Quinazoline-Based Analog of Adenine As an Antidote Against MLL-rearranged Leukemia Cells: Synthesis, Inhibition Assays and Docking Studies

References

• Choudhuri S . From Waddington's epigenetic landscape to small noncoding RNA: some important milestones in the history of epigenetics research. Toxicol. Mech. Methods21(4), 252–274 (2011).
   PubMed Web of Science ®Google Scholar
• Berger SL , KouzaridesT , ShiekhattarR , ShilatifardA. An operational definition of epigenetics. Genes Dev.23(7), 781–783 (2009).
   PubMed Web of Science ®Google Scholar
• Goldberg AD , AllisCD , BernsteinE. Epigenetics: a landscape takes shape. Cell128(4), 635–638 (2007).
   PubMed Web of Science ®Google Scholar
• Arimondo PB , BarberousseA , PontarottiG. The many faces of epigenetics Oxford, December 2017. Epigenetics.14(6), 623–631 (2019).
   PubMed Web of Science ®Google Scholar
• Berger SL , KouzaridesT , ShiekhattarR , ShilatifardA. An operational definition of epigenetics. Genes Dev.23(7), 781–783 (2009).
   PubMed Web of Science ®Google Scholar
• Ballestar E , EstellerM. The epigenetic breakdown of cancer cells: from DNA methylation to histone modifications. In: Epigenetics and Chromatin.JeanteurP ( Ed.). Springer, Heidelberg, Germany, 169–181 (2005).
   Google Scholar
• Martin C , ZhangY. The diverse functions of histone lysine methylation. Nat. Rev. Mol. Cell Biol.6(11), 838–849 (2005).
   PubMed Web of Science ®Google Scholar
• Zhang Y , ReinbergD. Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes Dev.15(18), 2343–2360 (2001).
   PubMed Web of Science ®Google Scholar
• Santos-Rosa H , SchneiderR , BannisterAJet al. Active genes are tri-methylated at K4 of histone H3. Nature419(6905), 407–411 (2002).
   PubMed Web of Science ®Google Scholar
• Greer EL , ShiY. Histone methylation: a dynamic mark in health, disease and inheritance. Nat. Rev. Genet.13(5), 343–357 (2012).
   PubMed Web of Science ®Google Scholar
• Feinberg AP , OshimuraM , BarrettJC. Epigenetic mechanisms in human disease. Cancer Res.62(22), 6784–6787 (2002).
   PubMed Web of Science ®Google Scholar
• Neganova ME , KlochkovSG , AleksandrovaYR , AlievG. Histone modifications in epigenetic regulation of cancer: perspectives and achieved progress. Semin. Cancer Biol.S1044-579X(20), 30176–0 (2020).
   Google Scholar
• Italiano A , SoriaJC , ToulmondeMet al. Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study. Lancet Oncol.19(5), 649–659 (2018).
   PubMed Web of Science ®Google Scholar
• Morschhauser F , TillyH , ChaidosAet al. Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial. Lancet Oncol.21(11), 1433–1442 (2020).
   PubMed Web of Science ®Google Scholar
• Hoy SM . Tazemetostat: first approval. Drugs80(5), 513–521 (2020).
   PubMed Web of Science ®Google Scholar
• Bon C , HalbyL , ArimondoPB. Bisubstrate inhibitors: the promise of a selective and potent chemical inhibition of epigenetic ‘writers.’Epigenomics12(17), 1479–1482 (2020).
   PubMed Web of Science ®Google Scholar
• Chen Y , ZhuWG. Biological function and regulation of histone and non-histone lysine methylation in response to DNA damage. Acta Biochim. Biophys. Sin.48(7), 603–616 (2016).
   Google Scholar
• Bon C , SiY , ArimondoPB. Chapter 4 – targeting DOT1L for mixed-lineage rearranged leukemia. In: Histone Modifications in Therapy.Castelo-BrancoP, JeronimoC ( Eds). Academic Press, MA, USA, 81–99 (2020).
   Google Scholar
• Wu F , NieS , YaoYet al. Small-molecule inhibitor of AF9/ENL-DOT1L/AF4/AFF4 interactions suppresses malignant gene expression and tumor growth. Theranostics11(17), 8172–8184 (2021).
   PubMed Web of Science ®Google Scholar
• Grigsby SM , FriedmanA , ChaseJet al. Elucidating the importance of DOT1L recruitment in MLL-AF9 leukemia and hematopoiesis. Cancers13(4), 642 (2021).
   PubMed Web of Science ®Google Scholar
• Sarno F , NebbiosoA , AltucciL. DOT1L: a key target in normal chromatin remodelling and in mixed-lineage leukaemia treatment. Epigenetics15(5), 439–453 (2020).
   PubMed Web of Science ®Google Scholar
• Bernt KM , ZhuN , SinhaAUet al. MLL-rearranged leukemia Is dependent on aberrant H3K79 methylation by DOT1L. Cancer Cell20(1), 66–78 (2011).
   PubMed Web of Science ®Google Scholar
• Perner F , GadreyJY , XiongYet al. Novel inhibitors of the histone methyltransferase DOT1L show potent antileukemic activity in patient-derived xenografts. Blood136(17), 1983–1988 (2020).
   PubMed Web of Science ®Google Scholar
• Lonetti A , IndioV , LaginestraMAet al. Inhibition of methyltransferase DOT1L sensitizes to sorafenib treatment AML cells irrespective of MLL-rearrangements: a novel therapeutic strategy for pediatric AML. Cancers12(7), 1972 (2020).
   PubMed Web of Science ®Google Scholar
• Daigle SR , OlhavaEJ , TherkelsenCAet al. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell20(1), 53–65 (2011).
