Generic placeholder image

Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Research Article

A Computer - Aided Drug Designing for Pharmacological Inhibition of Mutant ALK for the Treatment of Non-small Cell Lung Cancer

Author(s): Saphy Sharda, Ravina Khandelwal, Ritu Adhikary, Diksha Sharma, Manisha Majhi, Tajamul Hussain, Anuraj Nayarisseri* and Sanjeev Kumar Singh*

Volume 19, Issue 13, 2019

Page: [1129 - 1144] Pages: 16

DOI: 10.2174/1568026619666190521084941

Price: $65


Background: Lung cancer is the most common among all the types of cancer worldwide with 1.8 million people diagnosed every year, leading to 1.6 million deaths every year according to the American cancer society. The involvement of mutated Anaplasic Lymphoma Kinase (ALK) positive fusion protein in the progression of NSCLC has made a propitious target to inhibit and treat NSCLC. In the present study, the main motif is to screen the most effective inhibitor against ALK protein with the potential pharmacological profile. The ligands selected were docked with Molegro Virtual Docker (MVD) and CEP-37440 (PubChem CID- 71721648) was the best docked pre-established compound with a permissible pharmacological profile.

Methods: The selected ligands were docked with Molegro Virtual Docker (MVD). With reference to the obtained compound with the lowest re-rank score, PubChem database was virtually screened to retrieve a large set of similar compounds which were docked to find the compound with higher affinity. Further comparative studies and in silico prediction included pharmacophore studies, proximity energy parameters, ADMET and BOILED-egg plot analysis.

Results: CEP-37440 (PubChem CID- 71721648) was the best docked pre-established compound with preferable pharmacological profile and PubChem compound CID-123449015 came out as the most efficient virtually screened inhibitor. Interestingly, the contours of the virtual screened compound PubChem CID- 123449015 fall within our desired high volume cavity of protein having admirable property to control the ALK regulation to prevent carcinogenesis in NSCLC. BOILED-Egg plot analysis depicts that both the compounds have analogous characteristics in the divergent aspects. Moreover, in the evaluations of Blood Brain Barrier, Human Intestinal Absorption, AMES toxicity, and LD50, the virtually screened compound (PubChem CID-123449015) was found within high optimization.

Conclusion: These investigations denote that the virtually screened compound (PubChem CID- 123449015) is more efficient to be a better prospective candidate for NSCLC treatment having good pharmacological profile than the pre-established compound CEP-37440 (PubChem CID- 71721648) with low re-rank score. The identified virtually screened compound has high potential to act as an ALK inhibitor and can show promising results in the research of non-small cell lung cancer (NSCLC).

Keywords: Non-small cell lung cancer (NSCLC), Anaplastic Lymphoma Kinase, ADMET, Molecular Docking, Virtual Screened, BOILED-Egg plot.

