Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Review Article

Turning to Computer-aided Drug Design in the Treatment of Diffuse Large B-cell Lymphoma: Has it been Helpful?

Author(s): Aimen K. Aljoundi, Clement Agoni, Fisayo A. Olotu and Mahmoud E.S. Soliman*

Volume 19, Issue 11, 2019

Page: [1325 - 1339] Pages: 15

DOI: 10.2174/1871520619666190405111526

Price: $65

Abstract

Introduction: Amidst the numerous effective therapeutic options available for the treatment of Diffuse Large B-cell Lymphoma (DLBCL), about 30-40% of patients treated with first-line chemoimmunotherapy still experience a relapse or refractory DLBCL. This has necessitated a continuous search for new therapeutic agents to augment the existing therapeutic arsenal.

Methods: The dawn of Computer-Aided Drug Design (CADD) in the drug discovery process has accounted for persistency in the application of computational approaches either alone or in combinatorial strategies with experimental methods towards the identification of potential hit compounds with high therapeutic efficacy in abrogating DLBCL.

Results: This review showcases the interventions of structure-based and ligand-based computational approaches which have led to the identification of numerous small molecule inhibitors against implicated targets in DLBCL therapy, even though many of these potential inhibitors are piled-up awaiting further experimental validation and exploration.

Conclusion: We conclude that a successful and a conscious amalgamation of CADD and experimental approaches could pave the way for the discovery of the next generation potential leads in DLBCL therapy with improved activities and minimal toxicities.

Keywords: Diffuse large B-cell lymphoma, computer-aided drug design, small molecule inhibitors, CADD interventions, henry rappaport classification system, lymphoma.

Graphical Abstract
[1]
Lenz, G.; Staudt, L. Aggressive lymphomas. N. Engl. J. Med., 2010, 362(15), 1417-1429.
[2]
Staudt, L.; Dave, S. The biology of human lymphoid malignancies revealed by gene expression profiling. Adv. Immunol., 2005, 87, 163-208.
[3]
Coiffier, B.; Thieblemont, C.; Van Den Neste, E.; Lepeu, G.; Plantier, I.; Castaigne, S. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: A study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood, 2010, 116(12), 2040-2045.
[4]
Rappaport, H. Tumors of the Hematopoeitic System; Armed Forces Institute of Pathology: Washington, DC, 1996.
[5]
Li, S.; Young, K.H.; Medeiros, L.J. Diffuse large B-cell lymphoma. Pathology, 2018, 50(1), 74-87.
[6]
Korkolopoulou, P.; Vassilakopoulos, T.; Milionis, V.; Ioannou, M. Recent advances in aggressive large B-cell lymphomas: A comprehensive review. Adv. Anat. Pathol., 2016, 23, 202-243.
[7]
Swerdlow, S.H.; Campo, E.; Pileri, S.A.; Harris, N.L.; Stein, H.; Siebert, R.; Advani, R.; Ghielmini, M.; Salles, G.A.; Zelenetz, A.D.; Jaffe, E.S. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood, 2016, 127, 2375-2390.
[8]
Battistello, E.; Katanayeva, N.; Dheilly, E.; Tavernari, D.; Donaldson, M.C.; Bonsignore, L.; Thome, M.; Christie, A.L.; Murakami, M.A.; Michielin, O.; Ciriello, G.; Zoete, V.; Oricchio, E. Pan-SRC kinase inhibition blocks B-cell receptor oncogenic signaling in non-Hodgkin lymphoma. Blood, 2018, 131(21), 2345-2356.
[9]
Pasqualucci, L.; Trifonov, V.; Fabbri, G. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat. Genet., 2011, 43(9), 830-837.
[10]
Reddy, A.; Zhang, J.; Davis, N.S.; Ma, J.; Rossi, D.; Chiarenza, A.; Wells, V.A.; Grunn, A.; Messina, M.; Elliot, O.; Chan, J.; Bhagat, G.; Chadburn, A.; Gaidano, G.; Mullighan, C.G.; Rabadan, R.; Dalla-Favera, R. Genetic and functional drivers of diffuse large B cell lymphoma. Cell, 2017, 171(2), 481-494.
[11]
Alizadeh, A.; Eisen, M.; Davis, R.; Ma, C. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature, 2000, 403(6769), 503-511.
[12]
Rosenwald, A.; Wright, G.; Chan, W. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N. Engl. J. Med 346., 2002, 1937-1947.
[13]
Hans, C.P.; Weisenburger, D.D.; Greiner, T.C.; Gascoyne, R.D.; Delabie, J.; Ott, G.; Müller-Hermelink, H.K.; Campo, E.; Braziel, R.M.; Jaffe, E.S.; Pan, Z.; Farinha, P.; Smith, L.M.; Falini, B.; Banham, A.H.; Rosenwald, A.; Staudt, L.M.; Connors, J.M.; Armitage, J.O.; Chan, W.C. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood, 2004, 103(1), 275-282.
[14]
Compagno, M.; Lim, W.K.; Grunn, A.; Nandula, S.V.; Brahmachary, M.; Shen, Q.; Bertoni, F.; Ponzoni, M.; Scandurra, M.; Califano, A.; Bhagat, G.; Chadburn, A.; Dalla-Favera, R.; Pasqualucci, L. Mutations of multiple genes cause deregulation of NF-kB in diffuse large B-cell lymphoma. Nature, 2009, 459(7247), 717-721.
