References
Indenos and Azas Overview
Cushman M. Design and Synthesis of Indenoisoquinoline Topoisomerase I Inhibitors for Cancer Chemotherapy. J. Med. Chem. 2021, 64, 24, 17572–17600.
C-MYC Promoter G-Quadruplex Regulation
Bacolla A, Z Ye, Z Ahmed, J Tainer. Cancer mutational burden is shaped by G4 DNA, replication stress, and mitochondrial dysfunction. Prog Biophys Mol Biol. DOI: 10.1016/jbiomolbio.2019.03.004-0079-6107
Hui WWI, A Simeone, KG Zyner et al. Single-cell mapping of DNAG-quadruplex structures in human cancer cells. Nature (2021) 11:23641. DOI.org/10.1038/s41598-021-02943-3.
Kim N. The Interplay between G-quadruplex and Transcription. Cur Medicinal Chem 2019,26,2898-2917. DOI: 10.2174/0929867325666171229132619.
Kosiol N, S Juranek, P Brossart erttr al. G-quadruplexes: a promising target for cancer therapy. Mol Cancer (2021) 20-40. DOI: 10.1186/s12943-021-01328-4.
Neidle S, A Ahmed, R Angell, S Oxenford. The potent quadruplex-binding compound QN-302 shows anti-tumor activity in patient-derived in vivo models of pancreatic cancer. AACR Abstract 4069. April 2022. (Qualigen)
Paul R, T Das, M Debnath, et al. G-Quadruplex-Binding Small Molecule Induces Synthetic Lethality in Breast Cancer Cells by Inhibiting c-MYC and BCL2 Expression. ChemBioChem 2019,20,1-9. Doi: 10.1002/cbic.201900534.
Psaras AM, S Valiuska, V Noe et al. Facilitating G-quadruplex formation in the KRAS promoter with polypurine reverse Hoogsteen oligonucleotides. Can Res Abstract 675 (2022)82 (12_Supplement);675.
Siddiqui-Jain, CL Grand, DJ Bearss et al. Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription. PNAS (2002) 99(18) 11593-11598. DOI: 10.1073/pnas.182256799
Kiselev E, K Agama, Y Pommier, MCushman. Azaindenoisoquinolines as Topoisomerase I Inhibitors and Potential Anticancer Agents: A Systematic Study of Structure-Acftivity Relationships. J Med Chem 2012,55,1682-1697.
Thomas A and Y Pommier. Targeting Topoisomerase I in the Era of Precision Medicine. Clin Cancer Res. 2019,15:25(22):6581-6589. Doi://10.1158/1078-0432,CC%-19—1089.
7-Azas and Indenos in G-quadruplex C-Myc Inhibition
Beck DE, PVN Reddy, Y Pommier, M Cushman et al. Investigation of the Structure-Activity Relationships of Aza-A-Ring Indenoisoquinoline TopisomerSE I Poisons. J Med Chem 2016, 59,8,3840-3853.
Berroyer A, A Bacolla, J Tainer, N Kim. Cleavage-defective Topoisomerase I mutants sharply increase G-quadruplex-associated genomic instability. Microb Cell 2022; 9(3):52-68. DOI: 10.15698/mic2022.03.771.
Cushman M, D Nagarathnam, D Gopal, H M He, C M Lin, E Hamel. Synthesis and evaluation of analogs of (Z)-1-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethene as potential cytotoxic and antimitotic agents. J Med Chem 1992,35,12,2293-2306.
Elsayed SA, Y Su, P Wang, MY Pommier, M Cushman et al. Design and Synthesis of Chlorinated and Fluorinated 7-Azaindenoisoquinolines as Potent Cytotoxic Anticancer Agents that Inhibit Topoisomerase 1. J Med Chem 2017,60,13,5364-5376.
Kiselev E, T Dexheimer, Y Pommier, M Cushman. Design, Synthesis, and Evaluation of Dibenzo(c,h) (1,6) napthyridines as Topoisomerase I Inhibitors ND Potential Anticancer Agents. J Med Chem 2010,53,24,8716-8726.
Kiselev, S Deguire, Y Pommier, M Cushman et al. 7-Azaindenoisoquinolines as Topoisomerase I Inhibitors and Potential Anticancer Agents. J Med Chem 2011, 54:6106-6116. Doi: 10.1021/jm200719v.
Kiselev E, D Sooryakumar, K Agama, M Cushman, Y Pommier. Optimization of the Lactam Side Chair of 7-Azaindenoisoquinoline Topoisomerase I Inhibitors and Mechanism of Action Studies in Cancer Cells. J Med Chem 2014; 57:1289-1298. Doi: 10.1021/jm40147v1.
Liu W, C Lin, D Yang et al. Structures of 1:1 and 2:1 complexes of BMVC and MYC promoter G-quadruplex reveal a mechanism of ligand conformation adjustment for G4-recognition.
Wang P, MSA Elsayed, Y Pommier, M Cushman et al. Synthesis and Biological Evaluation of the First Triple Inhibitors of Human Topoisomerase 1, Tyrosyl-DNA Phosphodiesterase 1 (Tdpd1), and Tyrosyl-DNA Phosphodiesterase 2 (tdp2). J Med Chem 2017, 60,8,3275-3288.
Wang KB, D Yang, M Cushman, et al. Indenoisoquinoline Topoisomerase Inhibitors Strongly Bind and Stabilize the MYC Promoter G-Quadruplex and Downregulate MYC. J Am. Chem. Soc. 2019, 141, 28, 11059-11070. DOI: 10.1021/jacs.9b02679
Indenos work when Irinotecan Resistance
Jandu H, K Aluzaite, L Fogh, et al. Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines.
BMC Cancer (2016) 16:34.
DOI 10.1186/s 12885-016-2071-1
Veterinary Clinical Trials
Clinical Studies
Schlafen 11 (SLFN11) Biomarkers
Murai J and Y Pommier. Abstract 5875: Schlafen 11 (SLFN11) induces lethal S-phase arrest in response to DNA damage: A novel mechanism of how cancer cells are killed by DNA damaging agents. AACR 2017. DOI: 10.1158/1538-7445.AM2017-5975.
Murai J, SW Tang, E Leo…Y Pommier . SLFN11 Blocks Stress Replication Forks Independently of ATR. J Mol Cell 2018; 69(3):371-384.
Pommier Y, L Marzi, ZW Ohler..M Cushman et al. Abstract 4855: Indotecan (LMP400), Imidotecan (LMP776) and LMP744: a new class of non-camptothecin TOP1 inhibitors selective for cancer cells with homologous recombination deficiencies and high SLFN11 expression. 2018 Proceedings AACR . DOI: 10.1158-7445.AM2018-4855.
Glioblastoma and Pontine Gliomas
Fatma H, S Maurya, H Siddique. Epigenetic modifications of c-MYC: Role in cancer cell reprogramming, progression and chemoresistance. Sem in Cancer Biol (2022) 83,166-176. https://doi.org/10.1016/j.semcancer.2020.11.008