Graphical Abstract
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2016. CA Cancer J. Clin., 2016, 66(1), 7-30.
[] [PMID: 26742998]
Morris, S.W.; Kirstein, M.N.; Valentine, M.B.; Dittmer, K.G.; Shapiro, D.N.; Saltman, D.L.; Look, A.T. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science, 1994, 263(5151), 1281-1284.
[] [PMID: 8122112]
Morris, S.W.; Naeve, C.; Mathew, P.; James, P.L.; Kirstein, M.N.; Cui, X.; Witte, D.P. ALK, the chromosome 2 gene locus altered by the t(2;5) in non-Hodgkin’s lymphoma, encodes a novel neural receptor tyrosine kinase that is highly related to leukocyte tyrosine kinase (LTK). Oncogene, 1997, 14(18), 2175-2188.
[] [PMID: 9174053]
Yao, S.; Cheng, M.; Zhang, Q.; Wasik, M.; Kelsh, R.; Winkler, C. Anaplastic lymphoma kinase is required for neurogenesis in the developing central nervous system of zebrafish. PLoS One, 2013, 8(5)e63757
[] [PMID: 23667670]
Soda, M.; Takada, S.; Takeuchi, K.; Choi, Y.L.; Enomoto, M.; Ueno, T.; Haruta, H.; Hamada, T.; Yamashita, Y.; Ishikawa, Y.; Sugiyama, Y.; Mano, H. A mouse model for EML4-ALK-positive lung cancer. Proc. Natl. Acad. Sci. USA, 2008, 105(50), 19893-19897.
[] [PMID: 19064915]
Koivunen, J.P.; Mermel, C.; Zejnullahu, K.; Murphy, C.; Lifshits, E.; Holmes, A.J.; Choi, H.G.; Kim, J.; Chiang, D.; Thomas, R.; Lee, J.; Richards, W.G.; Sugarbaker, D.J.; Ducko, C.; Lindeman, N.; Marcoux, J.P.; Engelman, J.A.; Gray, N.S.; Lee, C.; Meyerson, M.; Jänne, P.A. EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin. Cancer Res., 2008, 14(13), 4275-4283.
[] [PMID: 18594010]
Lawrence, B.; Perez-Atayde, A.; Hibbard, M.K.; Rubin, B.P.; Dal Cin, P.; Pinkus, J.L.; Pinkus, G.S.; Xiao, S.; Yi, E.S.; Fletcher, C.D.; Fletcher, J.A. TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors. Am. J. Pathol., 2000, 157(2), 377-384.
[] [PMID: 10934142]
Lamant, L.; Gascoyne, R.D.; Duplantier, M.M.; Armstrong, F.; Raghab, A.; Chhanabhai, M.; Rajcan-Separovic, E.; Raghab, J.; Delsol, G.; Espinos, E. Non-muscle myosin heavy chain (MYH9): A new partner fused to ALK in anaplastic large cell lymphoma. Genes Chromosomes Cancer, 2003, 37(4), 427-432.
[] [PMID: 12800156]
Christensen, J.G.; Zou, H.Y.; Arango, M.E.; Li, Q.; Lee, J.H.; McDonnell, S.R.; Yamazaki, S.; Alton, G.R.; Mroczkowski, B.; Los, G. Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma. Mol. Cancer Ther., 2007, 6(12 Pt 1), 3314-3322.
[] [PMID: 18089725]
Antoniu, S.A. Crizotinib for EML4-ALK positive lung adenocarcinoma: a hope for the advanced disease? Evaluation of Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 2010;363(18):1693-703. Expert Opin. Ther. Targets, 2011, 15(3), 351-353.
[] [PMID: 21208134]
Kwak, E.L.; Bang, Y-J.; Camidge, D.R.; Shaw, A.T.; Solomon, B.; Maki, R.G.; Ou, S.H.; Dezube, B.J.; Jänne, P.A.; Costa, D.B.; Varella-Garcia, M.; Kim, W.H.; Lynch, T.J.; Fidias, P.; Stubbs, H.; Engelman, J.A.; Sequist, L.V.; Tan, W.; Gandhi, L.; Mino-Kenudson, M.; Wei, G.C.; Shreeve, S.M.; Ratain, M.J.; Settleman, J.; Christensen, J.G.; Haber, D.A.; Wilner, K.; Salgia, R.; Shapiro, G.I.; Clark, J.W.; Iafrate, A.J. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N. Engl. J. Med., 2010, 363(18), 1693-1703.
[] [PMID: 20979469]
Choi, Y.L.; Soda, M.; Yamashita, Y.; Ueno, T.; Takashima, J.; Nakajima, T.; Yatabe, Y.; Takeuchi, K.; Hamada, T.; Haruta, H.; Ishikawa, Y. EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N. Engl. J. Med., 2010, 363(18), 1734-1739.