[15]
Davis, R.E.; Ngo, V.N.; Lenz, G.; Tolar, P.; Young, R.M.; Romesser, P.B.; Kohlhammer, H.; Lamy, L.; Zhao, H.; Yang, Y.; Xu, W.; Shaffer, A.L.; Wright, G.; Xiao, W.; Powell, J.; Jiang, J.K.; Thomas, C.J.; Rosenwald, A.; Ott, G.; Muller-Hermelink, H.K.; Gascoyne, R.D.; Connors, J.M.; Johnson, N.A.; Rimsza, L.M.; Campo, E.; Jaffe, E.S.; Wilson, W.H.; Delabie, J.; Smeland, E.B.; Fisher, R.I.; Braziel, R.M.; Tubbs, R.R.; Cook, J.R.; Weisenburger, D.D.; Chan, W.C.; Pierce, S.K.; Staudt, L.M. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature, 2010, 463(7277), 88-92.
[16]
Lenz, G.; Davis, R.E.; Ngo, V.N.; Lam, L.; George, T.C.; Wright, G.W.; Dave, S.S.; Zhao, H.; Xu, W.; Rosenwald, A.; Ott, G.; Muller-Hermelink, H.K.; Gascoyne, R.D.; Connors, J.M.; Rimsza, L.M.; Campo, E.; Jaffe, E.S.; Delabie, J.; Smeland, E.B.; Fisher, R.I.; Chan, W.C.; Staudt, L.M. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science, 2008, 319(5870), 1676-1679.
[17]
Lunning, M.; Green, M. The GCB subtype of DLBCL shows several chromosomal modifications including mutations in epigenetic modifiers and also exhibits an enhanced ectopic expression of the BCL2 protein. Blood Cancer J., 2015, 5(10)e361
[18]
Basso, K.; Dalla-Favera, R. Germinal centres and B cell lymphomagenesis. Nat. Rev. Immunol., 2015, 15(3), 172-184.
[19]
Morin, R.; Mendez-Lago, M.; Mungall, A. Frequent mutation of histonemodifying genes in non-Hodgkin lymphoma. Nature, 2011, 476(7360), 298-303.
[20]
Ngo, V.; Young, R.; Schmitz, R. Oncogenically active MYD88 mutations in human lymphoma. Nature, 2011, 470(7332), 115-119.
[21]
Martelli, M.; Ferreri, A.J.; Agostinelli, C.; Di Rocco, A.; Pfreundschuh, M.; Pileri, S.A. Diffuse large B-cell lymphoma. Crit. Rev. Oncol. Hematol., 2013, 87(2), 146-171.
[22]
Giulino-Roth, L. How I treat primary mediastinal B-cell lymphoma. Blood, 2018, 132(8), 782-790.
[23]
Lenz, G.; Wright, G.; Dave, S.; Xiao, W.; Powell, J.; Zhao, H. Stromal gene signatures in large-B-cell lymphomas. N. Engl. J. Med., 2008, 359, 2313-2323.
[24]
Dunleavy, K.; Roschewski, M.; Wilson, W. Precision treatment of distinct molecular subtypes of diffuse large B-cell lymphoma: ascribing treatment based on the molecular phenotype. Clin. Cancer Res., 2014, 20(20), 5182-5193.
[25]
Herrera, A.; Mei, M.; Low, L. Relapsed or refractory double-expressor and double-hit lymphomas have inferior progression-free survival after autologous stem-cell transplantation. J. Clin. Oncol., 2017, 35(1), 24-31.
[26]
Pfreundschuh, M.; Trümper, L.; Osterborg, A. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: A randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol., 2006, 7(5), 379-391.
[27]
Devita, V.; Canellos, G.; Chabner, B.; Schein, P.; Hubbard, S.; Young, R. Advanced diffuse histiocytic lymphoma, a potentially curable disease. Lancet, 1975, 1(7901), 248-250.
[28]
Yi, P.; Coleman, M.; Saltz, L.; Norton, L.; Topilow, A.A.; Adler, K.; Bernhardt, B. Chemotherapy for large cell lymphoma: A status update. Semin. Oncol., 1990, 17, 60-73.
[29]
Roschewski, M.; Staudt, L.M.; Wilson, W.H. Diffuse large B-cell lymphoma-treatment approaches in the molecular era. Nat. Rev. Clin. Oncol., 2013, 11(1), 12-23.
[30]
Kwak, J. Treatment of diffuse large B cell lymphoma. Korean J. Intern. Med., 2012, 27(4), 369-377.
[31]
Crump, M.; Neelapu, S.; Farooq, U. Outcomes in refractory diffuse large B-cell lymphoma: Results from the international scholar-1 study. Blood, 2017, 130(16), 1800-1808.
[32]
Ng, A.; Yahalom, J.; Goda, J.; Constine, L. Role of radiation therapy in patients with relapsed/refractory diffuse large B-cell lymphoma: Guidelines from the International Lymphoma Radiation Oncology Group. Int. J. Radiat. Oncol. Biol. Phys., 2018, 100(3), 652-669.
[33]
Jain, M.; Bachmeier, C.; Phuoc, V.; Chavez, J. Axicabtagene ciloleucel (KTE-C19), an anti-CD19 CAR T therapy for the treatment of relapsed/refractory aggressive B-cell non-Hodgkin’s lymphoma. Ther. Clin. Risk Manag., 2018, 14, 1007-1017.
