TABLE 1.
Summary of approved selective small molecule kinase inhibitors
| Class | Drug name | Company | First approval | Target | Protein substrate | Administration pathway | Indications |
|---|---|---|---|---|---|---|---|
| ABL | Imatinib (Gleevec) | Novartis | 2001 | BCR–ABL, PDGFR, SCF, KIT | Tyrosine | Oral | Ph‐positive CML, Ph‐positive ALL, PDGFR rearrangements MDS/MPD, ASM, HES, CEL, DFSP, KIT‐positive GIST |
| ABL | Dasatinib (Sprycel) | Bristol‐Myers Squibb | 2006 | BCR–ABL, SRC family (SRC, LCK, YES, FYN), and KIT, EPHA2, PDGFRβ | Tyrosine | Oral | Ph‐positive CML, Ph‐positive ALL, |
| ABL | Nilotinib (Tasigna) | Novartis | 2007 | BCR–ABL, PDGFRB, KIT | Tyrosine | Oral | Ph‐positive CML |
| ABL | Bosutinib (Bosulif) | Wyeth Inc | 2012 | BCR–ABL, SRC‐family (SRC, LYN, and HCK) | Tyrosine | Oral | Ph‐positive CML |
| ABL | Ponatinib (Iclusig) | Ariad | 2012 | BCR–ABL, BCR–ABL (T315I), VEGFR, PDGFR, FGFR, EPH receptors, SRC families of kinases, KIT, RET, TIE2, FLT3 | Tyrosine | Oral | Ph‐positive CML and Ph‐positive ALL resistant/intolerant to therapy, T315I‐positive CML, T315I‐positive/Ph‐positive ALL |
| ABL | Asciminib (Scemblix) | Novartis | 2021 | BCR–ABL, BCR–ABL (T315I) | Tyrosine | Oral | Ph‐positive CML‐CP resistant to therapy, T315I‐positive CML |
| KIT | Ripretinib (Quinlock) | Deciphera | 2020 | KIT, PDGFRA, PDGFRA mutations, PDGFRB, TIE2, VEGFR2, BRAF | Tyrosine | Oral | GIST |
| KIT | Avapritinib (Ayvakit) | Blueprint Medicines | 2020 | KIT, KIT D816V, KIT exon 11, 11/17, and 17 mutants, PDGFRA and PDGFRA D842 mutants, PDGFRB, and CSFR1 | Tyrosine | Oral | PDGFRA exon 18 mutation (including D842V) positive GIST, advanced systemic mastocytosis |
| HER | Gefitinib (Iressa) | AstraZeneca | 2003 | EGFR and HER family | Tyrosine | Oral | NSCLC |
| HER | Erlotinib (Tarceva) | OSI | 2004 | EGFR and HER family | Tyrosine | Oral | NSCLC with EGFR 19del or L858R, pancreatic cancer |
| HER | Afatinib (Gilotrif) | Boehringer Ingelheim | 2013 | EGFR and HER family | Tyrosine | Oral | NSCLC with nonresistant EGFR mutations, squamous NSCLC |
| HER | Osimertinib (Tagrisso) | AstraZeneca | 2015 | EGFR and HER family | Tyrosine | Oral | NSCLC with EGFR 19del or L858R, NSCLC with T790M positive |
| HER | Dacomitinib (Vizimpro) | Pfizer | 2018 | EGFR and HER family | Tyrosine | Oral | NSCLC with EGFR 19del or L858R |
| HER | Mobocertinib (Exkivity) | Takeda Pharmaceuticals | 2021 | EGFR and HER family | Tyrosine | Oral | NSCLC with EGFR 20 exon insertion |
| HER | Lapatinib (Tykerb) | SmithKline Beecham | 2007 | EGFR and HER family | Tyrosine | Oral | HER2‐positive breast cancer |
| HER | Neratinib (Nerlynx) | Puma Biotechnology | 2017 | EGFR and HER family | Tyrosine | Oral | HER2‐positive breast cancer |
| HER | Tucatinib (Tukysa) | Seattle Genetics | 2020 | EGFR and HER family | Tyrosine | Oral | HER2‐positive breast cancer |
| ALK | Crizotinib (Xalkori) | PF Prism CV | 2011 | ALK, HGFR, c‐Met, ROS1, RON | Tyrosine | Oral | ALK‐ or ROS1‐positive NSCLC, ALK‐positive anaplastic large cell lymphoma |
| ALK | Ceritinib (Zykadia) | Novartis | 2014 | ALK, IGF‐1R, InsR, ROS1 | Tyrosine | Oral | ALK‐positive NSCLC |
| ALK | Alectinib (Alecensa) | Roche | 2015 | ALK, RET | Tyrosine | Oral | ALK‐positive NSCLC |