[[DOI: 10.1056/NEJMoa1007478]
Sakamoto, H.; Tsukaguchi, T.; Hiroshima, S.; Kodama, T.; Kobayashi, T.; Fukami, T.A.; Oikawa, N.; Tsukuda, T.; Ishii, N.; Aoki, Y. CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell, 2011, 19(5), 679-690.
[] [PMID: 21575866]
Badalà, F.; Nouri-mahdavi, K.; Raoof, D.A. NIH Public Access. Computer (Long Beach Calif), 2008, 144(5), 724-732.
Amanam, I.; Gupta, R.; Mambetsariev, I.; Salgia, R. The brigatinib experience: A new generation of therapy for ALK-positive non-small-cell lung cancer. Future Oncol., 2018, 14(19), 1897-1908.
[] [PMID: 29451020]
Sullivan, I.; Planchard, D. ALK inhibitors in non-small cell lung cancer: the latest evidence and developments. Ther. Adv. Med. Oncol., 2016, 8(1), 32-47.
[] [PMID: 26753004]
Berghmans, T.; Remmelink, M.; Awada, A. Anaplastic lymphoma kinase (ALK) inhibitors for second-line therapy of non-small cell lung cancer. Lung Cancer (Auckl.), 2012, 3, 91-99.
[] [PMID: 28210128]
Drew, L.; Cheng, J.; Engelman, J.; Ferguson, D.; Katayama, R.; McDermott, B.; Wu, A. Abstract 919: AZD3463, a novel ALK/IGF1R inhibitor, overcomes multiple mechanisms of acquired resistance to crizotinib. 2013, 73(8 Suppl), 919.
Puig de la Bellacasa, R.; Karachaliou, N.; Estrada-Tejedor, R.; Teixidó, J.; Costa, C.; Borrell, J.I. ALK and ROS1 as a joint target for the treatment of lung cancer: a review. Transl. Lung Cancer Res., 2013, 2(2), 72-86.
[PMID: 25806218]
Ma, D.; Hao, X.; Wang, Y.; Xing, P.; Li, J. Clinical effect of pemetrexed as the first-line treatment in Chinese patients with advanced anaplastic lymphoma kinase-positive non-small cell lung cancer. Thorac. Cancer, 2016, 7(4), 452-458.
[] [PMID: 27385988]
Soda, M.; Choi, Y.L.; Enomoto, M.; Takada, S.; Yamashita, Y.; Ishikawa, S.; Fujiwara, S.; Watanabe, H.; Kurashina, K.; Hatanaka, H.; Bando, M.; Ohno, S.; Ishikawa, Y.; Aburatani, H.; Niki, T.; Sohara, Y.; Sugiyama, Y.; Mano, H. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature, 2007, 448(7153), 561-566.
[] [PMID: 17625570]
Kang, C.H.; Yun, J.I.; Lee, K.; Lee, C.O.; Lee, H.K.; Yun, C.S.; Hwang, J.Y.; Cho, S.Y.; Jung, H.; Kim, P.; Ha, J.D.; Jeon, J.H.; Choi, S.U.; Jeong, H.G.; Kim, H.R.; Park, C.H. Development of potent ALK inhibitor and its molecular inhibitory mechanism against NSCLC harboring EML4-ALK proteins. Biochem. Biophys. Res. Commun., 2015, 464(3), 762-767.
[] [PMID: 26168728]
Rossi, A.; Maione, P.; Sacco, P.C.; Sgambato, A.; Casaluce, F.; Ferrara, M.L.; Palazzolo, G.; Ciardiello, F.; Gridelli, C. ALK inhibitors and advanced non-small cell lung cancer.(review) Int. J. Oncol., 2014, 45(2), 499-508.
[ 10.3892/ijo.2014.2475] [PMID: 24889366]
Webb, T.R.; Slavish, J.; George, R.E.; Look, A.T.; Xue, L.; Jiang, Q.; Cui, X.; Rentrop, W.B.; Morris, S.W. Anaplastic lymphoma kinase: role in cancer pathogenesis and small-molecule inhibitor development for therapy. Expert Rev. Anticancer Ther., 2009, 9(3), 331-356.
[] [PMID: 19275511]
Solomon, B.J.; Mok, T.; Kim, D.W.; Wu, Y.L.; Nakagawa, K.; Mekhail, T.; Felip, E.; Cappuzzo, F.; Paolini, J.; Usari, T.; Iyer, S.; Reisman, A.; Wilner, K.D.; Tursi, J.; Blackhall, F. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N. Engl. J. Med., 2014, 371(23), 2167-2177.
[] [PMID: 25470694]
