Novel benzo chromene derivatives: design, synthesis, molecular docking, cell cycle arrest, and apoptosis induction in human acute myeloid leukemia HL-60 cells

References

• Dohner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015;373(12):1136–1152.
   PubMed Web of Science ®Google Scholar
• De Kouchkovsky I, Abdul-Hay M. Acute myeloid leukemia: a comprehensive review and 2016 update. Blood Cancer J. 2016;6(7):e441.
   PubMed Web of Science ®Google Scholar
• Pelcovits A, Niroula R. Acute myeloid leukemia: a review. R I Med J. 2020;103(3):38–40.
   Google Scholar
• Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA A Cancer J Clinicians. 2022;72(1):7–33.
   PubMed Web of Science ®Google Scholar
• Ni W, Qian W, Tong X. Cryptotanshinone induces apoptosis of HL-60 cells via mitochondrial pathway. Trop J Pharm Res. 2014;13(4):545.
   Web of Science ®Google Scholar
• Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, Bloomfield CD, Thiede C, Prior TW, Dohner K, Marcucci G, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a flt3 mutation. N Engl J Med. 2017;377(5):454–464.
   PubMed Web of Science ®Google Scholar
• Perl AE, Martinelli G, Cortes JE, Neubauer A, Berman E, Paolini S, Montesinos P, Baer MR, Larson RA, Ustun C, et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated aml. N Engl J Med. 2019;381(18):1728–1740.
   PubMed Web of Science ®Google Scholar
• DiNardo CD, Stein EM, de Botton S, Roboz GJ, Altman JK, Mims AS, Swords R, Collins RH, Mannis GN, Pollyea DA, et al. Durable remissions with Ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med. 2018;378(25):2386–2398.
   PubMed Web of Science ®Google Scholar
• Stein EM, DiNardo CD, Pollyea DA, Fathi AT, Roboz GJ, Altman JK, Stone RM, DeAngelo DJ, Levine RL, Flinn IW, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017;130(6):722–731.
   PubMed Web of Science ®Google Scholar
• Stein EM. Enasidenib, a targeted inhibitor of mutant IDH2 proteins for treatment of relapsed or refractory acute myeloid leukemia. Future Oncol. 2018;14(1):23–40.
   PubMed Web of Science ®Google Scholar
• DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133(1):7–17.
   PubMed Web of Science ®Google Scholar
• Wei AH, Strickland SA, Jr, Hou JZ, Fiedler W, Lin TL, Walter RB, Enjeti A, Tiong IS, Savona M, Lee S, et al. Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: results from a phase IB/II study. J Clin Oncol. 2019;37(15):1277–1284.
   PubMed Web of Science ®Google Scholar
• Zeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland SA, Lancet JE, Bose P, Levy MY, Tibes R, et al. Final results of a randomized multicenter phase ii study of alvocidib, cytarabine, and mitoxantrone versus cytarabine and daunorubicin (7 + 3) in newly diagnosed high-risk acute myeloid leukemia (AML). Leuk Res. 2018;72:92–95.
   PubMed Web of Science ®Google Scholar
• Zeidner JF, Karp JE. Clinical activity of alvocidib (flavopiridol) in acute myeloid leukemia. Leuk Res. 2015;39(12):1312–1318.
   PubMed Web of Science ®Google Scholar
• Zeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland SA, Lancet JE, Bose P, Levy MY, Tibes R, et al. Randomized multicenter phase ii study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (flam) versus cytarabine/daunorubicin (7 + 3) in newly diagnosed acute myeloid leukemia. Haematologica. 2015;100(9):1172–1179.
   PubMed Web of Science ®Google Scholar
• Frame S, Saladino C, MacKay C, Atrash B, Sheldrake P, McDonald E, Clarke PA, Workman P, Blake D, Zheleva D. Fadraciclib (cyc065), a novel cdk inhibitor, targets key pro-survival and oncogenic pathways in cancer. PLoS One. 2020;15(7):e0234103.
   PubMed Web of Science ®Google Scholar
• Decker RH, Dai Y, Grant S. The cyclin-dependent kinase inhibitor flavopiridol induces apoptosis in human leukemia cells (u937) through the mitochondrial rather than the receptor-mediated pathway. Cell Death Differ. 2001;8(7):715–724.
