Table1: Small moleculeTable 1: Small molecule inhibitors of protein kinases approved for clinical use or in late Phase 3 clinical trials.

Reported Approved for clinical Reported Approved for clinical Reported Approved for clinical Name Structure Company Name Structure Company Name Structure Company target use target use target use

2012 1995 Bcr-Abl chronic PI3K 2017 Fasudil (Eril) ROCK1/2 Asahi Kasei cerebral vasospasm Bosutinib Pfizer Copanlisib Bayer SRC myelogenous mTOR follicular lymphoma PAH leukemia

2012 1999 Sirolimus Wyeth Bcr-Abl chronic 2017 mTOR kidney Radotinib Daewoong Netarsudil ROCK Aerie (Rapamune) Pfizer PDGFR myelogenous glaucoma (topical) transplantation leukemia

2001 Bcr-Abl chronic 2013 EUSA 2017 Imatinib c-KIT Novartis Dabrafenib BRAF GSK Tivozanib VEGFR myelogenous skin cancer Pharma RCC PDGFR leukemia

Bruton's AZ 2017 2003 2013 Gefitinib EGFR AZ Trametinib MEK1/2 GSK Acalabrutinib Tyrosine Acerta mantle cell NSCLC skin cancer Kinase Pharma lymphoma, CLL

2004 2013 2018 Genetech Her2 Erlotinib EGFR NSCLC Afatinib BI NSCLC with EGFR Fostamatinib SYK Rigel autoimmune Roche EGFR pancreatic cancer mutations thrombocyto-penia

Multiple 2005 Bruton's Janssen 2013 Jiangsu Tyrosine Onyx 2018 Sorafenib renal cancer Ibrutinib Tyrosine Pharmacycl mantle cell Simotinib EGFR Simcere kinases Bayer NSCLC HCC Kinase ic lymphoma, CLL Pharm. targeted 2006 Multiple renal cancer, 2014 Tyrosine- Sugen MEK ARRAY 2018 Sunitinib Imatinib resistant Ripasudil ROCK Kowa glaucoma Encorafenib kinases Pfizer RAF Novartis melanoma Gastro-Intestinal ocular hypertension targeted Stromal Tumour 2014 EGFR 2007 ARRAY 2018 Lapatinib GSK Ceritinib ALK Novartis NSCLC with Binimetinib MEK RAF ERBB2 breast cancer Novartis melanoma ALK translocations

Multiple 2007 Gilead, 2014 2018 Tyrosine- chronic Infinity Dasatinib BMS Idelalisib PI3K δ Calistoga, chronic lymphocytic Duvelisib PI3K δ/ γ CLL kinases myelogenous Verastem ICOS leukemia, FL SLL targeted leukemia , ALL

2007 VEGFR 2014 2018 chronic Nilotinib Bcr-Abl Novartis Nintedanib PDGFR BI idiopathic Dacomitinib EGFR Pfizer NSCLC with EGFR myelogenous FGFR pulmonary fibrosis mutations leukemia

2014 2018 2009 Roche, Everolimus mTOR Novartis Alectinib ALK NSCLC with ALK Gilteritinib FLT3 AXL Astellas acute myeloid renal cell carcinoma Chugai translocations leukemia

2015 2009 2018 Wyeth advanced LOXO Temsirolimus mTOR advanced renal Palbociclib CDK4/6 Pfizer Larotrectinib NTRK cancer with NTRK Pfizer (metastatic) breast Bayer cell carcinoma fusions cancer

2015 VEGFR2 2009 thyroid cancer ALK Pazopanib PDGFR GSK Lenvatinib VEGFRs Eisai Lorlatinib Pfizer 2018 NSCLC renal cancer (DTC), kidney ROS c-KIT cancer

2011 ALK Roche, 2015 Astex 2019 Crizotinib Pfizer NSCLC with Cobimetinib MEK Erdafitinib FGFR MET Exelixis melanoma Janssen urothelial cancer Alk mutation

Multiple 2015 Tyrosine 2011 2019 Vandetanib AZ Osimertinib EGFR AZ NSCLC with EGFR Alpelisib PI3Kα Novartis kinases thyroid cancer breast cancer mutation targeted

2016 Incyte 2011 CSF1R 2019 Ruxolitinib JAKs Olmutinib EGFR BI NSCLC with EGFR Pexidartinib Plexxikon Novartis myelofibrosis c-KIT TGCT mutation

2011 2017 TRK Roche metastatic advanced Ignyta 2019 Vemurafenib BRAF Ribociclib CDK4/6 Novartis Entrectinib ROS Plexxikon melanoma (metastatic) breast Roche NSCLC ALK BRAFV600E cancer

VEGFRs 2017 2011 2019 Axitinib PDGFRB c- Pfizer Brigatinib ALK EGFR Ariad NSCLC with EGFR Upadacitinib JAK AbbVie renal cell carcinoma rheumatoid arthritis KIT mutation

2017 VEGFR2 2012 acute myeloid 2019 Regorafenib TIE2 others Bayer colorectal cancer Midostaurin FLT3 KIT Novartis Fedratinib JAK Celgene leukemia myelofibrosis PTKs GIST, HCC mastocytosis

2017 2019 2012 Wyeth TG Tofacitinib JAKs Pfizer Neratinib EGFR breast cancer Umbralisib PI3Kδ marginal zone rheumatoid arthritis Pfizer Therapeutic HER2 lymphoma

2012 Bruton's 2019 VEGFR2 Incyte 2017 Cabozantinib Exelixis medullary Baricitinib JAKs Zanubrutinib Tyrosine Beigene mantle cell PDGFR KIT Eli Lilly rheumatoid arthritis thyroid cancer Kinase lymphoma

2012 2017 2020 SRC chronic advanced PDGFR Ponatinib Ariad Abemaciclib CDK4/6 Eli Lilly Avapritinib Blueprint Gastro-Intestinal Abl myelogenous (metastatic) breast KIT Stromal Tumour leukemia, ALL cancer