3.
Specific inhibitors of growth factor cascades and signaling elements involved in sustained growth, survival and/or drug resistance of cancer progenitor cells and angiogenic process
| Targeted signaling element | Name of inhibitor |
|---|---|
| EGFR family member inhibitor | |
| Anti-EGFR (erbB1) antibody | mAb-C225, IMC-C225 |
| Anti-EGF antibody | ABX-EGF |
| EGFR-TKI | Gefitinib, erlotinib, AG1478, EKB-569 |
| Anti-erbB2 antibody | Trastuzumab |
| EGFR-erbB2-TKI | PKI-166, TAK165, GW572017 (lapatinib) |
| erbB1/erbB2/erbB3/erbB4-TKI | CI1033 |
| Other growth factor signaling inhibitor | |
| Hedgehog | SMO inhibitor cyclopamine, anti-SHH antibody |
| Anti-Wnt antibody, WIF-1 | |
| Wnt/ -catenin | |
| Notch | -secretase inhibitor DAPT, GSI-18 |
| PDGFRβ/KIT/ABL-TKI | Imatinib mesylate (STI571) |
| Sorafenib | |
| PDGFR /FLT3 | |
| VEGF | Anti-VEGF antibody (bevacizumab), As-VEGF |
| VEGFR | Anti-VEGFR antibody |
| VEGFR1,2 and 3 | CEP-7055, AZD2171 |
| AMG 706, Vatalanib (PTK787/ZK 222584) | |
| VEGFR1,2,3 /PDGFRβ/KIT | |
| Signaling element inhibitor | |
| Telomerase | Telomerase template antagonist |
| MYC | As-MYC |
| Bcl-2 | ABT-737 |
| PI3K | LY294002, rapamycin, CCI-779 |
| NF-κ B inhibitor | IkBβ inhibitor, sulfasalazine, bortezomib (PS-341) |
| Src-family and ABL-TKI | PD180970 |
| Src-family-TKI | CGP-76030 |
| Fusion oncoprotein inhibitor | |
| BCR-ABL | Imatinib mesylate (STI571), dasatinib (BMS-354825), nilotinib |
| Imatinib mesylate (STI571) | |
| FIP1L1-PDGFRα | |
| All-trans retinoic acid | |
| PML-RAR-α | |
| Drug transporter inhibitor | |
| ABC multidrug efflux transporter | |
| MDR1/ABCB1/P-gp | MS-209, gefitinib, CI1033, tamoxifen, cyclopamine |
| MRP1/ABCC1 | MS-209 |
| ABCG2/BCRP | Gefitinib, CI1033, tamoxifen derivatives, cyclopamine |
| Organic cation intracellular transporter Oct-1 | Prazosin |
DAPT, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester;EGFR, epidermal growth factor receptor; KIT, stem cell factor (SCF) receptor;GSI-18, [11-endo]-N-(5,6,7,8,9,10-hexahydro-6,9-methanobenzo[a][8]annulen-11-ylthiophene-2-sulfonamide;MDR1, multidrug resistance 1;MRP1, multidrug resistance-associated protein 1;MRP2, multidrug resistance-associated protein 2;NF-kB, nuclear factor-kB;PDGFR, platelet-derived growth factor receptor;P-gp, P-glycoprotein;PI3K, phosphatidylinositide-3'-kinase;TKI, tyrosine kinase inhibitor;VEGF, vascular epithelial growth factor;VEGFR, vascular epithelial growth factor receptor;WIF-1, Wingless inhibitory factor-1;Wnt, Wingless ligand