Borghaei, H.; Paz-Ares, L.; Horn, L.; Spigel, D.R.; Steins, M.; Ready, N.E.; Chow, L.Q.; Vokes, E.E.; Felip, E.; Holgado, E.; Barlesi, F.; Kohlhäufl, M.; Arrieta, O.; Burgio, M.A.; Fayette, J.; Lena, H.; Poddubskaya, E.; Gerber, D.E.; Gettinger, S.N.; Rudin, C.M.; Rizvi, N.; Crinò, L.; Blumenschein, G.R., Jr; Antonia, S.J.; Dorange, C.; Harbison, C.T.; Graf Finckenstein, F.; Brahmer, J.R. Nivolumab versus docetaxel in advanced nonsquamous non–small-cell lung cancer. N. Engl. J. Med., 2015, 373(17), 1627-1639.
[ ] [PMID: 26412456]
Ramamurthy, V.; Krystek, S.R., Jr; Bush, A.; Wei, A.; Emanuel, S.L.; Das Gupta, R.; Janjua, A.; Cheng, L.; Murdock, M.; Abramczyk, B.; Cohen, D.; Lin, Z.; Morin, P.; Davis, J.H.; Dabritz, M.; McLaughlin, D.C.; Russo, K.A.; Chao, G.; Wright, M.C.; Jenny, V.A.; Engle, L.J.; Furfine, E.; Sheriff, S. Structures of adnectin/protein complexes reveal an expanded binding footprint. Structure, 2012, 20(2), 259-269.
[] [PMID: 22325775]
Bandaru, S.; Sumithnath, T.G.; Sharda, S.; Lakhotia, S.; Sharma, A.; Jain, A.; Hussain, T.; Nayarisseri, A.; Singh, S.K. Helix-coil transition signatures B-Raf V600E mutation and virtual screening for inhibitors directed against mutant B-Raf. Curr. Drug Metab., 2017, 18(6), 527-534.
[ ] [PMID: 28472910]
Nasr, A.B.; Ponnala, D.; Sagurthi, S.R.; Kattamuri, R.K.; Marri, V.K.; Gudala, S.; Lakkaraju, C.; Bandaru, S.; Nayarisseri, A. Molecular docking studies of FKBP12-mTOR inhibitors using binding predictions. Bioinformation, 2015, 11(6), 307-315.
[] [PMID: 26229292]
Cheng, F.; Li, W.; Zhou, Y.; Shen, J.; Wu, Z.; Liu, G.; Lee, P.W.; Tang, Y. admetSAR: A comprehensive source and free tool for assessment of chemical ADMET properties. J. Chem. Inf. Model., 2012, 52(11), 3099-3105.
Dunna, N.R.; Kandula, V.; Girdhar, A.; Pudutha, A.; Hussain, T.; Bandaru, S.; Nayarisseri, A. High affinity pharmacological profiling of dual inhibitors targeting RET and VEGFR2 in inhibition of kinase and angiogeneis events in medullary thyroid carcinoma. Asian Pac. J. Cancer Prev., 2015, 16(16), 7089-7095.
[ ] [PMID: 26514495]
Sinha, C.; Nischal, A.; Bandaru, S.; Kasera, P.; Rajput, A.; Nayarisseri, A.; Khattri, S. An in silico approach for identification of novel inhibitors as a potential therapeutics targeting HIV-1 viral infectivity factor. Curr. Top. Med. Chem., 2015, 15(1), 65-72.
[ ] [PMID: 25579575]
Sinha, C.; Nischal, A.; Pant, K.K.; Bandaru, S.; Nayarisseri, A.; Khattri, S. Molecular docking analysis of RN18 and VEC5 in A3G-Vif inhibition. Bioinformation, 2014, 10(10), 611-616.
[] [PMID: 25489169]
Bandaru, S.; Marri, V.K.; Kasera, P.; Kovuri, P.; Girdhar, A.; Mittal, D.R.; Ikram, S.; Gv, R.; Nayarisseri, A. Structure based virtual screening of ligands to identify cysteinyl leukotriene receptor 1 antagonist. Bioinformation, 2014, 10(10), 652-657.
[] [PMID: 25489175]
Dunna, N.R.; Bandaru, S.; Akare, U.R.; Rajadhyax, S.; Gutlapalli, V.R.; Yadav, M.; Nayarisseri, A. Multiclass comparative virtual screening to identify novel Hsp90 inhibitors: a therapeutic breast cancer drug target. Curr. Top. Med. Chem., 2015, 15(1), 57-64.
[ ] [PMID: 25579569]
Bandaru, S.; Ponnala, D.; Lakkaraju, C.; Bhukya, C.K.; Shaheen, U.; Nayarisseri, A. Identification of high affinity non-peptidic small molecule inhibitors of MDM2-p53 interactions through structure-based virtual screening strategies. Asian Pac. J. Cancer Prev., 2015, 16(9), 3759-3765.
