/2 | Solid tumour/cancer | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Reactivator | [+] 1 Reactivator drugs | + | ||||
| 1 | PC14586 | Drug Info | [1] | |||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: 1-(2-Methylpropanoyl)indole-3-carbaldehyde | Ligand Info | |||||
| Structure Description | Crystal structure of p53 Y220C covalently bound to indole KG6 | PDB:8DC6 | ||||
| Method | X-ray diffraction | Resolution | 1.60 Å | Mutation | Yes | [3] |
| PDB Sequence |
AHMSSSVPSQ
100 KTYQGSYGFR110 LGFLHVTSTY126 SPALNKLFCQ136 LAKTCPVQLW146 VDSTPPPGTR 156 VRAMAIYKQS166 QHMTEVVRRC176 PHHERSSDSD186 GLAPPQHLIR196 VEGNLRVEYL 206 DDRNTFRHSV216 VVPCEPPEVG226 SDSTTIHYNY236 MCYSSCMGGM246 NRRPILTIIT 256 LEDSSGNLLG266 RDSFEVRVSA276 SPGRDRRTEE286 ENL
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| Ligand Name: 9-propanoyl-9H-carbazole-3-carbaldehyde, bound form | Ligand Info | |||||
| Structure Description | Crystal structure of p53 Y220C covalently bound to carbazole KG3 | PDB:8DC4 | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | Yes | [3] |
| PDB Sequence |
MSSSVPSQKT
102 YQGSYGFRLG112 FLHSGTAKSV122 TSTYSPALNK132 LFCQLAKTCP142 VQLWVDSTPP 152 PGTRVRAMAI162 YKQSQHMTEV172 VRRCPHHERS182 SDSDGLAPPQ192 HLIRVEGNLR 202 VEYLDDRNTF212 RHSVVVPCEP222 PEVGSDSTTI232 HYNYMCYSSC242 MGGMNRRPIL 252 TIITLEDSSG262 NLLGRDSFEV272 RVSASPGRDR282 RTEEENL
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| 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 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 Pathway Affiliation
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| MAPK signaling pathway | hsa04010 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Sphingolipid signaling pathway | hsa04071 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Cell cycle | hsa04110 | Affiliated Target |
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| Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
| p53 signaling pathway | hsa04115 | Affiliated Target |
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| Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
| Mitophagy - animal | hsa04137 | Affiliated Target |
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| Class: Cellular Processes => Transport and catabolism | Pathway Hierarchy | ||
| PI3K-Akt signaling pathway | hsa04151 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Apoptosis | hsa04210 | Affiliated Target |
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| Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
| Longevity regulating pathway | hsa04211 | Affiliated Target |
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| Class: Organismal Systems => Aging | Pathway Hierarchy | ||
| Ferroptosis | hsa04216 | Affiliated Target |
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| Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
| Cellular senescence | hsa04218 | Affiliated Target |
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| Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
| Wnt signaling pathway | hsa04310 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Neurotrophin signaling pathway | hsa04722 | Affiliated Target |
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| Class: Organismal Systems => Nervous system | Pathway Hierarchy | ||
| Thyroid hormone signaling pathway | hsa04919 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Click to Show/Hide the Information of Affiliated Human Pathways | |||
| References | Top | |||||
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| REF 1 | Clinical pipeline report, company report or official report of PMV Pharmaceuticals. | |||||
| REF 2 | ClinicalTrials.gov (NCT04585750) The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a p53 Y220C Mutation. U.S. National Institutes of Health. | |||||
| REF 3 | A Small Molecule Reacts with the p53 Somatic Mutant Y220C to Rescue Wild-type Thermal Stability. Cancer Discov. 2023 Jan 9;13(1):56-69. | |||||
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