Table 1.
Tyrosine Kinase Inhibitors and their association with ABC drug transporters.
| Inhibitor | Tyrosine Kinase Target | Neoplasm(s) Targeted | Clinical Status | Association with ABC Transporters |
|---|---|---|---|---|
| Imatinib (Gleevec, Glivec) | BCR-ABL, c-KIT and PDGFR | CML and ALL, MDS/MPD, ASM HES, CEL, DFSP and GIST | Approved, 2001 | ABCB1 [122], ABCC1 [122], ABCG2 [121] and ABCC10 [123] |
| Nilotinib (Tasigna) | BCR-ABL | CML | Approved, 2007 | ABCB1 [93], ABCG2 [93] and ABCC10 [123] |
| Dasatinib (Sprycel) | BCR-ABL and Src | CML, ALL | Approved, 2006 | ABCB1 [117] and ABCG2 [128] |
| Gefitinib (Iressa) | EGFR | NSCLC | Approved, 2006 | ABCB1 [134] and ABCG2 [133] |
| Erlotinib (Tarceva) | EGFR andHER2 | NSCLC | Approved, 2004 | ABCB1, ABCG2 and ABCC10 [50,72] |
| Lapatinib (Tyverb) | EGFR, HER2 | HER2-positive breast cancer | Approved, 2007 | ABCB1, ABCG2 [137] and ABCC10 [72] |
| Canertinib (CI- 1033) | EGFR, HER2 and ErbB- 4 | Metastatic breast cancer. | Phase II | ABCB1 [108] and ABCG2 [139] |
| Icotinib | EGFR | NSCLC | Approved in china, 2011 | ABCG2 [141] |
| AST1306 | EGFRandHER2 | Solid tumors | Phase I | ABCG2 [131] |
| Sorafenib (BAY 43-9006) | VEGFR, EGFR | Renal and pancreatic cancer | Phase II | ABCC10 and ABCC11 [146] |
| Motesanib | PDGFR, VEGFR and c-KIT | NSCLC, GIST, breast cancer. | Phase III | ABCB1 and ABCG2 [147] |
| Sunitinib (Sutent) | FLT3, PDGFR, VEGFR and c-KIT | RCC, GIST | Approved, 2006 | ABCB1 and ABCG2 [96,143] |
| Telatinib | VEGFR-2, VEGFR-3 PDGFR-β and cKIT | Colorectal and gastric cancer | Phase II/III | ABCG2 [142] |
| Masitinib | c-Kit ,PDGFR α, β | Metastatic gastrointestinal stromal tumors | Phase II/III | ABCG2 and ABCC10 [148,149] |
| Linsitinib | IGF-1R/IR | Adrenocortical carcinoma | Phase III | ABCG2 and ABCC10 [150] |
| Ponatinib | FGFR1-4, FLT3 and PDGFR | CML and Ph+ ALL | Approved, 2012/suspended for vascular clots 2013 | ABCB1, ABCG2 [129] and ABCC10 [130] |
| PD173074 | FGFR | NSCLC | Phase I | ABCB1 [151] and ABCC10 [152] |
| Vemurafenib | B-Raf/MEK/ERK | Melanona | Approved, 2011 | ABCB1, ABCG2 and ABCC10 [154] |
BCR-ABL: Breakpoint cluster region-Abelson complex; c-KIT: Mast/stem cell growth factor receptor Kit; PDGFR: Platelet-derived growth factor receptor; Src: Proto-oncogene tyrosine-protein kinase Src; EGFR: Epidermal growth factor receptor; HER2: Human epidermal growth factor receptor 2; VEGFR: Vascular endothelial growth factor receptor; MEK: Mitogen-activated protein kinase; ERK: Extracellular signal-regulated kinase; FLT3: Fms-like tyrosine kinase 3; IGF-1R: Insulin-like growth factor 1 receptor; IR: Insulin receptor; ALK: Anaplastic lymphoma kinase; c-MET: Hepatocyte growth factor receptor; FGFR: Fibroblast growth factor receptor; CML: Ph+ chronic myeloid leukaemia; ALL: lymphoblastic leukaemia; MDS/MPD: Myelo displasic syndrome-myeloproliferative disorder; ASM: Aggressive systemic mastocytosis; HES: Hyper eosinophilic syndrome; CES: Chronic eosinophilic leukaemia; DFSP: Dermato-fibro sarcoma protuberan.