   PubMed Web of Science ®Google Scholar
• Bon C , SiY , PernakMet al. Synthesis and biological activity of a cytostatic inhibitor of MLLr leukemia targeting the DOT1L protein. Molecules26(17), 5300 (2021).
   PubMed Web of Science ®Google Scholar
• Shukla N , WetmoreC , O'BrienMMet al. Final report of phase 1 study of the DOT1L inhibitor, pinometostat (EPZ-5676), in children with relapsed or refractory MLL-r acute leukemia. Blood128(22), 2780 (2016).
   Web of Science ®Google Scholar
• Basavapathruni A , OlhavaEJ , DaigleSRet al. Nonclinical pharmacokinetics and metabolism of EPZ-5676, a novel DOT1L histone methyltransferase inhibitor. Biopharm. Drug Dispos.35(4), 237–252 (2014).
   PubMed Web of Science ®Google Scholar
• Stauffer F , WeissA , ScheuflerCet al. New potent DOT1L inhibitors for in vivo evaluation in mouse. ACS Med. Chem. Lett.10(12), 1655–1660 (2019).
   PubMed Web of Science ®Google Scholar
• Chen C , ZhuH , StaufferFet al. Discovery of novel DOT1L inhibitors through a structure-based fragmentation approach. ACS Med. Chem. Lett.7(8), 735–740 (2016).
   PubMed Web of Science ®Google Scholar
• Möbitz H , MachauerR , HolzerPet al. Discovery of potent, selective, and structurally novel DOT1L inhibitors by a fragment linking approach. ACS Med. Chem. Lett.8(3), 338–343 (2017).
   PubMed Web of Science ®Google Scholar
• Gibbons GS , ChakrabortyA , GrigsbySMet al. Identification of DOT1L inhibitors by structure-based virtual screening adapted from a nucleoside-focused library. Eur. J. Med. Chem.189, 112023 (2020).
   PubMed Web of Science ®Google Scholar
• Pasco M , MoumnéR , LecourtT , MicouinL. Stereoselective synthesis of fluorinated 1,3-cis-diaminocyclopentanes. J. Org. Chem.76(12), 5137–5142 (2011).
   PubMed Web of Science ®Google Scholar
• Olhava EJ . Methods of synthesizing substituted purine compounds (US201361799147P 20130315) (2014).
   Google Scholar
• Martínez-Rosell G , GiorginoT , DeFabritiis G. PlayMolecule ProteinPrepare: a web application for protein preparation for molecular dynamics simulations. J. Chem. Inf. Model.57(7), 1511–1516 (2017).
   PubMed Web of Science ®Google Scholar
• Frisch MJ , Head-GordonM , TrucksGWet al. Gaussian 90. Gaussian Inc., PA, USA.
   Google Scholar
• ChemBio3D Ultra 13 Suite, PerkinElmer Inc. USA. https://perkinelmerinformatics.com/products/research/signals-lead-discovery/
   Google Scholar
• Jones G , WillettP , GlenRC , LeachAR , TaylorR. Development and validation of a genetic algorithm for flexible docking11. J. Mol. Biol.267(3), 727–748 (1997).
   PubMed Web of Science ®Google Scholar
• Schrödinger, LLC . The open-source PyMOL Molecular Graphics System 1.7.x. https://pymol.org/2/
   Google Scholar
• Stierand K , RareyM. PoseView – molecular interaction patterns at a glance. J. Cheminformatics2(1), P50 (2010).
   Google Scholar
• Basavapathruni A , OlhavaEJ , DaigleSRet al. Nonclinical pharmacokinetics and metabolism of EPZ-5676, a novel DOT1L histone methyltransferase inhibitor. Biopharm. Drug Dispos.35(4), 237–252 (2014).
   PubMed Web of Science ®Google Scholar
• Campbell CT , HaladynaJN , DrubinDAet al. Mechanisms of pinometostat (EPZ-5676) treatment-emergent resistance in MLL-rearranged leukemia. Mol. Cancer Ther.16(8), 1669–1679 (2017).
   PubMed Web of Science ®Google Scholar
• Daigle SR , OlhavaEJ , TherkelsenCAet al. Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood122(6), 1017–1025 (2013).
   PubMed Web of Science ®Google Scholar
• Basavapathruni A , JinL , DaigleSRet al. Conformational adaptation drives potent, selective and durable inhibition of the human protein methyltransferase DOT1L. Chem. Biol. Drug Des.80(6), 971–980 (2012).
   PubMed Web of Science ®Google Scholar
• Hegde VR , SeleyKL , SchnellerSW , ElderTJJ. 5′-amino-5′-deoxy-5′-noraristeromycin. J. Org. Chem.63(20), 7092–7094 (1998).
   PubMed Web of Science ®Google Scholar
• Olhava EJ , ChesworthR , KuntzKW , RichonVM , PollockRM , DaigleSR. Substituted purine and 7 – deazapurine compounds as modulators of epigenetic enzymes (US20100419661P 20101203) (2012).
   Google Scholar
• Pasco M , MoumnéR , LecourtT , MicouinL. Stereoselective synthesis of fluorinated 1,3-cis-diaminocyclopentanes. J. Org. Chem.76(12), 5137–5142 (2011).
   PubMed Web of Science ®Google Scholar
• Prange KHM , MandoliA , KuznetsovaTet al. MLL-AF9 and MLL-AF4 oncofusion proteins bind a distinct enhancer repertoire and target the RUNX1 program in 11q23 acute myeloid leukemia. Oncogene36(23), 3346–3356 (2017).
   PubMed Web of Science ®Google Scholar
• Jones B , SuH , BhatAet al. The histone H3K79 methyltransferase Dot1L is essential for mammalian development and heterochromatin structure. PLoS Genet.4(9), e1000190 (2008).
   PubMed Web of Science ®Google Scholar