[ ] [PMID: 25987034]
Akare, U.R.; Bandaru, S.; Shaheen, U.; Singh, P.K.; Tiwari, G.; Singare, P.; Nayarisseri, A.; Banerjee, T. Molecular docking approaches in identification of High affinity inhibitors of Human SMO receptor. Bioinformation, 2014, 10(12), 737-742.
[] [PMID: 25670876]
Bandaru, S.; Alvala, M.; Akka, J.; Sagurthi, S.R.; Nayarisseri, A.; Singh, S.K.; Mundluru, H.P. Identification of small molecule as a high affinity β2 agonist promiscuously targeting wild and mutated (Thr164Ile) β 2 adrenergic receptor in the treatment of bronchial asthma. Curr. Pharm. Des., 2016, 22(34), 5221-5233.
[ ] [PMID: 27174812]
Bandaru, S.; Prasad, M.H.; Jyothy, A.; Nayarisseri, A.; Yadav, M. Binding modes and pharmacophoric features of muscarinic antagonism and β2 agonism (MABA) conjugates. Curr. Top. Med. Chem., 2013, 13(14), 1650-1655.
[ ] [PMID: 23889054]
Nayarisseri, A.; Moghni, S.M.; Yadav, M.; Kharate, J.; Sharma, P.; Chandok, K.H.; Shah, K.P. In silico investigations on HSP90 and its inhibition for the therapeutic prevention of breast cancer. J. Pharm. Res., 2013, 7(2), 150-156.
Shaheen, U.; Akka, J.; Hinore, J.S.; Girdhar, A.; Bandaru, S.; Sumithnath, T.G.; Nayarisseri, A.; Munshi, A. Computer aided identification of sodium channel blockers in the clinical treatment of epilepsy using molecular docking tools. Bioinformation, 2015, 11(3), 131-137.
[] [PMID: 25914447]
Vuree, S.; Dunna, N.R.; Khan, I.A.; Alharbi, K.K.; Vishnupriya, S.; Soni, D.; Shah, P.; Chandok, H.; Yadav, M.; Nayarisseri, A. Pharmacogenomics of drug resistance in breast cancer resistance protein (BCRP) and its mutated variants. J. Pharm. Res., 2013, 6(7), 791-798.
Gudala, S.; Khan, U.; Kanungo, N.; Bandaru, S.; Hussain, T.; Parihar, M.; Nayarisseri, A.; Mundluru, H.P. Identification and pharmacological analysis of high efficacy small molecule inhibitors of EGF-EGFR interactions in clinical treatment of non-small cell lung carcinoma: A computational approach. Asian Pac. J. Cancer Prev., 2015, 16(18), 8191-8196.
[] [PMID: 26745059]
Babitha, P.P.; Sahila, M.M.; Bandaru, S.; Nayarisseri, A.; Sureshkumar, S. Molecular docking and pharmacological investigations of rivastigmine-fluoxetine and coumarin-tacrine hybrids against acetyl choline esterase. Bioinformation, 2015, 11(8), 378-386.
[] [PMID: 26420918]
Natchimuthu, V.; Bandaru, S.; Nayarisseri, A.; Ravi, S. Design, synthesis and computational evaluation of a novel intermediate salt of N-cyclohexyl-N-(cyclohexylcarbamoyl)-4-(trifluoromethyl) ben-zamide as potential potassium channel blocker in epileptic paroxysmal seizures. Comput. Biol. Chem., 2016, 64, 64-73.
[] [PMID: 27266485]
Patidar, K.; Deshmukh, A.; Bandaru, S.; Lakkaraju, C.; Girdhar, A.; Vr, G.; Banerjee, T.; Nayarisseri, A.; Singh, S.K. Virtual screening approaches in identification of bioactive compounds Akin to Delphinidin as potential HER2 inhibitors for the treatment of breast cancer. Asian Pac. J. Cancer Prev., 2016, 17(4), 2291-2295.
[] [PMID: 27221932]
Sahila, M.M.; Babitha, P.P.; Bandaru, S.; Nayarisseri, A.; Doss, V.A. Molecular docking based screening of GABA (A) receptor inhibitors from plant derivatives. Bioinformation, 2015, 11(6), 280-289.
[] [PMID: 26229288]