| ALK | Brigatinib (Alunbrig) | ARIAD | 2017 | ALK, ROS1, IGF‐1R, FLT‐3, EGFR deletion and point mutations | Tyrosine | Oral | ALK‐positive NSCLC |
| ALK | Lorlatinib (Lorviqua) | Pfizer | 2018 | ALK, ROS1, TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2, ACK | Tyrosine | Oral | ALK‐positive NSCLC |
| MET | Capmatinib (Tabrecta) | Novartis | 2020 | MET, MET exon 14 skipping | Tyrosine | Oral | NSCLC with MET exon 14 skipping |
| MET | Tepotinib (Tepmetko) | Merck | 2021 | MET, MET exon 14 skipping | Tyrosine | Oral | NSCLC with MET exon 14 skipping |
| RET | Pralsetinib (Gavreto) | Blueprint Medicines | 2020 | wild‐type RET, oncogenic RET fusions (CCDC6‐RET), RET mutations (RET V804L, RET V804M and RET M918T) | Tyrosine | Oral | RET fusion‐positive NSCLC, RET mutant MTC, RET fusion‐positive thyroid cancer |
| RET | Selpercatinib (Retevmo) | Eli Lilly | 2020 | wild‐type RET, multiple mutated RET isoforms | Tyrosine | Oral | RET fusion‐positive NSCLC, RET mutant MTC, RET fusion‐positive thyroid cancer |
| FGFR | Erdafitinib (Balversa) | Janssen | 2019 | FGFR1, FGFR2, FGFR3, FGFR4, RET, CSF1R, PDGFRA, PDGFRB, FLT4, KIT, VEGFR2 | Tyrosine | Oral | Urothelial carcinoma with FGFR3 or FGFR2 genetic alterations |
| FGFR | Pemigatinib (Pemazyre) | Incyte | 2020 | FGFR1, FGFR2, FGFR3 | Tyrosine | Oral | Cholangiocarcinoma with FGFR2 fusion or other rearrangement |
| FGFR | Infigratinib (Truseltiq) | Helsinn Hlthcare | 2021 | FGFR1, FGFR2, FGFR3, FGFR4 | Tyrosine | Oral | Cholangiocarcinoma with FGFR2 fusion or other rearrangement |
| TRK | Larotrectinib (Vitrakvi) | Loxo Oncology | 2018 | NTRK1, NTRK2, NTRK3 | Tyrosine | Oral | NTRK fusion‐positive tumours |
| TRK | Entrectinib (Rozlytrek) | Genentech | 2019 | NTRK1, NTRK2, NTRK3, ROS1, ALK, JAK2, TNK2 | Tyrosine | Oral | NTRK fusion‐positive tumours, ROS1 positive NSCLC |
| FLT3 | Midostaurin (Rydapt) | Novartis | 2017 | FLT3 | Tyrosine | Oral | FLT mutant AML, ASM, SM‐AHN, MCL |
| FLT3 | Gilteritinib (Xospata) | Astellas | 2018 | FLT3 | Tyrosine | Oral | FLT mutant AML |
| CSF1R | Pexidartinib (Turalio) | Daiichi Sankyo | 2019 | CSF1R, KIT, FLT3 with ITD mutation | Tyrosine | Oral | Tenosynovial giant cell tumor |
| RAF | Vemurafenib (Zelboraf) | Hoffmann La Roche | 2011 | mutated forms of BRAF, wild‐type BRAFCRAF, ARAF, SRMS, ACK1, MAP4K5, FGR | Serine‐threonine | Oral | Melanoma with BRAF V600E |
| RAF | Dabrafenib (Tafinlar) | GSK | 2013 | BRAF V600E, BRAF V600K, and BRAF V600D, wild‐type BRAF, CRAF, SIK1, NEK11, LIMK1 | Serine‐threonine | Oral | Melanoma with BRAF V600E, in combination with trametinib: melanoma with BRAF V600E or V600K, NSCLC with BRAF V600E, ATC with BRAF V600E, solid tumors with BRAF V600E |
| RAF | Encorafenib (Braftovi) | Array BioPharma | 2018 | BRAF V600E, wild‐type BRAF, CRAF, JNK1, JNK2, JNK3, LIMK1, LIMK2, MEK4, STK36 | Serine‐threonine | Oral | In combination with binimetinib: melanoma with BRAF V600E or V600K, in combination with cetuximab: CRC with BRAF V600E |
| MEK | Trametinib (Mekinist) | GSK | 2013 | MEK1, MEK2 | Serine‐threonine | Oral | Melanoma with BRAF V600E or V600K, in combination with dabrafenib: melanoma with BRAF V600E or V600K, NSCLC with BRAF V600E, ATC with BRAF V600E, solid tumors with BRAF V600E |
| MEK | Cobimetinib (Cotellic) | Genentech/Exelixis | 2015 | MEK1, MEK2 | Serine‐threonine | Oral | In combination with vemurafenib: melanoma with a BRAF V600E or V600K |
