Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T36935
(Former ID: TTDR00503)
|
|||||
| Target Name |
Prostate specific antigen (KLK3)
|
|||||
| Synonyms |
Seminin; Semenogelase; Prostate-specific antigen; PSA; P-30 antigen; Kallikrein-3; Gamma-seminoprotein; APS
Click to Show/Hide
|
|||||
| Gene Name |
KLK3
|
|||||
| Target Type |
Clinical trial target
|
[1] | ||||
| Disease | [+] 3 Target-related Diseases | + | ||||
| 1 | Arteries/arterioles disorder [ICD-11: BD52] | |||||
| 2 | Prostate cancer [ICD-11: 2C82] | |||||
| 3 | Prostate hyperplasia [ICD-11: GA90] | |||||
| Function |
Hydrolyzes semenogelin-1 thus leading to the liquefaction of the seminal coagulum.
Click to Show/Hide
|
|||||
| BioChemical Class |
Peptidase
|
|||||
| UniProt ID | ||||||
| EC Number |
EC 3.4.21.77
|
|||||
| Sequence |
MWVPVVFLTLSVTWIGAAPLILSRIVGGWECEKHSQPWQVLVASRGRAVCGGVLVHPQWV
LTAAHCIRNKSVILLGRHSLFHPEDTGQVFQVSHSFPHPLYDMSLLKNRFLRPGDDSSHD LMLLRLSEPAELTDAVKVMDLPTQEPALGTTCYASGWGSIEPEEFLTPKKLQCVDLHVIS NDVCAQVHPQKVTKFMLCAGRWTGGKSTCSGDSGGPLVCNGVLQGITSWGSEPCALPERP SLYTKVVHYRKWIKDTIVANP Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T61HH0 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Clinical Trial Drug(s) | [+] 6 Clinical Trial Drugs | + | ||||
| 1 | Motexafin lutetium | Drug Info | Phase 3 | Artery stenosis | [1] | |
| 2 | ProstaVac | Drug Info | Phase 3 | Prostate hyperplasia | [2] | |
| 3 | PRX-302 | Drug Info | Phase 3 | Prostate cancer | [3] | |
| 4 | Rilimogene galvacirepvec | Drug Info | Phase 3 | Prostate cancer | [4] | |
| 5 | ADXS-PSA | Drug Info | Phase 1/2 | Prostate cancer | [5], [6], [7] | |
| 6 | MVA-BN Breast | Drug Info | Phase 1 | Prostate cancer | [8] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Modulator | [+] 6 Modulator drugs | + | ||||
| 1 | Motexafin lutetium | Drug Info | [1] | |||
| 2 | PRX-302 | Drug Info | [10] | |||
| 3 | Rilimogene galvacirepvec | Drug Info | [4] | |||
| 4 | ADXS-PSA | Drug Info | [9] | |||
| 5 | ProstaRex | Drug Info | [9] | |||
| 6 | VTT-201 | Drug Info | [9] | |||
| Antagonist | [+] 1 Antagonist drugs | + | ||||
| 1 | MVA-BN Breast | Drug Info | [11], [12] | |||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | PMID23692593C20 | Drug Info | [13] | |||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: 2-(Acetylamino)-2-Deoxy-a-D-Glucopyranose | Ligand Info | |||||
| Structure Description | Crystal structure of human prostate specific antigen complexed with an activating antibody | PDB:2ZCH | ||||
| Method | X-ray diffraction | Resolution | 2.83 Å | Mutation | No | [14] |
| PDB Sequence |
IVGGWECEKH
25 SQPWQVLVAS35 RGRAVCGGVL46 VHPQWVLTAA56 HCIRNKSVIL66 LGRHSLFHPE 77 DTGQVFQVSH87 SFPHPLYDMS95B LLKNRFLRPG96 DDSSHDLMLL106 RLSEPAELTD 116 AVKVMDLPTQ128 EPALGTTCYA138 SGWGSIEPEE148 FLTPKKLQCV158 DLHVISNDVC 168 AQVHPQKVTK178 FMLCAGRWTG186B GKSTCSGDSG196 GPLVCNGVLQ210 GITSWGSEPC 220 ALPERPSLYT229 KVVHYRKWIK239 DTIVANP
|
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| 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 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).
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
Biological Network Descriptors
|
|
|
There is no similarity protein (E value < 0.005) for this target
|
|
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.
|
| Degree | 6 | Degree centrality | 6.45E-04 | Betweenness centrality | 3.11E-04 |
|---|---|---|---|---|---|
| Closeness centrality | 2.21E-01 | Radiality | 1.39E+01 | Clustering coefficient | 6.67E-02 |
| Neighborhood connectivity | 2.30E+01 | Topological coefficient | 1.82E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-regulating Transcription Factors | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Pathways in cancer | |||||
| 2 | Prostate cancer | |||||
| PID Pathway | [+] 3 PID Pathways | + | ||||
| 1 | Coregulation of Androgen receptor activity | |||||
| 2 | Regulation of Androgen receptor activity | |||||
| 3 | FOXA1 transcription factor network | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) | |||||
| 2 | Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 | |||||
| WikiPathways | [+] 2 WikiPathways | + | ||||
| 1 | Prostate Cancer | |||||
| 2 | Androgen receptor signaling pathway | |||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Motexafin lutetium-photodynamic therapy of prostate cancer: short- and long-term effects on prostate-specific antigen. Clin Cancer Res. 2008 Aug 1;14(15):4869-76. | |||||
| REF 2 | Prostvac-VF: a vector-based vaccine targeting PSA in prostate cancer. Expert Opin Investig Drugs. 2009 July; 18(7): 1001-1011. | |||||
| REF 3 | ClinicalTrials.gov (NCT01966614) Randomized, Double-Blind, Vehicle-Controlled, Multicenter Safety and Efficacy Study of Intraprostatic PRX302 for LUTS BPH. U.S. National Institutes of Health. | |||||
| REF 4 | Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol. 2010 Mar 1;28(7):1099-105. | |||||
| REF 5 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 6 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 7 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 8 | ClinicalTrials.gov (NCT00629057) A Safety Trial of MVA-BN-PRO in Men With Androgen-Insensitive Prostate Cancer. U.S. National Institutes of Health. | |||||
| REF 9 | 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. (Target id: 2373). | |||||
| REF 10 | Phase 1 and 2 studies demonstrate the safety and efficacy of intraprostatic injection of PRX302 for the targeted treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. Eur Urol. 2011 May;59(5):747-54. | |||||
| REF 11 | Exosome targeting of tumor antigens expressed by cancer vaccines can improve antigen immunogenicity and therapeutic efficacy. Cancer Res. 2011 Aug 1;71(15):5235-44. | |||||
| REF 12 | J Clin Oncol 31, 2013 (suppl 6; abstr 193). | |||||
| REF 13 | Structural optimization, biological evaluation, and application of peptidomimetic prostate specific antigen inhibitors. J Med Chem. 2013 Jun 13;56(11):4224-35. | |||||
| REF 14 | Crystal structure of a ternary complex between human prostate-specific antigen, its substrate acyl intermediate and an activating antibody. J Mol Biol. 2008 Feb 29;376(4):1021-33. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.