Bandaru, S.; Tarigopula, P.; Akka, J.; Marri, V.K.; Kattamuri, R.K.; Nayarisseri, A.; Mangalarapu, M.; Vinukonda, S.; Mundluru, H.P.; Sagurthi, S.R. Association of Beta 2 adrenergic receptor (Thr164Ile) polymorphism with Salbutamol refractoriness in severe asthmatics from Indian population. Gene, 2016, 592(1), 15-22.
[ ] [PMID: 27450915]
Khandekar, N.; Singh, S.; Shukla, R.; Tirumalaraju, S.; Bandaru, S.; Banerjee, T.; Nayarisseri, A. Structural basis for the in vitro known acyl-depsipeptide 2 (ADEP2) inhibition to Clp 2 protease from Mycobacterium tuberculosis. Bioinformation, 2016, 12(3), 92-97.
[] [PMID: 28149041]
Bandaru, S.; Alvala, M.; Nayarisseri, A.; Sharda, S.; Goud, H.; Mundluru, H.P.; Singh, S.K. Molecular dynamic simulations reveal suboptimal binding of salbutamol in T164I variant of β2 adrenergic receptor. PLoS One, 2017, 12(10)e0186666
[] [PMID: 29053759]
Sharda, S.; Sarmandal, P.; Cherukommu, S.; Dindhoria, K.; Yadav, M.; Bandaru, S.; Sharma, A.; Sakhi, A.; Vyas, T.; Hussain, T.; Nayarisseri, A.; Singh, S.K. A virtual screening approach for the identification of high affinity small molecules targeting BCR-ABL1 inhibitors for the treatment of chronic myeloid leukemia. Curr. Top. Med. Chem., 2017, 17(26), 2989-2996.
[] [PMID: 28828991]
Jain, D.; Udhwani, T.; Sharma, S.; Gandhe, A.; Reddy, P.B.; Nayarisseri, A.; Singh, S.K. Design of novel JAK3 Inhibitors towards Rheumatoid Arthritis using molecular docking analysis. Bioinformation, 2019, 15(2), 68-78.
Monteiro, A.F.M.; Viana, J.O.; Nayarisseri, A.; Zondegoumba, E.N.; Mendonça, Junior, F.J.B.; Scotti, M.T.; Scotti, L. Computational studies applied to flavonoids against alzheimer’s and parkinson’s diseases. Oxid. Med. Cell. Longev., 2018, 2018, 21.
[] [PMID: 30693065]
Nayarisseri, A.; Hood, E.A. Advancement in microbial cheminformatics. Curr. Top. Med. Chem., 2018, 18(29), 2459-2461.
[] [PMID: 30457050]
Gokhale, P. Chauhan. A.P.S.; Arora, A.; Khandekar, N.; Nayarisseri, A.; Singh, S.K. FLT3 inhibitor design using molecular docking based virtual screening for acute myeloid leukemia. Bioinformation, 2019, 15(2), 104-115.
Shukla, P.; Khandelwal, R.; Sharma, D.; Dhar, A.; Nayarisseri, A.; Singh, S.K. Virtual Screening of IL-6 Inhibitors for Idiopathic Arthritis. Bioinformation, 2019, 15(2), 121-130.
Udhwani, T.; Mukherjee, S.; Sharma, K. Sweta, J; Khandekar, N.; Nayarisseri, A.; Singh, S.K. Design of PD-L1 inhibitors for lung cancer. Bioinformation, 2019, 15(2), 139-150.
Rao, D.M.; Nayarisseri, A.; Yadav, M.; Patel, D. Comparative modeling of methylentetrahydrofolate reductase (MTHFR) enzyme and its mutational assessment: in silico approach. Int. J. Bioinformat. Res., 2010, 2(1), 5-9.
Kelotra, S.; Jain, M.; Kelotra, A.; Jain, I.; Bandaru, S.; Nayarisseri, A.; Bidwai, A. An in silico appraisal to identify high affinity anti-apoptotic synthetic tetrapeptide inhibitors targeting the mammalian caspase 3 enzyme. Asian Pac. J. Cancer Prev., 2014, 15(23), 10137-10142.
[ ] [PMID: 25556438]
Gutlapalli, V.R.; Sykam, A.; Nayarisseri, A.; Suneetha, S.; Suneetha, L.M. Insights from the predicted epitope similarity between Mycobacterium tuberculosis virulent factors and its human homologs. Bioinformation, 2015, 11(12), 517-524.
[] [PMID: 26770024]
Nayarisseri, A.; Yadav, M.; Wishard, R. Computational evaluation of new homologous down regulators of Translationally Controlled Tumor Protein (TCTP) targeted for tumor reversion. Interdiscip. Sci., 2013, 5(4), 274-279.
