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Target id: 3072
Nomenclature: Plasmodium falciparum histone deacetylase 1
Abbreviated Name: PfHDAC1
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Plasmodium falciparum 3D7 | - | 449 | HDAC1 | histone deacetylase 1 |
Previous and Unofficial Names |
HDAC1 | Pf3D7_09_v3:1,028,046..1,031,647(-) | KDAC1 | PFI1260c |
Database Links | |
Alphafold | Q7K6A1 (Pf3D7) |
ChEMBL Target | CHEMBL1293190 (Pf3D7) |
PlasmoDB | PF3D7_0925700 (Pf3D7) |
UniProtKB | Q7K6A1 (Pf3D7) |
Whole Organism Assay Data Linked to This Target | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Malaria Pharmacology Comments |
The histone deacetylase (HDAC) family of enzymes are involved in the post-translational modification of histones by removal of acetyl groups from lysine residues. Removal of the acetyl groups facilitates tighter packing of chromatin (heterochromatin formation) leading to transcriptional repression. In humans, the 18 members of the HDAC family have been classified in to five subfamilies based on phylogenetic comparison with yeast homologues (see our HDACs Concise family page for more details). A recent review and analysis of the P. falciparum genome confirmed and classified the five known HDACs for this species of the parasite and identified a novel putative HDAC [7]: Class I contains PfHDAC1 Class II contains PfHDA1 and PfHDA2 Class III contains the sirtuin-like PfSir2A and PfSir2B PfCHD1 is a novel unclassified HDAC This family of enzymes has been shown to be involved in the regulation of a number of processes during development of the malaria parasite including schizogony, gemetocytogenesis , antigenic variation and hepatocyte invasion. HDACs have been identified as attractive molecular targets in the search for novel mechanisms to treat cancer and several small molecule HDAC inhibitors are already approved for clinical use. HDAC inhibitors have also emerged as potential therapies in a number of other disesases including malaria [1,4-5]. |
1. Andrews KT, Tran TN, Lucke AJ, Kahnberg P, Le GT, Boyle GM, Gardiner DL, Skinner-Adams TS, Fairlie DP. (2008) Potent antimalarial activity of histone deacetylase inhibitor analogues. Antimicrob Agents Chemother, 52 (4): 1454-61. [PMID:18212103]
2. Chua MJ, Arnold MS, Xu W, Lancelot J, Lamotte S, Späth GF, Prina E, Pierce RJ, Fairlie DP, Skinner-Adams TS et al.. (2017) Effect of clinically approved HDAC inhibitors on Plasmodium, Leishmania and Schistosoma parasite growth. Int J Parasitol Drugs Drug Resist, 7 (1): 42-50. [PMID:28107750]
3. Diedrich D, Stenzel K, Hesping E, Antonova-Koch Y, Gebru T, Duffy S, Fisher G, Schöler A, Meister S, Kurz T et al.. (2018) One-pot, multi-component synthesis and structure-activity relationships of peptoid-based histone deacetylase (HDAC) inhibitors targeting malaria parasites. Eur J Med Chem, 158: 801-813. [PMID:30245402]
4. Engel JA, Jones AJ, Avery VM, Sumanadasa SD, Ng SS, Fairlie DP, Skinner-Adams T, Andrews KT. (2015) Profiling the anti-protozoal activity of anti-cancer HDAC inhibitors against Plasmodium and Trypanosoma parasites. Int J Parasitol Drugs Drug Resist, 5 (3): 117-26. [PMID:26199860]
5. Hansen FK, Sumanadasa SD, Stenzel K, Duffy S, Meister S, Marek L, Schmetter R, Kuna K, Hamacher A, Mordmüller B et al.. (2014) Discovery of HDAC inhibitors with potent activity against multiple malaria parasite life cycle stages. Eur J Med Chem, 82: 204-13. [PMID:24904967]
6. Huang Z, Li R, Tang T, Ling D, Wang M, Xu D, Sun M, Zheng L, Zhu F, Min H et al.. (2020) A novel multistage antiplasmodial inhibitor targeting Plasmodium falciparum histone deacetylase 1. Cell Discov, 6 (1): 93. [PMID:33311461]
7. Kanyal A, Rawat M, Gurung P, Choubey D, Anamika K, Karmodiya K. (2018) Genome-wide survey and phylogenetic analysis of histone acetyltransferases and histone deacetylases of Plasmodium falciparum. FEBS J, 285 (10): 1767-1782. [PMID:29284196]
8. Mackwitz MKW, Hesping E, Antonova-Koch Y, Diedrich D, Woldearegai TG, Skinner-Adams T, Clarke M, Schöler A, Limbach L, Kurz T et al.. (2019) Structure-Activity and Structure-Toxicity Relationships of Peptoid-Based Histone Deacetylase Inhibitors with Dual-Stage Antiplasmodial Activity. ChemMedChem, 14 (9): 912-926. [PMID:30664827]
9. Potluri V, Shandil RK, Gavara R, Sambasivam G, Campo B, Wittlin S, Narayanan S. (2020) Discovery of FNDR-20123, a histone deacetylase inhibitor for the treatment of Plasmodium falciparum malaria. Malar J, 19 (1): 365. [PMID:33046062]
10. Sun W, Tanaka TQ, Magle CT, Huang W, Southall N, Huang R, Dehdashti SJ, McKew JC, Williamson KC, Zheng W. (2014) Chemical signatures and new drug targets for gametocytocidal drug development. Sci Rep, 4: 3743. [PMID:24434750]
11. Wang M, Tang T, Li R, Huang Z, Ling D, Zheng L, Ding Y, Liu T, Xu W, Zhu F et al.. (2022) Drug Repurposing of Quisinostat to Discover Novel Plasmodium falciparum HDAC1 Inhibitors with Enhanced Triple-Stage Antimalarial Activity and Improved Safety. J Med Chem, 65 (5): 4156-4181. [PMID:35175762]
Chromatin modifying enzymes (Plasmodium spp.): Plasmodium falciparum histone deacetylase 1. Last modified on 30/03/2022. Accessed on 11/11/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3072.