[34]
Sharma, P.; King, G.; Shinde, S.; Purev, E.; Jimeno, A. Axicabtagene ciloleucel for the treatment of relapsed/refractory B-cell non-Hodgkin’s lymphomas. Drugs Today (Barc), 2018, 54(3), 187-198.
[35]
Neelapu, S.; Locke, F.; Bartlett, N.; Lekakis, L.; Miklos, D.; Jacobson, C. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N. Engl. J. Med., 2017, 377(26), 2531-2544.
[36]
Schuster, S.; Svoboda, J.; Chong, E.; Nasta, S.; Mato, A.; Anak, O. Chimeric antigen receptor T cells in refractory B-cell lymphomas. N. Engl. J. Med., 2017, 377(26), 2545-2554.
[37]
Rhodes, J.; Landsburg, D. Small-molecule inhibitors for the treatment of diffuse large B cell lymphoma. Curr. Hematol. Malig. Rep., 2018, 13(15), 356-368.
[38]
Zahid, U.; Akbar, F.; Amaraneni, A.; Husnain, M.; Chan, O.; Riaz, I.B.; McBride, A.; Iftikhar, A.; Anwer, F. A review of autologous stem cell transplantation in Lymphoma. Curr. Hematol. Malig. Rep., 2017, 12(3), 217-226.
[39]
Roschewski, M.; Staudt, L.M.; Wilson, W.H. Diffuse large B-cell lymphoma[mdash]treatment approaches in the molecular era. Nat. Rev. Clin. Oncol., 2014, 11(1), 12-23.
[40]
Lartigue, J. B-cell receptor signaling pathway emerges as ripe target in many cancers [Internet]. Oncolive, 11 (2017). Available from https://www.onclive.com/publications/oncology-live/2017/vol-18-no-11/
[41]
Khedkar, S.A.; Malde, A.K.; Coutinho, E.C.; Srivastava, S. Pharmacophore modeling in drug discovery and development: An overview. Med. Chem., 2007, 3(2), 187-197.
[42]
Kumar, A.; Zhang, K.Y.J. Hierarchical virtual screening approaches in small molecule drug discovery. Methods, 2015, 71, 26-37.
[43]
Liu, K.; Kokubo, H. Exploring the stability of ligand binding modes to proteins by molecular dynamics simulations: A cross-docking study. J. Chem. Inf. Model., 2017, 57(10), 2514-2522.
[44]
Pagadala, N.S.; Syed, K.; Tuszynski, J. Software for molecular docking: A review. Biophys. Rev., 2017, 9(2), 91-102.
[45]
Childers, M.C.; Daggett, V. Insights from molecular dynamics simulations for computational protein design. Mol. Syst. Des. Eng., 2017, 2(1), 9-33.
[46]
De Vivo, M.; Masetti, M.; Bottegoni, G.; Cavalli, A. Role of molecular dynamics and related methods in drug discovery. J. Med. Chem., 2016, 59(9), 4035-4061.
[47]
Wang, T.; Yuan, X.; Song, W.; Bin, M.; Lin, J.P.; Yang, L.R. The advancement of multidimensional QSAR for novel drug discovery - where are we headed? Expert Opin. Drug Discov., 2017, 12(8), 769-784.
[48]
Abdolmaleki, A.; Ghasemi, J.; Ghasemi, F. Computer aided drug design for multi-target drug design: SAR /QSAR, molecular docking and pharmacophore methods. Curr. Drug Targets, 2017, 18(5), 556-575.
[49]
Rickert, R.C. New insights into pre-BCR and BCR signalling with relevance to B cell malignancies. Nat. Rev. Immunol., 2013, 13(8), 578-591.
[50]
Burger, J.A.; Wiestner, A. Targeting B cell receptor signalling. Nat. Rev. Cancer, 2018, 18(3), 148-167.
[51]
Burger, J.A.; Wiestner, A. Targeting B cell receptor signalling in cancer: preclinical and clinical advances. Nat. Rev. Cancer, 2018, 18(3), 148-167.
[52]
Young, R.M.; Staudt, L.M. Targeting pathological B cell receptor signalling in lymphoid malignancies. Nat. Rev. Drug Discov., 2013, 12, 229-243.
[53]
Young, R.; Shaffer, A.; Phelan, J.; Staudt, L. B cell receptor signaling in diffuse large B cell lymphoma. Semin. Hematol., 2015, 52(2), 77-85.
[54]
Monroe, J. ITAM-mediated tonic signaling through pre-BCR and BCR complexes. Nat. Rev. Immunol., 2006, 6(4), 283-294.
[55]
Iorio, F.; Knijnenburg, T.; Vis, D. A landscape of pharmacogenomic interactions in cancer. Cell, 2016, 166(3), 740-754.
[56]
Nakken, B.; Munthe, L.; Konttinen, Y.T.; Sandberg, A.K.; Szekanecz, Z.; Alex, P.; Szodoray, P. B-cells and their targeting in rheumatoid arthritis-current concepts and future perspectives. Autoimmun. Rev., 2011, 11, 28-34.
[57]
Küppers, R. Mechanisms of B-cell lymphoma pathogenesis. Nat. Rev. Cancer, 2005, 5, 251-262.
