Table 1.
Approved kinase inhibitors as of February 2015
| Generic name (compound code, trade names) | Kinase target | Disease | Company (year, type) |
|---|---|---|---|
| Fasudil (HA-1077) | ROCK1/2 | Cerebral vasospam, PAH | Asahi Kasei (1995, type-1) |
| Sirolimus (Rapamune) | mTOR | Kidney transplants | Pfizer, Wyeth (1999, type-3) |
| Imatinib (STI571, Glivec, Gleevec) | ABL, PDGFR, KIT | CML, Ph+ B-ALL, CMML, HES, GIST | Novartis (2001, type-2) |
| Gefitinib (ZD1839, Iressa) | EGFR | NSCLC | AZ (2003, type-1) |
| Erlotinib (OSI-774,Tarceva) | EGFR | NSCLC, pancreatic cancer | Roche, OSI (2004, type-1) |
| Sorafenib (BAY 43-9006, Nexavar) | VEGFR2, PDGFR, KIT, FLT3, BRAF | RCC, HCC | Bayer, Onyx (2005, type-2) |
| Sunitinib (SU11248, Sutent) | VEGFR, KIT, PDGFR, RET, CSF1R, FLT3 | RCC, imatinib resistant GIST | Pfizer (2006, type-1) |
| Lapatinib (GW2016, Tykerb) | EGFR, ERBB2 | BC | GSK (2007, type-1.5) |
| Dasatinib (BM-354825,Sprycel) | ABL], PDGFR, KIT, SRC | CML | BMS (2007, type-1) |
| Nilotinib (AMN107,Tasigna) | ABL, PDGFR, KIT | CML | Novartis (2007, type-2) |
| Everolimus (Rad001, Certican, Zortress, Afinitor, Votubia) | mTOR | RCC, SEGA, Transplantation | Novartis (2009, type-3) |
| Temsirolimus (CCI-779, Torisel) | mTOR | RCC | Pfizer, Wyeth (2009, type-3) |
| Crizotinib (PF-02341066, Xalcori) | MET and ALK | NSCLC with ALK translocations | Pfizer (2011, type-1) |
| Vandetanib (ZD6474, Caprelsa) | RET, VEGFR1-2, FGFR, EGFR | MTC | AZ (2011, type-1) |
| Ruxolitinib (INC424, Jakafi) | JAK2 | IMF with JAK2V617F mutations | Novartis, Incyte (2011, type-1) |
| Vemurafenib (PLX4032, RG7204, Zelboraf) | BRAF | Metastatic melanoma with BRAFV600E mutations | Roche, Plexxikon (2011, type-2) |
| Axitinib (AG013736, Inlyta) | VEGFR, KIT, PDGFR, RET, CSF1R, FLT3 | RCC | Pfizer (2012, type-1) |
| Regorafenib (BAY 73-4506, Stivarga) | VEGFR2, Tie2 | CRC, GIST | Bayer (2012, type-2) |
| Pazopanib (GW-786034, Votrient) | VEGFR, PDGFR, KIT | RCC | GSK (2012, type-1) |
| Tofacitinib (CP-690550, Xeljanz Tasocitinib) | JAK3 | RA | Pfizer (2012, type-1) |
| Cabozantinib (XL184, BMS907351, Cometriq) | VEGFR2, PDGFR, KIT, FLT3 | MTC | Exelexis (2012, type-1) |
| Ponatinib (AP24534, Iclusig) | ABL | Imatinib resistant CML with T315I mutations | Ariad (2012, type-1) |
| Bosutinib (SKI-606, Bosulif) | ABL | CML resistant/ intolerant to therapy | Pfizer (2012, type-1) |
| Dabrafenib (Tafinlar) [6494] | BRAF | Metastatic melanoma with BRAFV600E mutations | GSK (2013, type-2) |
| Trametinib (Mekinist) [6495] | MEK | Metastatic melanoma with BRAFV600E mutations | GSK (2013, type-3) |
| Afatnib (Gilotrif, Tomtovok, Tovok) | EGFR | NSCLC with EGFR activating mutations | BI (2013, covalent) |
| Ibrutinib (PCI-32765, Imbruvica) | BTK | MCL, CLL | Janssen, Pharmacyclic (2013, covalent) |
| Ceritinib (LDK378, Zykadia) | ALK | NSCLC with ALK translocations | Novartis (2014, type-1) |
| Idelalisib (CAL101, GS1101, Zydelig) | PI3Kdelta | CLL, FL and SLL | Gilead, Calistoga, ICOS (2014, type-1) |
| Nintedanib (BIBF 1120, Vargatef, Intedanib) | VEGFR, PDGFR, FGFR | Idiopathic Pulmonary Fibrosis | BI (2014, type-1) |
