Drug formulation studies on regulation of BCL-2 family for treatment of autism
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POSTER PRESENTATION Open Access Drug formulation studies on regulation of BCL-2 family for treatment of autism Iftikhar A Tayubi 1,3* , Sayane Shome 2 , Sarosh Hashmi 3 From 2nd International Genomic Medical Conference (IGMC 2013) Jeddah, Kingdom of Saudi Arabia. 24-27 November 2013 Background BCL2 and Bax are two members of BCL2 family which is responsible for the regulation of apotosis [1,2]. BCL2 pro- tein duels with its counteracting twin, a partner known as Bax (Figure 1). When Bax is in excess, cells execute a death command. When BCL2 dominates, the program is inhibited and cells survive. The intent is to propose a drug complex which aids in regulation of the BCL2 and Bax levels, aiding in treatment of autism. Navitoclax is known drug responsible for inhibiting BCL2 production for the treatment of cancer. We suggest a drug formulation of navitoclax with a Bax channel locker. Materials and methods The structures of Navitoclax (Pubchem ID : 923564-51-6) and Bax channel locker (Pubchem ID :335165-68-9) were taken from Pubchem database. Their binding affinity and energies with target components were analysed using Autodock 4.0.The active site residues in the target proteins BCL2 (Figure 2) and BAX were determined by literature studies and using CastP and Sp align software. The admet properties and pharmacological properties of the drug were calculated using Discovery studio software. Results Based on the binding affinities of Navitoclax and Bax Channel Locker with its respective target proteins BCL2 and Bax respectively, the target functional groups to con- nect the two ligands were shortlisted. It was taken care the responsible target binding sites aren’t affected with the linkage. Four combinations (Figure 3) were created. Their pharmacological properties were predicted insilico to * Correspondence: [email protected] 1 Faculty of Computing and Information Technology, King Abdulaziz University, Rabigh-21911, Saudi Arabia Full list of author information is available at the end of the article Figure 1 (Left): Regulation of apoptosis pathway by family of BCL-2 proteins Figure 2 (Top right): BCL-2 protein docked with Navitoclax [PDB Id: 4LXE] Tayubi et al. BMC Genomics 2014, 15(Suppl 2):P38 http://www.biomedcentral.com/1471-2164/15/S2/P38 © 2014 Tayubi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transcript of Drug formulation studies on regulation of BCL-2 family for treatment of autism
POSTER PRESENTATION Open Access
Drug formulation studies on regulation of BCL-2family for treatment of autismIftikhar A Tayubi1,3*, Sayane Shome2, Sarosh Hashmi3
From 2nd International Genomic Medical Conference (IGMC 2013)Jeddah, Kingdom of Saudi Arabia. 24-27 November 2013
BackgroundBCL2 and Bax are two members of BCL2 family which isresponsible for the regulation of apotosis [1,2]. BCL2 pro-tein duels with its counteracting twin, a partner known asBax (Figure 1). When Bax is in excess, cells execute adeath command. When BCL2 dominates, the program isinhibited and cells survive. The intent is to propose a drugcomplex which aids in regulation of the BCL2 and Baxlevels, aiding in treatment of autism. Navitoclax is knowndrug responsible for inhibiting BCL2 production for thetreatment of cancer. We suggest a drug formulation ofnavitoclax with a Bax channel locker.
Materials and methodsThe structures of Navitoclax (Pubchem ID : 923564-51-6)and Bax channel locker (Pubchem ID :335165-68-9) weretaken from Pubchem database. Their binding affinity andenergies with target components were analysed usingAutodock 4.0.The active site residues in the target proteinsBCL2 (Figure 2) and BAX were determined by literaturestudies and using CastP and Sp align software. The admetproperties and pharmacological properties of the drugwere calculated using Discovery studio software.
ResultsBased on the binding affinities of Navitoclax and BaxChannel Locker with its respective target proteins BCL2and Bax respectively, the target functional groups to con-nect the two ligands were shortlisted. It was taken care theresponsible target binding sites aren’t affected with thelinkage. Four combinations (Figure 3) were created. Theirpharmacological properties were predicted insilico to
* Correspondence: [email protected] of Computing and Information Technology, King AbdulazizUniversity, Rabigh-21911, Saudi ArabiaFull list of author information is available at the end of the article
Figure 1 (Left): Regulation of apoptosis pathway by family of BCL-2proteins
Figure 2 (Top right): BCL-2 protein docked with Navitoclax [PDBId: 4LXE]
Tayubi et al. BMC Genomics 2014, 15(Suppl 2):P38http://www.biomedcentral.com/1471-2164/15/S2/P38
© 2014 Tayubi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.
shortlist the best combination. The predicted propertiesinferred the drug complex to be non-carcinogenic, andnon-mutagen and may display moderate irritancy. Thenovel drug complex can be further modified and analyzedto get drug with lower molecular weight and displayinglow to no irritancy.
ConclusionsThe admet and chemical properties suggest there are pos-sibilities to consider the new drug complex designed forfurther analysis.
Authors’ details1Faculty of Computing and Information Technology, King AbdulazizUniversity, Rabigh-21911, Saudi Arabia. 2School of Biosciences andTechnology, Vellore Institute of Technology, Vellore-632014, India. 3Faculty ofComputing and Information Technology, King Abdulaziz University, Rabigh-21911, Saudi Arabia.
Published: 2 April 2014
References1. Belka C, Budach W: Anti-apoptotic Bcl-2 proteins: structure, function and
relevance for radiation biology. Int J Radiat Biol 2002, 78(8):643-58.2. Helen V, Ratajczak : Theoretical aspects of autism: Causes. A review.
Journal of Immunotoxicology 2011, 8(1):68-79.
doi:10.1186/1471-2164-15-S2-P38Cite this article as: Tayubi et al.: Drug formulation studies on regulationof BCL-2 family for treatment of autism. BMC Genomics 2014 15(Suppl 2):P38.
Figure 3 (Bottom right): Chemical structure of the novel designed drug complex
Tayubi et al. BMC Genomics 2014, 15(Suppl 2):P38http://www.biomedcentral.com/1471-2164/15/S2/P38
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