[58]
Pan, Z.; Scheerens, H.; Li, S.J.; Schultz, B.E.; Sprengeler, P.A.; Burrill, L.C.; Mendonca, R.V.; Sweeney, M.D.; Scott, K.C.; Grothaus, P.G.; Jeffery, D.A.; Spoerke, J.M.; Honigberg, L.A.; Young, P.R.; Dalrymple, S.A.; Palmer, J.T. Discovery of selective irreversible inhibitors for Bruton’s tyrosine kinase. ChemMedChem, 2007, 2, 58-61.
[59]
Byrd, J.; Furman, R.; Coutre, S.; Flinn, I.; Burger, J.; Blum, K. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N. Engl. J. Med., 2013, 369(1), 32-42.
[60]
Akinleye, A.; Chen, Y.; Mukhi, N.; Song, Y.; Liu, D. Ibrutinib and novel BTK inhibitors in clinical development. J. Hematol. Oncol., 2013, 6, 59.
[61]
Brown, J.R. Ibrutinib (PCI-32765), the first BTK (Bruton’s tyrosine kinase) inhibitor in clinical trials. Curr. Hematol. Malig. Rep., 2013, 8(1), 1-6.
[62]
Xiao, J.; Zhang, S.; Luo, M.; Zou, Y.; Zhang, Y.; Lai, Y. Effective virtual screening strategy focusing on the identification of novel Bruton’s tyrosine kinase. J. Mol. Graph. Model., 2015, 60, 142-154.
[63]
Ge, Y.; Jin, Y.; Wang, C.; Zhang, J.; Tang, Z.; Peng, J.; Liu, K.; Li, Y.; Zhou, Y.; Ma, X. Discovery of novel Bruton’s Tyrosine Kinase (BTK) ihibitors bearing a N,9-diphenyl-9H-purin-2-amine scaffold. ACS Med. Chem. Lett., 2016, 7(12), 1050-1055.
[64]
Bavi, R.; Kumar, R.; Choi, L.; Woo Lee, K. Exploration of novel inhibitor for Bruton’ Tyroine Kinase by 3D QSAR modelling and molecular dynamics simulation. PLoS One, 2016, 11(1)e0147190
[65]
Balasubramanian, P.; Balupuri, A.; Cho, S. Molecular modelling studies on series of Btk inhibitors using docking, structure-based 3D-QSAR and molecular dynamics simulation: A combined approach. Arch. Pharm. Res., 2016, 39(3), 328-339.
[66]
Xue, Y.; Song, P.; Wang, A.; Tong, L.; Geng, M.; Ding, J.; Liu, Q.; Sun, L.; Xie, H.; Zhang, A. Discovery of 4,7-Diamino-5-(4-phenoxyphenyl)-6-methylenepyrimido[5,4 b]pyrrolizines as novel Bruton’s Tyrosin Kinase Inhibitors. J. Med. Chem., 2018, 61(10), 4608-4627.
[67]
Sakthivel, S.; Habeeb, S. Combined pharmacophore, virtual screening and molecular dynamics studies ti identify Bruton’s tyrosine kinase inhibitor. J. Biomol. Struct. Dyn., 2018, 3, 1-18.
[68]
Gold, M.R.; Scheid, M.P.; Santos, L.; Dang-Lawson, M.; Roth, R.A.; Matsuuchi, L.; Duronio, V.; Krebs, D.L. The B cell antigen receptor activates the Akt (protein kinase B)/glycogen synthase kinase-3 signaling pathway via phosphatidylinositol 3-kinase. J. Immunol., 1999, 163(4), 1894-1905.
[69]
LoPiccolo, J.; Blumenthal, G.; Bernstein, W.; Dennis, P. Targeting the PI3K/Akt/mTOR pathway:effective combinations and considerations. Drug Resist. Updat., 2008, 11(1-2), 32-50.
[70]
West, K.; Catillo, S.; Dennis, P. Activation of the PI3K/Akt pathway and chemotherapeuticresitance. Drug Resist. Updat., 2002, 5(6), 234-248.
[71]
Foukas, L.; Berenjeno, I.; Gray, A.; Khwaja, A.; Vanhaesebroeck, B. Activity of any class IA PI3K isoform can sustain cell proliferation and survival. Proc. Natl. Acad. Sci., 2010, 107(25), 11381-11386.
[72]
Jabbour, E.; Ottmann, O.G.; Deininger, M.; Hochhaus, A. Targeting the phosphoinositide 3-kinase pathway in hematologic malignancies. Haematologica, 2014, 99(1), 7-18.
[73]
Younes, A.; Salles, G.; Martinelli, G.; Bociek, R.; Barrigon, D.; Barca, E. Pan-phosphatidylinositol 3-kinase inhibition with buparlisib in patients with relapsed or refractory non-Hodgkin lymphoma. Haematologica, 2017, 102(12), 2104-2112.
[74]
Batlevi, C.; Hamlin, P.; Matasar, M.; Younes, A. Phase I/IB dose escalation and expansion of ibrutinib and buparlisib in relapsed/ refractory diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma. Hematol. Oncol., 2017, 35(S2), 54.
[75]
Deng, C.; Lipstein, M.; Scotto, L.; Jirau Serrano, X.; Mangone, M.; Li, S. Silencing c-Myc translation as a therapeutic strategy through targeting PI3Kδ and CK1ε in hematological malignancies. Blood, 2018, 129(1), 88-99.
