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perforin 1

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 3100

Nomenclature: perforin 1

Family: Cytolytic pore-forming proteins

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 555 10q22.1 PRF1 perforin 1 2
Previous and Unofficial Names Click here for help
cytolysin | lymphocyte pore-forming protein | perforin-1
Database Links Click here for help
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein

Download all structure-activity data for this target as a CSV file go icon to follow link

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 16 [PMID: 31525966] Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 5.3 pIC50 8
pIC50 5.3 (IC50 4.43x10-6 M) [8]
Description: Inhibition of perforin-mediated lysis of 51Cr-loaded K562 target cells in the presence of KHYG1 human NK cells. Measured as release of 51Cr.
Immunopharmacology Comments
Perforin 1 is expressed only in the secretory granules of cytotoxic T cells and natural killer (NK) cells, and it is an essential component of the immune system. These cell types release perforin 1 close to target cells (e.g. virus-infected and neoplastic cells) in process known as the granule exocytosis pathway [1]. The released perforin 1 monomers rapidly oligomerise to form pores that penetrate the target cells and allow entry of pro-apoptopic granzymes into the target cell cytosol to trigger target cell death [4].

Small molecule inhibitors of perforin 1 function are predicted to exhibit immunosuppressive activity, and medicinal chemists are working to design drug-like perforin inhibitors [5-10,12].
Cell Type Associations
Immuno Cell Type:  T cells
Cell Ontology Term:   cytotoxic T cell (CL:0000910)
References:  4
Immuno Cell Type:  Natural killer cells
Cell Ontology Term:   natural killer cell (CL:0000623)
References:  4
Immuno Process Associations
Immuno Process:  B cell (activation)
Immuno Process:  Cellular signalling
Immuno Process:  T cell (activation)
Gene Expression and Pathophysiology Comments
Mutations in the PRF1 gene, that reduce levels of functional perforin 1 protein, cause familial hemophagocytic lymphohistiocytosis 2 (FHL2) [3,11], which is a rare autosomal recessive immune disorder (onset in infancy or early childhood) that is characterised by immune dysregulation (uncontrolled activation of T cells and macrophages) with hypercytokinemia (overproduction of inflammatory cytokines), and reduced activity of cytotoxic T and natural killer cells. FHL is genetically heterogeneic, and defects in other genes or at different chromosomal locations underlie the various disease subclasses (FHL1-5).


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1. de Saint Basile G, Ménasché G, Fischer A. (2010) Molecular mechanisms of biogenesis and exocytosis of cytotoxic granules. Nat Rev Immunol, 10 (8): 568-79. [PMID:20634814]

2. Fink TM, Zimmer M, Weitz S, Tschopp J, Jenne DE, Lichter P. (1992) Human perforin (PRF1) maps to 10q22, a region that is syntenic with mouse chromosome 10. Genomics, 13 (4): 1300-2. [PMID:1505959]

3. Göransdotter Ericson K, Fadeel B, Nilsson-Ardnor S, Söderhäll C, Samuelsson A, Janka G, Schneider M, Gürgey A, Yalman N, Révész T et al.. (2001) Spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis. Am J Hum Genet, 68 (3): 590-7. [PMID:11179007]

4. Law RH, Lukoyanova N, Voskoboinik I, Caradoc-Davies TT, Baran K, Dunstone MA, D'Angelo ME, Orlova EV, Coulibaly F, Verschoor S et al.. (2010) The structural basis for membrane binding and pore formation by lymphocyte perforin. Nature, 468 (7322): 447-51. [PMID:21037563]

5. Miller CK, Huttunen KM, Denny WA, Jaiswal JK, Ciccone A, Browne KA, Trapani JA, Spicer JA. (2016) Diarylthiophenes as inhibitors of the pore-forming protein perforin. Bioorg Med Chem Lett, 26 (2): 355-360. [PMID:26711151]

6. Spicer JA, Huttunen KM, Jose J, Dimitrov I, Akhlaghi H, Sutton VR, Voskoboinik I, Trapani J. (2022) Small Molecule Inhibitors of Lymphocyte Perforin as Focused Immunosuppressants for Infection and Autoimmunity. J Med Chem, 65 (21): 14305-14325. [PMID:36263926]

7. Spicer JA, Lena G, Lyons DM, Huttunen KM, Miller CK, O'Connor PD, Bull M, Helsby N, Jamieson SM, Denny WA et al.. (2013) Exploration of a series of 5-arylidene-2-thioxoimidazolidin-4-ones as inhibitors of the cytolytic protein perforin. J Med Chem, 56 (23): 9542-55. [PMID:24195776]

8. Spicer JA, Miller CK, O'Connor PD, Jose J, Giddens AC, Jaiswal JK, Jamieson SMF, Bull MR, Denny WA, Akhlaghi H et al.. (2020) Inhibition of the Cytolytic Protein Perforin Prevents Rejection of Transplanted Bone Marrow Stem Cells in Vivo. J Med Chem, 63 (5): 2229-2239. [PMID:31525966]

9. Spicer JA, Miller CK, O'Connor PD, Jose J, Huttunen KM, Jaiswal JK, Denny WA, Akhlaghi H, Browne KA, Trapani JA. (2017) Benzenesulphonamide inhibitors of the cytolytic protein perforin. Bioorg Med Chem Lett, 27 (4): 1050-1054. [PMID:28110869]

10. Spicer JA, Miller CK, O'Connor PD, Jose J, Huttunen KM, Jaiswal JK, Denny WA, Akhlaghi H, Browne KA, Trapani JA. (2017) Substituted arylsulphonamides as inhibitors of perforin-mediated lysis. Eur J Med Chem, 137: 139-155. [PMID:28582670]

11. Stepp SE, Dufourcq-Lagelouse R, Le Deist F, Bhawan S, Certain S, Mathew PA, Henter JI, Bennett M, Fischer A, de Saint Basile G et al.. (1999) Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science, 286 (5446): 1957-9. [PMID:10583959]

12. Welz M, Eickhoff S, Abdullah Z, Trebicka J, Gartlan KH, Spicer JA, Demetris AJ, Akhlaghi H, Anton M, Manske K et al.. (2018) Perforin inhibition protects from lethal endothelial damage during fulminant viral hepatitis. Nat Commun, 9 (1): 4805. [PMID:30442932]

How to cite this page

Cytolytic pore-forming proteins: perforin 1. Last modified on 21/10/2022. Accessed on 19/06/2024. IUPHAR/BPS Guide to PHARMACOLOGY,