| MEK | Binimetinib (Mektovi) | Array BioPharma | 2018 | MEK1, MEK2 | Serine‐threonine | Oral | In combination with encorafenib: melanoma with a BRAF V600E or V600K |
| MEK | Selumetinib (Koselugo) | Astra Zeneca | 2020 | MEK1, MEK2 | Serine‐threonine | Oral | Neurofibromatosis type 1 |
| PI3K | Idelalisib (Zydelig) | Gilead Sciences | 2014 | PI3Kδ | Phosphatidylinosi‐tol 3‐kinase | Oral | CLL |
| PI3K | Copanlisib (Aliqopa) | Bayer Healthcare | 2017 | PI3Kα, PI3Kδ | Phosphatidylinosi‐tol 3‐kinase | Intravenous | FL |
| PI3K | Duvelisib (Copiktra) | Secura | 2018 | PI3Kδ, PI3Kγ | Phosphatidylinosi‐tol 3‐kinase | Oral | CLL/SLL |
| PI3K | Alpelisib (Piqray) | Novartis | 2019 | PI3Kα | Phosphatidylinosi‐tol 3‐kinase | Oral | HR‐positive, HER2‐negative breast cancer, PIK3CA‐mutated breast cancer (in combination with fulvestrant) |
| PI3K | Umbralisib (Ukoniq) | TG Theraps | 2021 | PI3Kδ, CK1ε | Phosphatidylinosi‐tol 3‐kinase | Oral | MZL, FL |
| JAK | Ruxolitinib (Jakafi) | Incyte | 2011 | JAK1, JAK2 | Tyrosine | Oral | Myeloproliferative neoplasms |
| JAK | Fedratinib (Impact) | Impact | 2019 | JAK2 | Tyrosine | Oral | Myeloproliferative neoplasms |
| CYC | Palbociclib (Ibrance) | Pfizer | 2015 | CDK4, CDK6 | Serine‐threonine | Oral | HR‐positive, HER2‐negative breast cancer |
| CYC | Ribociclib (Kisqali) | Novartis | 2017 | CDK4, CDK6 | Serine‐threonine | Oral | HR‐positive, HER2‐negative breast cancer |
| CYC | Abemaciclib (Verzenio) | Eli Lilly | 2017 | CDK4, CDK6 | Serine‐threonine | Oral | HR‐positive, HER2‐negative breast Cancer |
| CYC | Trilaciclib (Cosela) | G1 Therap | 2021 | CDK4, CDK6 | Serine‐threonine | Intravenous | Prevent chemotherapy‐induced myelosuppression in SCLC |
| BTK | Ibrutinib (Imbruvica) | Sandoz | 2013 | BTK | Tyrosine | Oral | MCL, CLL/SLL, CLL/SLL with 17p deletion, WM, MZL |
| BTK | Acalabrutinib (Calquence) | AstraZeneca | 2017 | BTK | Tyrosine | Oral | MCL, CLL/SLL |
| BTK | Zanubrutinib (Brukinsa) | BeiGene | 2019 | BTK | Tyrosine | Oral | MCL, WM, MZL |
| IDH1 and IDH2 | Enasidenib (Idhifa) | CelGene | 2017 | IDH1 and IDH2 | Tyrosine | Oral | IDH2 mutant AML |
| IDH1 and IDH2 | Ivosidenib (Tibsovo) | Servier | 2018 | IDH1 and IDH2 | Tyrosine | Oral | IDH1 mutant AML, IDH1 mutant cholangiocarcinoma |
| SRC | Tirbanibulin (Klisyri) | Almirall | 2020 | SRC | Tyrosine | Opical | Actinic keratosis |
Abbreviations: Ph‐positive CML, Philadelphia chromosome‐positive chronic myeloid leukemia; Ph‐positive ALL, Philadelphia chromosome positive acute lymphoblastic leukemia; MDS/MPD, myelodysplastic/myeloproliferative diseases; ASM, aggressive systemic mastocytosis; HES, hypereosinophilic syndrome; CEL, chronic eosinophilic leukemia; DFSP, dermatofibrosarcoma protuberans; GIST, gastrointestinal stromal tumors; NSCLC, nonsmall cell lung cancer; MTC, medullary thyroid cancer; AML, acute myeloid leukemia; SM‐AHN, systemic mastocytosis with associated hematological neoplasm; MCL, mantle cell lymphoma; CRC, colorectal cancer; ATC, anaplastic thyroid cancer; CLL/SLL, chronic lymphocytic leukemia/small lymphocytic lymphoma; FL, follicular lymphoma; MZL, marginal zone lymphoma; MCL, mantle cell lymphoma; WM, waldenström's macroglobulinemia. Data sources: https://www.fda.gov/drugs/development‐approval‐process‐drugs/drug‐approvals‐and‐databases.