[76]
Burris, H., 3rd; Flinn, I.; Patel, M.; Fenske, T.; Deng, C.; Brander, D. Umbralisib, a novel PI3Kdelta and casein kinase- 1epsilon inhibitor, in relapsed or refractory chronic lymphocytic leukemia and lymphoma: An open-label, phase 1, dose-escalation, first-in-human study. Lancet Oncol., 2018, 19(4), 486-496.
[77]
Dreyling, M.; Morschhauser, F.; Bouabdallah, K.; Bron, D.; Cunningham, D.; Assouline, S. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Ann. Oncol., 2017, 28(9), 2169-2178.
[78]
Markham, A. Copanlisib: First global approval. Drugs, 2017, 77(18), 2057-2062.
[79]
Scott, W.J.; Hentemann, M.E.; Rowley, R.B.; Bull, C.O.; Jenkins, S.; Bullion, A.M.; Johnson, J.; Redman, A.; Robbins, A.H.; Esler, W.; Fracasso, R.P.; Garrison, T.; Hamilton, M.; Michels, M.; Wood, J.E.; Wilkie, D.P.; Xiao, H.; Levy, J.; Stasik, E.; Liu, N.; Schaefer, M.; Brands, M.; Lefranc, J. Discovery and SAR novel 2,3-dihydroimidazo[1,2-c]quinazoline PI3K inhibitors: Identification of copanlisib (BAY 80-6946). ChemMedChem, 2016, 11(14), 1517-1530.
[80]
Oluic, J.; Nikolic, K.; Vucicevic, J.; Gagic, Z.; Filipic, S.; Agbaba, D. 3D-QSAR, virtual screening, docking and design of dual PI3K/mtor inhibitors with enhanced antiproliferative activity. Comb. Chem. High Throughput Screen., 2017, 20(4), 292-303.
[81]
Takeda, T.; Wang, Y.; Bryant, S. Structural insights of PI3K/mTOR dual inhibitor with the morpholino-triazine scaffold. J. Comput. Aided Mol. Des., 2016, 30(4), 323-330.
[82]
Rehan, M. A structural insight into the inhibitory mechanism of an orally active PI3K/mTOR dual inhibitor, PKI-179 using computational approaches. J. Mol. Graph. Model., 2015, 62, 226-234.
[83]
Poulsen, A.; Kumar, H.; Lee, A.; Blanchard, S. Structure and ligand-based design of mTOR and PI3-kinase inhibitors leading to the clinical candidates VS-5584 (SB2343) and SB2602. J. Chem. Inf. Model., 2014, 54(11), 3238-3250.
[84]
Chen, L.; Monti, S.; Juszczynski, P.; Daley, J.; Chen, W.; Witzig, T. SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma. Blood, 2008, 111(4), 2230-2237.
[85]
Friedberg, J.W.; Sharman, J.; Sweetenham, J.; Johnston, P.B.; Vose, J.M.; Lacasce, A.; Schaefer-Cutillo, J.; De Vos, S.; Sinha, R.; Leonard, J.P.; Cripe, L.D.; Gregory, S.A.; Sterba, M.P.; Lowe, A.M.; Levy, R.; Shipp, M.A. Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood, 2010, 115(13), 2578-2585.
[86]
Flinn, I.W.; Bartlett, N.L.; Blum, K.A.; Ardeshna, K.M.; LaCasce, A.S.; Flowers, C.R.; Shustov, A.R.; Thress, K.S.; Mitchell, P.; Zheng, F.; Skolnik, J.M.; Friedberg, J.W. A phase II trial to evaluate the efficacy of fostamatinib in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Eur. J. Cancer, 2016, 54, 11-17.
[87]
Kaplan, J.; Gordon, L.; Infante, J.; Popat, R.; Rambaldi, A.; Madan, S. TAK-659, An investigational reversible dual SYK/FLT-3 inhibitor, in patients with lymphoma: updated results from doseescalation and expansion cohorts of a phase 1 study. Hematol. Oncol., 2017, 35(S2), 72-74.
[88]
Huang, Y.; Zhang, Y.; Fan, K.; Dong, G.; Li, B.; Zhang, W.; Li, J.; Sheng, C. Discovery of new Syk inhibitors inhibitors through structure-based virtual screening. Bioorg. Med. Chem. Lett., 2017, 27(8), 1776-1779.
[89]
Kaur, M.; Silakari, O. Identification of new dual spleen tyrosine kinase (Syk) and phosphoionositide-3-kinase& (PI3K&) inhibitors using ligand and structure-based integrated ideal pharmacophore models. SAR QSAR Environ. Res., 2016, 27(6), 469-499.
[90]
Kaur, M.; Silakari, O. Ligand-based and e-pharmacophore modeling, SD-QSAR and hierarchical virtual screening to identify dual inhibitors of spleen tyrosinr kinase (Syk) and janus kinase 3 (JAK3). J. Biomol. Struct. Dyn., 2017, 35(14), 3043-3060.
[91]
Qian, C.; Lai, C.; Bao, R.; Wang, D.G.; Wang, J.; Xu, G.X.; Atoyan, R.; Qu, H.; Yin, L.; Samson, M.; Zifcak, B.; Ma, A.W.; DellaRocca, S.; Borek, M.; Zhai, H.X.; Cai, X.; Voi, M. Cancer network disruption by a single molecule inhibitor targeting both histone deacetylase activity and phosphatidylinositol 3-kinase signaling. Clin. Cancer Res., 2012, 18(15), 4104-4113.