   PubMed Web of Science ®Google Scholar
• Czabotar PE, Lessene G, Strasser A, Adams JM. Control of apoptosis by the Bcl-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol. 2014;15(1):49–63.
   PubMed Web of Science ®Google Scholar
• Bhola PD, Letai A. Mitochondria-judges and executioners of cell death sentences. Mol Cell. 2016;61(5):695–704.
   PubMed Web of Science ®Google Scholar
• Callagy GM, Pharoah PD, Pinder SE, Hsu FD, Nielsen TO, Ragaz J, Ellis IO, Huntsman D, Caldas C. Bcl-2 is a prognostic marker in breast cancer independently of the Nottingham prognostic index. Clin Cancer Res. 2006;12(8):2468–2475.
   PubMed Web of Science ®Google Scholar
• Catz SD, Johnson JL. Bcl-2 in prostate cancer: a minireview. Apoptosis. 2003;8(1):29–37.
   PubMed Web of Science ®Google Scholar
• Nunez G, Seto M, Seremetis S, Ferrero D, Grignani F, Korsmeyer SJ, Dalla-Favera R. Growth- and tumor-promoting effects of deregulated Bcl2 in human b-lymphoblastoid cells. Proc Natl Acad Sci USA. 1989;86(12):4589–4593.
   PubMed Web of Science ®Google Scholar
• Tsujimoto Y, Cossman J, Jaffe E, Croce CM. Involvement of the Bcl-2 gene in human follicular lymphoma. Science. 1985;228(4706):1440–1443.
   PubMed Web of Science ®Google Scholar
• Zhang H, Xue J, Hessler P, Tahir SK, Chen J, Jin S, Souers AJ, Leverson JD, Lam LT. Genomic analysis and selective small molecule inhibition identifies Bcl-x(l) as a critical survival factor in a subset of colorectal cancer. Mol Cancer. 2015; 14:126.
   PubMed Web of Science ®Google Scholar
• Cho-Vega JH, Rassidakis GZ, Admirand JH, Oyarzo M, Ramalingam P, Paraguya A, McDonnell TJ, Amin HM, Medeiros LJ. Mcl-1 expression in b-cell non-Hodgkin’s lymphomas. Hum Pathol. 2004;35(9):1095–1100.
   PubMed Web of Science ®Google Scholar
• Song L, Coppola D, Livingston S, Cress D, Haura EB. Mcl-1 regulates survival and sensitivity to diverse apoptotic stimuli in human non-small cell lung cancer cells. Cancer Biol Ther. 2005;4(3):267–276.
   PubMed Web of Science ®Google Scholar
• Zhang H, Guttikonda S, Roberts L, Uziel T, Semizarov D, Elmore SW, Leverson JD, Lam LT. Mcl-1 is critical for survival in a subgroup of non-small-cell lung cancer cell lines. Oncogene. 2011;30(16):1963–1968.
   PubMed Web of Science ®Google Scholar
• Zhang B, Gojo I, Fenton RG. Myeloid cell factor-1 is a critical survival factor for multiple myeloma. Blood. 2002;99(6):1885–1893.
   PubMed Web of Science ®Google Scholar
• Rassidakis GZ, Lai R, McDonnell TJ, Cabanillas F, Sarris AH, Medeiros LJ. Overexpression of Mcl-1 in anaplastic large cell lymphoma cell lines and tumors. Am J Pathol. 2002;160(6):2309–2310.
   PubMed Web of Science ®Google Scholar
• Placzek WJ, Wei J, Kitada S, Zhai D, Reed JC, Pellecchia M. A survey of the anti-apoptotic bcl-2 subfamily expression in cancer types provides a platform to predict the efficacy of Bcl-2 antagonists in cancer therapy. Cell Death Dis. 2010;1:e40.
   PubMed Web of Science ®Google Scholar
• Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, et al. The landscape of somatic copy-number alteration across human cancers. Nature. 2010;463(7283):899–905.
   PubMed Web of Science ®Google Scholar
• Kelly PN, Strasser A. The role of bcl-2 and its pro-survival relatives in tumourigenesis and cancer therapy. Cell Death Differ. 2011;18(9):1414–1424.
