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Discovering novel carbonic anhydrase type IX (CA IX) inhibitors from seven million compounds using virtual screening and in vitro analysis.
J Enzyme Inhib Med Chem. 2016; 31(3):425-33.JE

Abstract

Carbonic anhydrase type IX (CA IX) enzyme is mostly over expressed in different cancer cell lines and tumor tissues. Potent CA IX inhibitors can be effective for adjusting the pH imbalance in tumor cells. In the present work, we represented the successful application of high throughput virtual screening (HTVS) of large dataset from ZINC database included of ∼7 million compounds to discover novel inhibitors of CA IX. HTVS and molecular docking were performed using consequence Glide/standard precision (SP), extra precision (XP) and induced fit docking (IFD) molecular docking protocols. For each compound, docking code calculates a set of low-energy poses and then exhaustively scans the binding pocket of the target with small compounds. Novel CA IX inhibitor candidates were suggested based on molecular modeling studies and a few of them were tested using in vitro analysis. These compounds were determined as good inhibitors against human CA IX target with Ki in the range of 0.85-1.58 μM. In order to predict the pharmaceutical properties of the selected compounds, ADME (absorption, distribution, metabolism and excretion) analysis was also carried out.

Authors+Show Affiliations

a Department of Chemistry , İstanbul Technical University , İstanbul , Turkey .b Department of Chemistry , Ağrı Ibrahim Çeçen University , Ağrı , Turkey , and.a Department of Chemistry , İstanbul Technical University , İstanbul , Turkey .c Department of Biophysics , School of Medicine, Bahçeşehir University , Istanbul , Turkey.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25950196

Citation

Salmas, Ramin Ekhteiari, et al. "Discovering Novel Carbonic Anhydrase Type IX (CA IX) Inhibitors From Seven Million Compounds Using Virtual Screening and in Vitro Analysis." Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 31, no. 3, 2016, pp. 425-33.
Salmas RE, Senturk M, Yurtsever M, et al. Discovering novel carbonic anhydrase type IX (CA IX) inhibitors from seven million compounds using virtual screening and in vitro analysis. J Enzyme Inhib Med Chem. 2016;31(3):425-33.
Salmas, R. E., Senturk, M., Yurtsever, M., & Durdagi, S. (2016). Discovering novel carbonic anhydrase type IX (CA IX) inhibitors from seven million compounds using virtual screening and in vitro analysis. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(3), 425-33. https://doi.org/10.3109/14756366.2015.1036049
Salmas RE, et al. Discovering Novel Carbonic Anhydrase Type IX (CA IX) Inhibitors From Seven Million Compounds Using Virtual Screening and in Vitro Analysis. J Enzyme Inhib Med Chem. 2016;31(3):425-33. PubMed PMID: 25950196.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discovering novel carbonic anhydrase type IX (CA IX) inhibitors from seven million compounds using virtual screening and in vitro analysis. AU - Salmas,Ramin Ekhteiari, AU - Senturk,Murat, AU - Yurtsever,Mine, AU - Durdagi,Serdar, Y1 - 2015/05/07/ PY - 2015/5/8/entrez PY - 2015/5/8/pubmed PY - 2016/11/5/medline KW - ADME KW - CA IX inhibitors KW - carbonic anhydrase KW - molecular docking KW - virtual screening SP - 425 EP - 33 JF - Journal of enzyme inhibition and medicinal chemistry JO - J Enzyme Inhib Med Chem VL - 31 IS - 3 N2 - Carbonic anhydrase type IX (CA IX) enzyme is mostly over expressed in different cancer cell lines and tumor tissues. Potent CA IX inhibitors can be effective for adjusting the pH imbalance in tumor cells. In the present work, we represented the successful application of high throughput virtual screening (HTVS) of large dataset from ZINC database included of ∼7 million compounds to discover novel inhibitors of CA IX. HTVS and molecular docking were performed using consequence Glide/standard precision (SP), extra precision (XP) and induced fit docking (IFD) molecular docking protocols. For each compound, docking code calculates a set of low-energy poses and then exhaustively scans the binding pocket of the target with small compounds. Novel CA IX inhibitor candidates were suggested based on molecular modeling studies and a few of them were tested using in vitro analysis. These compounds were determined as good inhibitors against human CA IX target with Ki in the range of 0.85-1.58 μM. In order to predict the pharmaceutical properties of the selected compounds, ADME (absorption, distribution, metabolism and excretion) analysis was also carried out. SN - 1475-6374 UR - https://www.unboundmedicine.com/medline/citation/25950196/Discovering_novel_carbonic_anhydrase_type_IX__CA_IX__inhibitors_from_seven_million_compounds_using_virtual_screening_and_in_vitro_analysis_ L2 - http://www.tandfonline.com/doi/full/10.3109/14756366.2015.1036049 DB - PRIME DP - Unbound Medicine ER -