[92]
Pasqualucci, L.; Dominguez-Sola, D.; Chiarenza, A.; Fabbri, G.; Grunn, A.; Trifonov, V. Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature, 2011, 471(7337), 189-195.
[93]
Bereshchenko, O.; Gu, W.; Dalla-Favera, R. Acetylation inactivates the transcriptional repressor BCL6. Nat. Genet., 2002, 32(4), 606-613.
[94]
O’Connor, O.; Horwitz, S.; Masszi, T.; Van Hoof, A.; Brown, P.; Doorduijn, J. Belinostat in patients with relapsed or refractory peripheral T-cell lymphoma: Results of the pivotal phase II BELIEF (CLN-19) study. J. Clin. Oncol., 2015, 33(23), 2492-2499.
[95]
Coiffier, B.; Pro, B.; Prince, H.; Foss, F.; Sokol, L.; Greenwood, M. Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J. Clin. Oncol., 2012, 30(6), 631-636.
[96]
Mann, B.; Johnson, J.; He, K.; Sridhara, R.; Abraham, S.; Booth, B. Vorinostat for treatment of cutaneousmanifestations of advanced primary cutaneous T-cell lymphoma. Clin. Cancer Res., 2007, 13(8), 2318-2322.
[97]
Batlevi, C.L.; Crump, M.; Andreadis, C.; Rizzieri, D.; Assouline, S.E.; Fox, S.; van der Jagt, R.H.C.; Copeland, A.; Potvin, D.; Chao, R.; Younes, A. A phase 2 study of mocetinostat, a histone deacetylase inhibitor, in relapsed or refractory lymphoma. Br. J. Haematol., 2017, 178(3), 434-441.
[98]
Haji Agha Bozorghi, A.; Zarghi, A. Search for the pharmacophore of histone deacetylase inhibitors using pharmacophore query and docking study. Iran. J. Pharm. Res., 2014, 13(4), 1165-1172.
[99]
Patel, P.; Singh, A.; Patel, V.; Jain, D.; Veerasamy, R.; Rajak, H. Pharmacophore based 3D-QSAR, virtual screening and docking studies on novel series of HDAC inhibitors with thiophen linker as anticancer agents. Comb. Chem. High Throughput Screen., 2016, 19(9), 735-751.
[100]
Huang, Y.X.; Zhao, J.; Song, Q.H.; Zheng, L.H.; Fan, C.; Liu, T.T.; Bao, Y.L.; Sun, L.G.; Zhang, L.B.; Li, Y.X. Virtual screening and experimental validation of novel histone deacetylase inhibitors. BMC Pharmacol. Toxicol., 2016, 17, 32.
[101]
Panwalkar, A.; Verstovsek, S.; Giles, F.J. Mammalian target of rapamycin inhibition as therapy for hematologic malignancies. Cancer, 2004, 100(4), 657-666.
[102]
Wanner, K.; Hipp, S.; Oelsner, M.; Bogner, C.; Ringshausen, I.; Peschel, C. Mammalian target of rapamycin inhibition induces cell cycle arrest in diffuse large B cell lymphoma (DLBCL) cells and sensitizes DLBCL cells to rituximab. Br. J. Haematol., 2006, 134(5), 475-484.
[103]
Argyriou, P.; Economopoulou, P.; Papageorgiou, S. The role of mTOR inhibitors for the treatment of B-cell lymphomas. Adv. Hematol., 2012, 2012Article ID 435342
[104]
Hudes, G.; Carducci, M.; Tomczak, P.; Dutcher, J.; Figlin, R.; Kapoor, A. Temsirolimus, interferon Alfa, or both for advanced renal cell carcinoma. N. Engl. J. Med., 2007, 356(22), 2271-2281.
[105]
Hess, G.; Herbrecht, R.; Romaguera, J.; Verhoef, G.; Gisselbrecht, C.; Crump, M. Phase III study to evaluate temsirolimus compared with investigator’s choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J. Clin. Oncol., 2009, 27(23), 3822-3829.
[106]
Witzens-Harig, M.; Viardot, A.; Keller, U.; Buske, C.; Honig, E.; Atta, J. Safety and clinical activity of temsirolimus in combination with rituximab and DHAP in patients with relapsed or refractory diffuse large B-cell lymphoma-report of the prospective, multicenter phase II storm trial. Hematol. Oncol., 2017, 35(S2), 191.
[107]
Barnes, J.; Jacobsen, E.; Feng, Y.; Freedman, A.; Hochberg, E.; LaCasce, A. Everolimus in combination with rituximab induces complete responses in heavily pretreated diffuse large B-cell lymphoma. Haematologica, 2013, 98(4), 615-619.
[108]
Johnston, P.; LaPlant, B.; McPhail, E.; Habermann, T.; Inwards, D.; Micallef, I. Everolimus combined with R-CHOP-21 for new, untreated, diffuse large B-cell lymphoma (NCCTG 1085 [Alliance]): Safety and efficacy results of a phase 1 and feasibility trial. Lancet Haematol., 2016, 3(7), e309-e316.
[109]
Kist, R.; Caceres, R. New potential inhibitors of mTOR: a computational investigation integrating molecular docking, virtual screening and molecular dynamics simulation. J. Biomol. Struct. Dyn., 2017, 35(16), 3555-3568.