[] [PMID: 24402820]
Praseetha, S.; Bandaru, S.; Nayarisseri, A.; Sureshkumar, S. Pharmacological analysis of vorinostat analogues as potential anti-tumor agents targeting human histone deacetylases: An epigenetic treatment stratagem for cancers. Asian Pac. J. Cancer Prev., 2016, 17(3), 1571-1576.
[] [PMID: 27039807]
Majhi, M.; Ali, M.A.; Limaye, A.; Sinha, K.; Bairagi, P.; Chouksey, M.; Shukla, R.; Kanwar, N.; Hussain, T.; Nayarisseri, A.; Singh, S.K. An in silico investigation of potential EGFR inhibitors for the clinical treatment of colorectal cancer. Curr. Top. Med. Chem., 2018, 18(27), 2355-2366.
[] [PMID: 30499396]
Sharma, K.; Patidar, K.; Ali, M.A.; Patil, P.; Goud, H.; Hussain, T.; Nayarisseri, A.; Singh, S.K. Structure-based virtual screening for the identification of high affinity compounds as potent VEGFR2 inhibitors for the treatment of renal cell carcinoma. Curr. Top. Med. Chem., 2018, 18(25), 2174-2185.
[] [PMID: 30499413]
Shameer, K.; Nayarisseri, A.; Romero Duran, F.X.; González-Díaz, H. Improving neuropharmacology using big data, machine learning and computational algorithms. Curr. Neuropharmacol., 2017, 15(8), 1058-1061.
[] [PMID: 29199918]
Basak, S.C.; Nayarisseri, A.; González-Díaz, H.; Bonchev, D. Editorial (Thematic Issue: Chemoinformatics models for pharmaceutical design, Part 2). Curr. Pharm. Des., 2016, 22(34), 5177-5178.
[] [PMID: 27852211]
Basak, S.C.; Nayarisseri, A.; González-Díaz, H.; Bonchev, D. Editorial (Thematic Issue: Chemoinformatics models for pharmaceutical design, Part 1). Curr. Pharm. Des., 2016, 22(33), 5041-5042.
[] [PMID: 27852204]
Kelotra, A.; Gokhale, S.M.; Kelotra, S.; Mukadam, V.; Nagwanshi, K.; Bandaru, S.; Nayarisseri, A.; Bidwai, A. Alkyloxy carbonyl modified hexapeptides as a high affinity compounds for Wnt5A protein in the treatment of psoriasis. Bioinformation, 2014, 10(12), 743-749.
[] [PMID: 25670877]
Sinha, K.; Majhi, M.; Thakur, G.; Patidar, K.; Sweta, J.; Hussain, T.; Nayarisseri, A.; Singh, S.K. Computer aided drug designing for the identification of high affinity small molecule targeting CD20 for the clinical treatment of Chronic Lymphocytic Leukemia (CLL). Curr. Top. Med. Chem., 2018, 18(29), 2527-2542.
[] [PMID: 30526461]
Chandrakar, B.; Jain, A.; Roy, S.; Gutlapalli, V.R.; Saraf, S.; Suppahia, A.; Verma, A.; Tiwari, A.; Yadav, M.; Nayarisseri, A. Molecular modeling of Acetyl-CoA carboxylase (ACC) from Jatropha curcas and virtual screening for identification of inhibitors. J. Pharm. Res., 2013, 6(9), 913-918.
Khandelwal, R.; Chauhan, A.P.S.; Bilawat, S.; Gandhe, A.; Hussain, T.; Hood, E.A.; Nayarisseri, A.; Singh, S.K. Structure-based virtual screening for the identification of high affinity small molecule towards STAT3 for the clinical treatment of Osteosarcoma. Curr. Top. Med. Chem., 2018, 18(29), 2511-2526.
[] [PMID: 30430945]
Singh, S.K.; Nayarisseri, A. Functional inhibition of VEGF and EGFR suppressors in cancer treatment. Curr. Top. Med. Chem., 2019, 19(3), 178-179.
[] [PMID: 30950335]
Monteiro, A.F.M.; Viana, J.O.; Nayarisseri, A.; Zondegoumba, E.N.; Mendonça, Junior, F.J.B.; Scotti, M.T.; Scotti, L. Computational studies applied to flavonoids against alzheimer’s and parkinson’s diseases. Oxid. Med. Cell. Longev., 2018, 20187912765
[ ] [PMID: 30693065]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy