Hidroksikarbamid (INN ) ili hidroksiureja (Hydrea i Droxia ) je antineoplastični lek , koji je prvi put sintetisan 1869 . godine. On se koristi za tretman mijeloproliferativnih poremećaja , posebno slučajeva bolesti policitemija vera i esencijalna trombocitemija . Takođe se koristi za ublažavanje bolnih napada uzrokovanih srpastom anemijom , a ima i antiretroviralna svojstva u tretmanu bolesti kao što je AIDS .
Hidroksikarbamid umanjuje produkciju dezoksiribonukleotida [6] ribonukleotidna reduktaza tako što uklanja tirozilne slobodne radikale koji učestvuju u NDP redukciji.[7]
U lečenju srpaste anemije , hidroksikarbamid povišava koncentraciju fetusnog hemoglobina . Precizni mehanizam dejstva još uvek nije poznat, mada postoje indikacije da hidroksikarbamid povišava nivoe azot-monoksida , uzrokujući aktivaciju rastvorne guanilil ciklaze , što dovodi do povišenja nivoa cikličnog CMP , i aktivacije gamaglobinske sinteze neophodne za fetusni hemoglobin (uklanjanjem ćelija koje predominantno formiraju srpasti hemoglobin). Mali broj klonova crvenih krvnih zrnaca, poznatih kao F ćelije, su potomci male populacije nezrelih eritroidnih prekursora (BFU) koji zadržavaju sposobnost HbF produkcije.[7] [8]
↑ Li Q, Cheng T, Wang Y, Bryant SH (2010). "PubChem as a public resource for drug discovery." . Drug Discov Today 15 (23-24): 1052–7. PMID 20970519 . doi :10.1016/j.drudis.2010.10.003 . edit ↑ Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). "Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities". Annual Reports in Computational Chemistry 4 : 217–241. doi :10.1016/S1574-1400(08)00012-1 . ↑ Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). "Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining" . J Cheminform 2 (1): 3. PMID 20331846 . doi :10.1186/1758-2946-2-3 . edit ↑ Joanne Wixon, Douglas Kell (2000). "Website Review: The Kyoto Encyclopedia of Genes and Genomes — KEGG" . Yeast 17 (1): 48–55. doi :10.1002/(SICI)1097-0061(200004)17:1<48::AID-YEA2>3.0.CO;2-H . ↑ Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). "ChEMBL: a large-scale bioactivity database for drug discovery". Nucleic Acids Res 40 (Database issue): D1100–7. PMID 21948594 . doi :10.1093/nar/gkr777 . edit ↑ "hydroxyurea at Dorland's Medical Dictionary" . http://www.mercksource.com/pp/us/cns/cns_hl_dorlands_split.jsp?pg=/ppdocs/us/common/dorlands/dorland/four/000050608.htm . ↑ 7,0 7,1 Platt OS (2008). "Hydroxyurea for the treatment of sickle cell anemia". N. Engl. J. Med. 358 (13): 1362–9. PMID 18367739 . doi :10.1056/NEJMct0708272 . ↑ Cokic VP, Smith RD, Beleslin-Cokic BB et al. (2003). "Hydroxyurea induces fetal hemoglobin by the nitric oxide-dependent activation of soluble guanylyl cyclase" . J Clin Invest 111 (2): 231–9. PMC 151872 . PMID 12531879 . doi :10.1172/JCI16672 . ↑ Ghose, A.K., Viswanadhan V.N., and Wendoloski, J.J. (1998). "Prediction of Hydrophobic (Lipophilic) Properties of Small Organic Molecules Using Fragment Methods: An Analysis of AlogP and CLogP Methods" . J. Phys. Chem. A 102 : 3762–3772. doi :10.1021/jp980230o . ↑ Tetko IV, Tanchuk VY, Kasheva TN, Villa AE. (2001). "Estimation of Aqueous Solubility of Chemical Compounds Using E-State Indices" . Chem Inf. Comput. Sci. 41 : 1488–1493. PMID 11749573 . doi :10.1021/ci000392t . ↑ Ertl P., Rohde B., Selzer P. (2000). "Fast calculation of molecular polar surface area as a sum of fragment based contributions and its application to the prediction of drug transport properties" . J. Med. Chem. 43 : 3714–3717. PMID 11020286 . doi :10.1021/jm000942e .
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