[110]
Wang, L.; Chen, L.; Yu, M.; Xu, L.H.; Cheng, B.; Lin, Y.S.; Gu, Q.; He, X.H.; Xu, J. Discovering new mTOR inhibitors for cancer treatment through virtual screening methods and in vitro assays. Sci. Rep., 2016, 6, 18987.
[111]
Xie, H.; Lee, M-H.; Zhu, F.; Reddy, K.; Huang, Z.; Kim, D.J.; Li, Y.; Peng, C.; Lim, D.Y.; Kang, S.; Jung, S.K.; Li, X.; Li, H.; Ma, W.; Lubet, R.A.; Ding, J.; Bode, A.M.; Dong, Z. Discovery of the novel mTOR inhibitor and its antitumor activities in vitro and in vivo. Mol. Cancer Ther., 2013, 12(6), 950-958.
[112]
Proteomics, M.O.J. Molecular docking and pharmacokinetic of highly specific novel pan-mtor inhibitors against solid tumors. MOJ Proteom. Bioinform., 2017, 5(6), 13-16.
[113]
Huang, J.; Sanger, W.; Greiner, T.; Staudt, L.; Weisenburger, D.; Pickering, D. The t(14;18) defines a unique subset of diffuse large B-cell lymphoma with a germinal center B-cell gene expression profile. Blood, 2002, 99(7), 2285-2290.
[114]
Roberts, A.; Huang, D.C.S. Targeting BCL2 With BH3Mimetics: Basic science and clinical application of venetoclax in chronic lymphocytic leukemia and related B cell malignancies. Clin. Pharmacol. Ther., 2017, 101(1), 89-98.
[115]
Davids, M.; Roberts, A.; Seymour, J.; Pagel, J.; Kahl, B.; Wierda, W. Phase I first-in-human study of venetoclax in patients with relapsed or refractory non Hodgkin lymphoma. J. Clin. Oncol., 2017, 35(8), 826-833.
[116]
Zelenetz, A.; Salles, G.; Mason, K.; Casulo, C.; Le Gouill, S.; Sehn, L. Results of a phase Ib study of venetoclax plus R- or GCHOP in patients with B-cell non-Hodgkin lymphoma. Blood, 2016, 128(22), 3032.
[117]
Ahmed, M.; Jamil, K. BCL-2 as target for molecular docking of some neoplastic drugs. Sci. Rep., 2012, 1, 458.
[118]
Ziedan, N.; Hamdy, R.; Cvaliere, A.; Kourti, M.; Prencipe, F.; Brancale, A.; Jones, A.T.; Westwell, A.D. Virtual screening, SAR, and discovery of 5-(indole-3-yl)-2-[(2-nitrophenyl)amino] [1,3,4]-oxadiazole as a novel Bcl-2 inhibitor. Chem. Biol. Drug Des., 2017, 90(1), 147-155.
[119]
Jamei, M.; Khoshneviszadeh, M.; Edraki, N.; Firoozi, M.; Haghighijoo, Z.; Sakhtaman, A. Cross docking study directed toward virtual screening and molecular docking study of phenanthrene 1,2,4-triazine derivatives as novel Bcl-2 inhibitors. TRENDS Pharm. Sci., 2016, 2, 4.
[120]
Olotu, F.A.; Agoni, C.; Adeniji, E.; Abdullahi, M.; Soliman, M.E. Probing gallate-mediated selectivity and high-affinity binding of epigallocatechin gallate: A way-forward in the design of selective inhibitors for anti-apoptotic Bcl-2 proteins. Appl. Biochem. Biotechnol., 2019, 187(3), 1061-1080.
[121]
Dou, Q.; Li, B. Proteasome inhibitors as potential novel anticancer agents. Drug Resist. Updat., 1999, 2(4), 215-223.
[122]
Adams, J. The proteasome: A suitable antineoplastic target. Nat. Rev. Cancer, 2004, 4(5), 349-360.
[123]
Roff, M.; Thompson, J.; Rodriguez, M.; Jacque, J-M.; Baleux, F.; Arenzana-Seisdedos, F. Role of IB ubiquitination in signalinduced activation of NF-B in vivo. J. Biol. Chem., 1996, 271(13), 7844-7850.
[124]
Mato, A.; Feldman, T.; Goy, A. Proteasome inhibition and combination therapy for Non-Hodgkin’s Lymphoma: From bench to bedside. Oncologist, 2012, 7, 694-707.
[125]
Niesvizky, R.; Flinn, I.; Rifkin, R.; Gabrail, N.; Charu, V.; Clowney, B. Phase 3b upfront study: Safety and efficacy of weekly bortezomib maintenance therapy after bortezomib-based induction regimens in elderly, Newly diagnosed multiple myeloma patients. Blood, 2010, 116(21), 619.
[126]
Richardson, P.; Barlogie, B.; Berenson, J.; Singhal, S.; Jagannath, S.; Irwin, D. A phase 2 study of bortezomib in relapsed, refractory myeloma. N. Engl. J. Med., 2003, 348(26), 2609-2617.
[127]
Bose, P.; Batalo, M.; Holkova, B.; Grant, S. Bortezomib for the treatment of non-Hodgkin’s lymphoma. Expert Opin. Pharmacother., 2016, 15(16), 2443-2459.
[128]
Kupperman, E.; Lee, E.; Cao, Y.; Bannerman, B.; Fitzgerald, M.; Berger, A. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res., 2010, 70(5), 1970-1980.