   PubMed Web of Science ®Google Scholar
• Miyamoto Y, Hosotani R, Wada M, Lee JU, Koshiba T, Fujimoto K, Tsuji S, Nakajima S, Doi R, Kato M, et al. Immunohistochemical analysis of bcl-2, bax, bcl-x, and mcl-1 expression in pancreatic cancers. Oncology. 1999;56(1):73–82.
   PubMed Web of Science ®Google Scholar
• Strasser A, Harris AW, Bath ML, Cory S. Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2. Nature. 1990;348(6299):331–333.
   PubMed Web of Science ®Google Scholar
• Deng J. How to unleash mitochondrial apoptotic blockades to kill cancers? Acta Pharm Sin B. 2017;7(1):18–26.
   PubMed Web of Science ®Google Scholar
• Huang Q, Wang L, Ran Q, Wang J, Wang C, He H, Li L, Qi H. Notopterol-induced apoptosis and differentiation in human acute myeloid leukemia HL-60 cells. Drug Des Devel Ther. 2019;13:1927–1940.
   PubMed Web of Science ®Google Scholar
• Lin B, Kolluri SK, Lin F, Liu W, Han YH, Cao X, Dawson MI, Reed JC, Zhang XK. Conversion of bcl-2 from protector to killer by interaction with nuclear orphan receptor nur77/tr3. Cell. 2004;116(4):527–540.
   PubMed Web of Science ®Google Scholar
• Vakamullu S, Arepalli SK, Velatooru LR, Venkateswara Rao J, Kavin Kennedy P, Narsaiah B. In vitro apoptotic mechanism of a novel synthetic quinazolinyl derivative: Induces caspase-dependent intrinsic pathway on THP-1, leukemia cell line. Chem Biol Interact. 2018;280:117–127.
   PubMed Web of Science ®Google Scholar
• Boatright KM, Salvesen GS. Mechanisms of caspase activation. Curr Opin Cell Biol. 2003;15(6):725–731.
   PubMed Web of Science ®Google Scholar
• Desagher S, Martinou JC. Mitochondria as the central control point of apoptosis. Trends Cell Biol. 2000;10(9):369–377.
   PubMed Web of Science ®Google Scholar
• Nagata S. Fas ligand-induced apoptosis. Annu Rev Genet. 1999; 33:29–55.
   PubMed Web of Science ®Google Scholar
• Kemnitzer W, Drewe J, Jiang S, Zhang H, Zhao J, Crogan-Grundy C, Xu L, Lamothe S, Gourdeau H, Denis R, et al. Discovery of 4-aryl-4h-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 3. Structure-activity relationships of fused rings at the 7,8-positions. J Med Chem. 2007;50(12):2858–2864.
   PubMed Web of Science ®Google Scholar
• Gourdeau H, Leblond L, Hamelin B, Desputeau C, Dong K, Kianicka I, Custeau D, Boudreau C, Geerts L, Cai SX, et al. Antivascular and antitumor evaluation of 2-amino-4-(3-bromo-4,5-dimethoxy-phenyl)-3-cyano-4h-chromenes, a novel series of anticancer agents. Mol Cancer Ther. 2004;3(11):1375–1384.
   PubMed Web of Science ®Google Scholar
• Pei XY, Dai Y, Grant S. The small-molecule bcl-2 inhibitor ha14-1 interacts synergistically with flavopiridol to induce mitochondrial injury and apoptosis in human myeloma cells through a free radical-dependent and jun nh2-terminal kinase-dependent mechanism. Mol Cancer Ther. 2004;3(12):1513–1524.
   PubMed Web of Science ®Google Scholar
• Fischer U, Schulze-Osthoff K. Apoptosis-based therapies and drug targets. Cell Death Differ. 2005;12(Suppl 1):942–961.
   PubMed Web of Science ®Google Scholar
• Doshi JM, Tian D, Xing C. Structure-activity relationship studies of ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4h-chromene-3-carboxylate (ha 14-1), an antagonist for antiapoptotic bcl-2 proteins to overcome drug resistance in cancer. J Med Chem. 2006;49(26):7731–7739.
   PubMed Web of Science ®Google Scholar
• Sayed M, Essam Y, Awad E-D, El-Hallouty S, El-Araby M. Design, synthesis and cancer cell line activities of pyrazolo[3,4-b]pyridine derivatives. Open J Med Chem. 2012;2(3):78–88.
   Google Scholar
• Fatahala SS, Mohamed MS, Youns M, Abd-El Hameed RH. Synthesis and evaluation of cytotoxic activity of some pyrroles and fused pyrroles. Anticancer Agents Med Chem. 2017;17(7):1014–1025.
   PubMed Web of Science ®Google Scholar
• Rania H Abd El-Hameed, Amira I. Sayed. Synthesis of novel pyrrolopyrimidine derivatives as cdk 2 inhibitors. Pharmacophore. 2018;9(5):29–49.
   Google Scholar
• Awad SM, Mohamed MS, Khodair MAE, El-Hameed RHA. Synthesis and evaluation of cytotoxic activity of certain benzo[h]chromene derivatives. Anticancer Agents Med Chem. 2021;21(8):963–986.
   PubMed Web of Science ®Google Scholar
• Kamdar NR, Haveliwala DD, Mistry PT, Patel SK. Synthesis and evaluation of in vitro antitubercular activity and antimicrobial activity of some novel 4h-chromeno[2,3-d]pyrimidine via 2-amino-4-phenyl-4h-chromene-3-carbonitriles. Med Chem Res. 2011;20(7):854–864.
   Web of Science ®Google Scholar
• Kamdar NR, Haveliwala DD, Mistry PT, Patel SK. Design, synthesis and in vitro evaluation of antitubercular and antimicrobial activity of some novel pyranopyrimidines. Eur J Med Chem. 2010;45(11):5056–5063.
   PubMed Web of Science ®Google Scholar
• Solhy A, Elmakssoudi A, Tahir R, Karkouri M, Larzek M, Bousmina MM, Zahouily M. Clean chemical synthesis of 2-amino-chromenes in water catalyzed by nanostructured diphosphate Na2CaP2O7. ChemInform. 2011;42(17):2.
   Google Scholar
• Evans BE, Rittle KE, Bock MG, DiPardo RM, Freidinger RM, Whitter WL, Lundell GF, Veber DF, Anderson PS, Chang RS. Methods for drug discovery: development of potent, selective, orally effective cholecystokinin antagonists. J Med Chem. 1988;31(12):2235–2246.
   PubMed Web of Science ®Google Scholar
• Boyd MR, Paull KD. Some practical considerations and applications of the national cancer institute in vitro anticancer drug discovery screen. Drug Dev Res. 1995;34(2):91–109.
   Web of Science ®Google Scholar
• Kalalbandi VKA, Seetharamappa J, Katrahalli U, Bhat KG. Synthesis, crystal studies, anti-tuberculosis and cytotoxic studies of 1-[(2e)-3-phenylprop-2-enoyl]-1h-benzimidazole derivatives. Eur J Med Chem. 2014;79:194–202.
   PubMed Web of Science ®Google Scholar
• Sherr CJ. G1 phase progression: cycling on cue. Cell. 1994;79(4):551–555.
   PubMed Web of Science ®Google Scholar
• Tsytlonok M, Sanabria H, Wang Y, Felekyan S, Hemmen K, Phillips AH, Yun MK, Waddell MB, Park CG, Vaithiyalingam S, et al. Dynamic anticipation by CDK2/cyclin a-bound p27 mediates signal integration in cell cycle regulation. Nat Commun. 2019;10(1):1676.
   PubMedGoogle Scholar
• Neganova I, Vilella F, Atkinson SP, Lloret M, Passos JF, von Zglinicki T, O'Connor JE, Burks D, Jones R, Armstrong L, et al. An important role for CDK2 in G1 to S checkpoint activation and DNA damage response in human embryonic stem cells. Stem Cells. 2011;29(4):651–659.
   PubMed Web of Science ®Google Scholar
• Ying M, Shao X, Jing H, Liu Y, Qi X, Cao J, Chen Y, Xiang S, Song H, Hu R, et al. Ubiquitin-dependent degradation of CDK2 drives the therapeutic differentiation of AML by targeting PRDX2. Blood. 2018;131(24):2698–2711.
   PubMed Web of Science ®Google Scholar
• Burdette-Radoux S, Tozer RG, Lohmann RC, Quirt I, Ernst DS, Walsh W, Wainman N, Colevas AD, Eisenhauer EA. Phase II trial of flavopiridol, a cyclin dependent kinase inhibitor, in untreated metastatic malignant melanoma. Invest New Drugs. 2004;22(3):315–322.
   PubMed Web of Science ®Google Scholar
• Carlson BA, Dubay MM, Sausville EA, Brizuela L, Worland PJ. Flavopiridol induces g1 arrest with inhibition of cyclin-dependent kinase (CDK) 2 and CDK4 in human breast carcinoma cells. Cancer Res. 1996;56(13):2973–2978.
   PubMed Web of Science ®Google Scholar
• Omer FAA, Hashim NBM, Ibrahim MY, Dehghan F, Yahayu M, Karimian H, Salim LZA, Mohan S. Beta-mangostin from cratoxylum arborescens activates the intrinsic apoptosis pathway through reactive oxygen species with downregulation of the HSP70 gene in the HL60 cells associated with a G0/G1 cell-cycle arrest. Tumour Biol. 2017;39(11):1010428317731451.
   Google Scholar
• Husain I, Bala K, Wani A, Makhdoomi U, Malik F, Sharma A. Arginase purified from endophytic pseudomonas aeruginosa IH2: Induce apoptosis through both cell cycle arrest and MMP loss in human leukemic HL-60 cells. Chem Biol Interact. 2017;274:35–49.
   PubMed Web of Science ®Google Scholar
• Flinn IW, Byrd JC, Bartlett N, Kipps T, Gribben J, Thomas D, Larson RA, Rai K, Petric R, Ramon-Suerez J, et al. Flavopiridol administered as a 24-hour continuous infusion in chronic lymphocytic leukemia lacks clinical activity. Leuk Res. 2005;29(11):1253–1257.
   PubMed Web of Science ®Google Scholar
• Phelps MA, Lin TS, Johnson AJ, Hurh E, Rozewski DM, Farley KL, Wu D, Blum KA, Fischer B, Mitchell SM, et al. Clinical response and pharmacokinetics from a phase 1 study of an active dosing schedule of flavopiridol in relapsed chronic lymphocytic leukemia. Blood. 2009;113(12):2637–2645.
   PubMed Web of Science ®Google Scholar
• Shirsath NP, Manohar SM, Joshi KS. P276-00, a cyclin-dependent kinase inhibitor, modulates cell cycle and induces apoptosis in vitro and in vivo in mantle cell lymphoma cell lines. Mol Cancer. 2012;11:77.
   PubMed Web of Science ®Google Scholar
• Cassaday RD, Goy A, Advani S, Chawla P, Nachankar R, Gandhi M, Gopal AK. A phase II, single-arm, open-label, multicenter study to evaluate the efficacy and safety of p276-00, a cyclin-dependent kinase inhibitor, in patients with relapsed or refractory mantle cell lymphoma. Clin Lymphoma Myeloma Leuk. 2015;15(7):392–397.
   PubMed Web of Science ®Google Scholar
• Wood DJ, Korolchuk S, Tatum NJ, Wang LZ, Endicott JA, Noble MEM, Martin MP. Differences in the conformational energy landscape of CDK1 and CDK2 suggest a mechanism for achieving selective CDK inhibition. Cell Chem Biol. 2019;26(1):121–130.e125.
   PubMed Web of Science ®Google Scholar
• De Azevedo WF, Jr., Mueller-Dieckmann HJ, Schulze-Gahmen U, Worland PJ, Sausville E, Kim SH. Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase. Proc Natl Acad Sci USA. 1996;93(7):2735–2740.
   PubMed Web of Science ®Google Scholar
• Ahn YM, Vogeti L, Liu CJ, Santhapuram HK, White JM, Vasandani V, Mitscher LA, Lushington GH, Hanson PR, Powell DR, et al. Design, synthesis, and antiproliferative and CDK2-cyclin A inhibitory activity of novel flavopiridol analogues. Bioorg Med Chem. 2007;15(2):702–713.
   PubMed Web of Science ®Google Scholar
• Kolosov MA, Orlov VD, Kolos NN, Shishkin OV, Zubatyuk RI. Reactions of α-cyanochalcones with phenylhydrazine. Arkivoc. 2007;2007(16):187–194.
