Plasmodium falciparum histone deacetylase 1 | Antimalarial targets | IUPHAR/MMV Guide to MALARIA PHARMACOLOGY

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Plasmodium falciparum histone deacetylase 1

Target id: 3072

Nomenclature: Plasmodium falciparum histone deacetylase 1

Abbreviated Name: PfHDAC1

Family: Antimalarial targets

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

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
PfKDAC1
Database Links
ChEMBL Target
UniProtKB
Whole Organism Assay Data Linked to This Target
Key to terms and symbols Click column headers to sort
Ligand Sp. Assay description Type Action Value Parameter Reference
compound 1u [PMID: 30245402] PfDd2 Parasite growth inhibition assay - - 9.0 pIC50 2
pIC50 9.0 (IC50 1x10-9 M) [3H]-hypoxanthine incorporation [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
compound 1u [PMID: 30245402] Pf3D7 Parasite growth inhibition assay - - 8.4 pIC50 2
pIC50 8.4 (IC50 4x10-9 M) [3H]-hypoxanthine incorporation [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
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.
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 (see our HDACs Concise family page for more details). HDAC inhibitors have also emerged as potential therapies in a number of other disesases including malaria [1,3-4].

References

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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. 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]

3. 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]

4. 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]

How to cite this page

Antimalarial targets: Plasmodium falciparum histone deacetylase 1. Last modified on 26/03/2019. Accessed on 18/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3072.