[129]
Lee, E.; Fitzgerald, M.; Bannerman, B.; Donelan, J.; Bano, K.; Terkelsen, J. Antitumor activity of the investigational proteasome inhibitor MLN9708 in mouse models of B-cell and plasma cell malignancies. Clin. Cancer Res., 2011, 17(23), 7313-7323.
[130]
Liu, W.; Chen, Y.; Tamayo, A.; Ruan, C.; Li, L.; Zhou, S.; Shen, C.; Young, K.H.; Westin, J.; Davis, R.E.; Hu, S.; Medeiros, L.J.; Ford, R.J.; Pham, L.V. Preclinical efficacy and biological effects of the oral proteasome inhibitor ixazomib in diffuse large B-cell lymphoma. Oncotarget, 2018, 9(1), 346-360.
[131]
Khan, M.; Stewart, A. Carfilzomib: A novel second-generation proteasome inhibito. Future Oncol., 2011, 7(5), 607-612.
[132]
Kubiczkova, L.; Pour, L.; Sedlarikova, L.; Hajek, R.; Sevcikova, S. Proteasome inhibitors - molecular basis and current perspectives in multiple myeloma. J. Cell. Mol. Med., 2014, 18(6), 947-961.
[133]
Miller, Z.; Kim, K.S.; Lee, D.M.; Kasam, V.; Baek, S.E.; Lee, K.H.; Zhang, Y.Y.; Ao, L.; Carmony, K.; Lee, N.R.; Zhou, S.; Zhao, Q.; Jang, Y.; Jeong, H.Y.; Zhan, C.G.; Lee, W.; Kim, D.E.; Kim, K.B. Proteasome Inhibitors with pyrazole scaffolds from structure-based virtual screening. J. Med. Chem., 2015, 58(4), 2036-2041.
[134]
Di Giovanni, C.; Ettari, R.; Sarno, S.; Rotondo, A.; Bitto, A.; Squadrito, F.; Altavilla, D.; Schirmeister, T.; Novellino, E.; Grasso, S.; Zappalà, M.; Lavecchia, A. Identification of noncovalent proteasome inhibitors with high selectivity for chymotrypsin-like activity by a multistep structure-based virtual screening. Eur. J. Med. Chem., 2016, 121, 578-591.
[135]
Arba, M.; Nur-Hidayat, A.; Surantaadmaja, S.; Tjahjono, D. Pharmacophore-based virtual screening for identifying β5 subunit inhibitor of 20S proteasome. Comput. Biol. Chem., 2018, 77, 64-71.
[136]
Guedes, R.; Serra, P.; Salvador, J.; Guedes, R. Computational approaches for the discovery of human proteasome inhibitors: An overview. Molecules, 2016, 21(7)pii E927
[137]
Bender, A.; Gardberg, A.; Pareira, A.; Johnson, T.; Wu, Y.; Grenningloh, R.; Head, J.; Morandi, F.; Haselmayer, P.; Liu-Bujalski, L. Ability of Bruton’s tyrosine kinase inhibitors to sequester Y551 and prevent phosphorylation determines potency for inhibition of Fc receptor but not B-cell receptor signaling. Mol. Pharmacol., 2017, 91, 208-219.
[138]
Lee, S.; Choi, J.S.; Han, B.G.; Kim, H.S.; Song, H.J.; Lee, J.; Nam, S.; Goh, S.H.; Kim, J.H.; Koh, J.S.; Lee, B.I. Crystal structures of spleen tyrosine kinase in complex with novel inhibitors: Structural insights for design of anticancer drugs. FEBS J., 2016, 283, 3613-3625.
[139]
Song, K.; Yang, X.; Zhao, Y.; Jian, Z. Crystal structure of PI3K complex with an inhibitor. https://www.rcsb.org/structure/5XGI (yet to published). DOI: 10.2210/pdb5XGI/pdb. Date Accessed: 2019-08-25.
[140]
Whitehead, L.; Dobler, M.; Radetich, B.; Zhu, Y.; Atadja, P.W.; Claiborne, T.; Grob, J.E.; McRiner, A.; Pancost, M.R.; Patnaik, A.; Shao, W.; Shultz, M.; Tichkule, R.; Tommasi, R.A.; Vash, B.; Wang, P.; Stams, T. Human HDAC isoform selectivity achieved via exploitation of the acetate release channel with structurally unique small molecule inhibitors. Bioorg. Med. Chem., 2011, 19, 4626-4634.
[141]
Perez, H.L.; Banfi, P.; Bertrand, J.; Cai, Z.W.; Grebinski, J.W.; Kim, K.; Lippy, J.; Modugno, M.; Naglich, J.; Schmidt, R.J.; Tebben, A.; Vianello, P.; Wei, D.D.; Zhang, L.; Galvani, A.; Lombardo, L.J.; Borzilleri, R.M. Identification of a phenylacylsulfonamide series of dual Bcl-2/Bcl-Xl antagonists. Bioorg. Med. Chem. Lett., 2012, 22, 3946.
[142]
Lau, W.; Li, Y.; Liu, Z.; Gao, Y.; Zhang, Q.; Huen, M. Crystal structure of mTOR docked into EM map of dimeric ATM kinase. Cell Cycle, 2016, 15, 1117-1124.
[143]
Harshbarger, W.; Miller, C.; Diedrich, C.; Sacchettini, J. Crystal Structure of the human 20S proteasome in complex with carfilzomib. Structure, 2015, 23, 418-424.

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