Target Information
Target General Information | Top | |||||
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Target ID |
T16308
(Former ID: TTDR00355)
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Target Name |
Rotamase Pin1 (PIN1)
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Synonyms |
Prolyl isomerase Pin1; Peptidyl-prolyl cis-trans isomerase Pin1; Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1; Peptidyl prolyl cis/trans isomerase Pin1; PPIase Pin1
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Gene Name |
PIN1
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Lung cancer [ICD-11: 2C25] | |||||
Function |
By inducing conformational changes in a subset of phosphorylated proteins, acts as a molecular switch in multiple cellular processes (, Ref. 21). Displays a preference for acidic residues located N-terminally to the proline bond to be isomerized. Regulates mitosis presumably by interacting with NIMA and attenuating its mitosis-promoting activity. Down-regulates kinase activity of BTK. Can transactivate multiple oncogenes and induce centrosome amplification, chromosome instability and cell transformation. Required for the efficient dephosphorylation and recycling of RAF1 after mitogen activation. Binds and targets PML and BCL6 for degradation in a phosphorylation-dependent manner. Acts as a regulator of JNK cascade by binding to phosphorylated FBXW7, disrupting FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation: degradation of FBXW7 leads to subsequent stabilization of JUN. May facilitate the ubiquitination and proteasomal degradation of RBBP8/CtIP through CUL3/KLHL15 E3 ubiquitin-protein ligase complex, hence favors DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR). Peptidyl-prolyl cis/trans isomerase (PPIase) that binds to and isomerizes specific phosphorylated Ser/Thr-Pro (pSer/Thr-Pro) motifs.
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BioChemical Class |
Cis-trans-isomerase
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UniProt ID | ||||||
EC Number |
EC 5.2.1.8
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Sequence |
MADEEKLPPGWEKRMSRSSGRVYYFNHITNASQWERPSGNSSSGGKNGQGEPARVRCSHL
LVKHSQSRRPSSWRQEKITRTKEEALELINGYIQKIKSGEEDFESLASQFSDCSSAKARG DLGAFSRGQMQKPFEDASFALRTGEMSGPVFTDSGIHIILRTE Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
HIT2.0 ID | T20OEM |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | Avastin+/-Tarceva | Drug Info | Phase 3 | Non-small-cell lung cancer | [2] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 11 Inhibitor drugs | + | ||||
1 | Avastin+/-Tarceva | Drug Info | [1] | |||
2 | (R)-2-(2-naphthamido)-3-m-tolylpropanoic acid | Drug Info | [3] | |||
3 | (R)-2-(2-naphthamido)-3-p-tolylpropanoic acid | Drug Info | [3] | |||
4 | (R)-2-(2-naphthamido)-5-phenylpent-4-ynoic acid | Drug Info | [3] | |||
5 | (R)-3-(2-naphthamido)-4-m-tolylbutanoic acid | Drug Info | [3] | |||
6 | (R,)-2-(2-naphthamido)-5-phenylpent-4-enoic acid | Drug Info | [3] | |||
7 | 3,6,9,12,15,18-HEXAOXAICOSANE | Drug Info | [4] | |||
8 | Ac-Bth-Thr(PO3H2)-Pip-Nal-Gln-NH2 | Drug Info | [5] | |||
9 | Ac-Phe-D-Thr(PO3H2)-Pip-Nal-Gln-NH2 | Drug Info | [5] | |||
10 | Ac-Phe-Thr(PO3H2)-Pip-Nal-Gln-NH2 | Drug Info | [5] | |||
11 | Beta-(2-Naphthyl)-Alanine | Drug Info | [4] |
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 Regulators | Top | |||||
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Target-regulating microRNAs | ||||||
Target-interacting Proteins |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
1 | RIG-I-like receptor signaling pathway | |||||
PID Pathway | [+] 4 PID Pathways | + | ||||
1 | p73 transcription factor network | |||||
2 | C-MYC pathway | |||||
3 | PDGFR-beta signaling pathway | |||||
4 | p53 pathway | |||||
Reactome | [+] 2 Reactome Pathways | + | ||||
1 | ISG15 antiviral mechanism | |||||
2 | Negative regulators of RIG-I/MDA5 signaling | |||||
WikiPathways | [+] 2 WikiPathways | + | ||||
1 | ISG15 antiviral mechanism | |||||
2 | RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | Overexpression of PIN1 Enhances Cancer Growth and Aggressiveness with Cyclin D1 Induction in EBV-Associated Nasopharyngeal Carcinoma.PLoS One. 2016 Jun 3;11(6):e0156833. | |||||
REF 2 | Clinical pipeline report, company report or official report of Roche. | |||||
REF 3 | Structure-based design of novel human Pin1 inhibitors (II). Bioorg Med Chem Lett. 2010 Apr 1;20(7):2210-4. | |||||
REF 4 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
REF 5 | Nanomolar inhibitors of the peptidyl prolyl cis/trans isomerase Pin1 from combinatorial peptide libraries. J Med Chem. 2006 Apr 6;49(7):2147-50. |
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