   Google Scholar
• Mohamed MS, El-Domany RA, Abd El-Hameed RH. Synthesis of certain pyrrole derivatives as antimicrobial agents. Acta Pharm. 2009;59(2):145–158.
   PubMed Web of Science ®Google Scholar
• Bhuiyan MD, Rahman KM, Hossain MD, Rahim A, Hossain MI, Abu Naser M. Synthesis and antimicrobial evaluation of some new thienopyrimidine derivatives. Acta Pharm. 2006;56(4):441–450.
   PubMedGoogle Scholar
• Massague J. G1 cell-cycle control and cancer. Nature. 2004;432(7015):298–306.
   PubMed Web of Science ®Google Scholar
• Youle RJ, Strasser A. The bcl-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 2008;9(1):47–59.
   PubMed Web of Science ®Google Scholar
• Garner TP, Lopez A, Reyna DE, Spitz AZ, Gavathiotis E. Progress in targeting the Bcl-2 family of proteins. Curr Opin Chem Biol. 2017;39:133–142.
   PubMed Web of Science ®Google Scholar
• Willis SN, Fletcher JI, Kaufmann T, van Delft MF, Chen L, Czabotar PE, Ierino H, Lee EF, Fairlie WD, Bouillet P, et al. Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science. 2007;315(5813):856–859.
   PubMed Web of Science ®Google Scholar
• Birkinshaw RW, Gong JN, Luo CS, Lio D, White CA, Anderson MA, Blombery P, Lessene G, Majewski IJ, Thijssen R, et al. Structures of Bcl-2 in complex with venetoclax reveal the molecular basis of resistance mutations. Nat Commun. 2019;10(1):2385.
   PubMed Web of Science ®Google Scholar
• Besbes S, Mirshahi M, Pocard M, Billard C. New dimension in therapeutic targeting of Bcl-2 family proteins. Oncotarget. 2015;6(15):12862–12871.
   PubMed Web of Science ®Google Scholar
• Scheffold A, Jebaraj BMC, Stilgenbauer S. Venetoclax: targeting bcl2 in hematological cancers. Recent Results Cancer Res. 2018; 212:215–242.
   PubMedGoogle Scholar
• Milella M, Estrov Z, Kornblau SM, Carter BZ, Konopleva M, Tari A, Schober WD, Harris D, Leysath CE, Lopez-Berestein G, et al. Synergistic induction of apoptosis by simultaneous disruption of the bcl-2 and MEK/MAPK pathways in acute myelogenous leukemia. Blood. 2002;99(9):3461–3464.
   PubMed Web of Science ®Google Scholar
• Manero F, Gautier F, Gallenne T, Cauquil N, Gree D, Cartron PF, Geneste O, Gree R, Vallette FM, Juin P. The small organic compound HA14-1 prevents Bcl-2 interaction with Bax to sensitize malignant glioma cells to induction of cell death. Cancer Res. 2006;66(5):2757–2764.
   PubMed Web of Science ®Google Scholar
• Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, Dayton BD, Ding H, Enschede SH, Fairbrother WJ, et al. Abt-199, a potent and selective Bcl-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013;19(2):202–208.
   PubMed Web of Science ®Google Scholar
• Sattler M, Liang H, Nettesheim D, Meadows RP, Harlan JE, Eberstadt M, Yoon HS, Shuker SB, Chang BS, Minn AJ, et al. Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis. Science. 1997;275(5302):983–986.
   PubMed Web of Science ®Google Scholar
• Lee EF, Czabotar PE, Smith BJ, Deshayes K, Zobel K, Colman PM, Fairlie WD. Crystal structure of ABT-737 complexed with Bcl-xL: Implications for selectivity of antagonists of the Bcl-2 family. Cell Death Differ. 2007;14(9):1711–1713.
   PubMed Web of Science ®Google Scholar
• Li Y, Zhang J, Gao W, Zhang L, Pan Y, Zhang S, Wang Y. Insights on structural characteristics and ligand binding mechanisms of CDK2. Int J Mol Sci. 2015;16(5):9314–9340.
   PubMed Web of Science ®Google Scholar