Journal Name: Drug Safety

Journal Name: Drug Safety Article Title: Cancer chemotherapy and cardiac arrhythmias: a review Author names: Tamargo J, Caballero R, Delpón E Author Affiliations: Department of Pharmacology, School of Medicine, University Complutense, Madrid.

Electronic Supplementary Table 1. Classification, mechanism of action and representative chemotherapy drugs

Class Mechanism of action Representative drugs Alkylating Bind covalently to DNA and  Busulfan, Carmustine agents promotes cross-linking of DNA, Cyclophosphamide, abnormal base pairing, or DNA Ifosphamide, Melphalan strand breaks and blockade of  Platinum drugs: DNA replication carboplatin, cisplatin, oxaliplatin Angiogenesis Slow/stop the growth of new Lenalidomide, Thalidomide inhibitors blood vessels which tumour needs to grow and survive Anthracycline Intercale into DNA, inhibits Daunorubicin, Doxorubicin, s topoisomerase II, and prevent Epirubicin, Idarubicin, Antraquinones DNA and RNA synthesis Mitoxantrone

Antimetabolit Block the synthesis of nucleic Capecitabine, Cytarabine, 5- es (Pyrimidine acids required for DNA replication fluorouracil, Fludarabine, analogues) Gemcitabine, Methotrexate, Pentostatin Antitumor Cause DNA alkylation and cross- Bleomycin, Mitomycin, antibiotics linking Cytokines Necessary for the growth, Interleukin-2 proliferation, and differentiation T cells Histone Removal of acetyl groups by Dacinostat, Panibinostat, deacetylase HDAC stabilizes the interaction Romidepsin, Vorinostat (HDAC) between DNA and histones, inhibitors repressing transcription. Microtubule Block cell division by stabilizing  Taxanes: docetacel, targeting GDP-bound tubulin in the paclitaxel agents microtubules. Vinca alkaloids  Vinca alkaloids: destroy mitotic spindles vinblastine, vincristine, vinorelbine  Eribulin mesylate, Ixapepilone Non-specific Interferon, Interleukin-2 immunothera 2 pies Proteasome Binds the catalytic site of the 26S Bortezomib, Carfilzomib inhibitors proteasome Protein kinase Impairs VEGF activity and tumor Enzastaurin Cβ inhibitors angiogenesis Protein kinase  Small molecules interfering  Afatinib, Axitinib, inhibitors with intracellular downstream Bosutinib, Crizotinib, (PKIs) signaling pathways of protein Dasatinib, Erlotinib, Gefitinib, kinase-linked receptors Imatinib, Lapatinib, Nilotinib, Ponatinib, regorafenib, Ruloxitinib, Sorafenib,  Monoclonal antibodies Sunitinib, Vandetanib, directed against specific Vemurafenib membrane bound components  Alemtuzumab, of receptor tyrosine kinases Bevacizumab, Cetuximab, Gentuzumab, Pertuzumab, Rituximab, Trastuzumab Topoisomeras Prevent religation of DNA strands, Amsacrine, Etoposide, e II inhibitors cause DNA strand breaks, and Mitoxantrone lead to apoptosis. Other drugs Causes degradation of the PML- Arsenic trioxide RARα fusion protein in leukemic cells Abbreviations: GDP: guanosine diphosphate. HDAC: histone deacetilase inhibitors. PML/RARα: promyelocytic leukemia/Retinoic acid receptor α. VEGF: vascular endothelial growth factor.