| Alectinib (AF802, RO5424802) | ALK | ALK-rearranged NSCLC | Roche (2014) |
| Palbociclib (PD-0332991, Ibrance) | CDK4/6 | Advanced (metastatic) BC | Pfizer (2015) |
| Lenvatinib (E7080) | VEGFRs | Thyroid cancer | Eisai Co (2015) |
The biochemical profiles of the 33 approved kinase inhibitors are stored in the IUPHAR database (http://www.guidetopharmacology.org/GRAC/LigandListForward?type=Approved&database=all). The 33 kinase inhibitors approved to date are shown with generic compound name, compound code, trade name, primary indications, company and mode of binding. The approved kinase inhibitors include fasudil (HA-1077) (Shibuya and Suzuki, 1993; Shibuya et al., 2001), sirolimus (Rapamycin, Rapamune®) (Kelly et al., 1997; Vasquez, 2000), imatinib (Glivec®) (Druker et al., 1996), gefitinib (Iressa™ ) (Barker et al., 2001), erlotinib (Tarceva™) (Perez-Soler, 2004), lapatinib (Tykerb®) (Gaul et al., 2003), sorafenib (Nexavar®) (Lowinger et al., 2002), sunitinib (Sutent®) (Sun et al., 2003), dasatinib (Sprycel®) (Lombardo et al., 2004), nilotinib (Tasigna®) (Weisberg et al., 2005), torisel (Temsirolimus®) (Galanis et al., 2005), everolimus (Rad001) as Afinitor® (Chan et al., 2010; Baselga et al., 2012; Beck et al., 2014) as Zortress® and Certican™ (Cibrik et al., 2013) as Votubia® for SEGA (Krueger et al., 2010), crizotinib (Xalcori®) (Shaw et al., 2011), vandetanib (Caprelsa®) (Carlomagno and Santoro, 2004; Chau and Haddad, 2013), ruxolitinib (Jakafi®) (Harrison et al., 2012), vemurafenib (Zelboraf®) (Flaherty et al., 2010), axitinib (Inlyta®) (Ansari et al., 2013; Rini et al., 2013), regorafenib (Stivarga®) (Shahda and Saif, 2013), pazopanib (Votrient™) (Sternberg, 2009), tofacitinib (Xeljanz) (Simmons, 2013), cabozantinib (Cometriq) (Viola et al., 2013), ponatinib (Iclusig®) (Nicolini et al., 2013), bosutinib (Bosulif®) (Amsberg and Koschmieder, 2013), dabrafenib (Tafinlar®) (Ballantyne and Garnock-Jones, 2013; King et al., 2013), trametinib (Mekinist®) (Salama and Kim, 2013; Wright and McCormack, 2013), afatinib (Gilotrif®) (Nelson et al., 2013; Ninomiya et al., 2013), ibrutinib (Imbruvica®) (McDermott and Jimeno, 2014), ceritinib (Zykadia®) (Friboulet et al., 2014), idelalisib (Zydelig®) (Gopal et al., 2014) and nintedanib (Vargatef®, Ofev™) (Reck et al., 2014; Richeldi et al., 2014), alectinib (Yang, 2013), palbociclib (Ibrance®) (http://www.onclive.com/web-exclusives/FDA-Approves-Palbociclib-for-Metastatic-Breast-Cancer) and levantinib (http://www.eisai.com/news/enews201407pdf.pdf). All compounds are commercially available. AZ, Astra-Zeneca; BI, Boehringer-Ingelheim; GSK, Glaxo-Wellcome.
CLL, chronic lymphocytic leukaemia; CML, chronic myeloid leukaemia; CMML, chronic myeloid monocytic leukaemia; CSF1R, colony stimulating factor 1 receptor; FL, folliclular lymphoma; HCC, hepatocellular cancer; IMF, idiopathic myelofibrosis; MCL, mantle cell lymphoma; MTC, medullary thyroid cancer; NSCLC, non-small-cell lung cancer; PAH, pulmonary arterial hypertension; RCC, renal cell carcinoma.