| Target |
Clinical agents |
Activity |
| BRAF |
Vemurafenib, Dabrafenib LGX818 RO5212054 |
Selectively binds to and inhibits activated BRAF, inhibiting the proliferation of tumor cells with mutated BRAF gene |
| MEK |
Trametinib, Selumetinib Pimasertib, TAK-733 MSC2015103B |
Binds to and inhibits MEK 1 and MEK 2, resulting in inhibition of growth factor-mediated cell signaling and tumor cell proliferation |
| Cobimetinib |
Binds to and inhibits the catalytic activity of MEK1, resulting in inhibition of activating ERK2 phosphorylation and tumor cell proliferation |
| RO4987655 |
Binds to and inhibits MEK 1, which may result in inhibition of MEK-dependent cell signaling and tumor cell proliferation |
| Dual MEK-RAF |
RO5126766 |
Specifically inhibits kinase activities of Raf and MEK, resulting in inhibition of target gene transcription that promotes malignant cell transformation |
| Pan-RAF |
Sorafenib |
Blocks RAF kinase (regardless of mutation status) and other kinases that control cell division and proliferation |
| RAF265 |
Binds and inhibits Raf kinases and VEGFR-2, which may result in reduction of tumor cell growth and proliferation |
| PI3K |
BKM120, XL147 ZSTK474 PX-866, GDC-0941 |
Reversibly binds to class 1 PI3Ks in an ATP-competitive manner, inhibiting the production of PIP3 and activation of the PI3K signaling pathway; this may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations |
| AKT |
MK2206, GSK2110183 GDC-0068 |
Binds to and inhibits AKT in a non-ATP-competitive manner, resulting in inhibition of the PI3K/AKT signaling pathway and tumor cell proliferation and induction of tumor cell apoptosis |
| mTOR |
AZD8055 Temsirolimus Ridaforolimus |
Binds to and inhibits mTOR, resulting in decreased expression of mRNAs necessary for cell cycle progression and arresting cells in the G1 phase of the cell cycle |
| Sirolimus |
Binds to FKBP-12 to generate an immunosuppressive complex that binds to and inhibits mTOR, resulting in inhibition of T lymphocyte activation and proliferation that occurs in response to antigenic and cytokine (IL-2, IL-4, and IL-15) stimulation and inhibition of antibody production |
| Everolimus, OSI-027 |
Binds to and inhibits both the raptor-mTOR complex 1 (TORC1) and the rictor-mTOR complex 2 (TORC2), resulting in tumor cell apoptosis and inhibition of tumor cell proliferation |
| Dual PI3K/mTOR |
XL765/SAR245409 BEZ235, GDC-0980 |
Inhibits both PI3K kinase and mTOR kinase, which may result in tumor cell apoptosis and growth inhibition in susceptible tumor cell populations. |
| GSK2126458 |
Binds to and inhibits PI3K in the PI3K/mTOR signaling pathway, which may trigger the translocation of cytosolic Bax to the mitochondrial outer membrane, increasing mitochondrial membrane permeability and inducing apoptotic cell death |
| SF1126 |
Selectively binds to cell surface integrins and, upon cell entry, the agent is hydrolyzed to the active drug SF1101; Inhibits all isoforms PI3K, mTOR and DNA-PK, wich may inhibit tumor cell and tumor endothelial cell proliferation and survival |
| CDK4/6 |
LEE011 LY2835219 Palbociclib |
Specifically inhibits CDK4 and 6, thereby inhibiting Rb protein phosphorylation, that prevents CDK-mediated G1-S phase transition, thereby arresting the cell cycle in the G1 phase, suppressing DNA synthesis and inhibiting cancer cell growth |
| Src |
Dasatinib |
Binds to and inhibits the growth-promoting activities of SRC-family protein-tyrosine kinases |
| Met |
Tivantinib |
Binds to the c-Met protein and disrupts c-Met signal transduction pathways, which may induce cell death in tumor cells overexpressing c-Met protein or expressing consitutively activated c-Met protein |
| IGF1R |
Ganitumab |
Binds to membrane-bound IGF-1R, preventing binding of the ligand IGF-1 and the subsequent triggering of the PI3K/Akt signaling pathway; inhibition of this survival signaling pathway may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis |
| HSP90 |
XL888 |
Specifically binds to Hsp90, inhibiting its chaperone function and promoting the proteasomal degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival; inhibition of tumor cell proliferation may result |
| CTLA-4 |
Ipilimumab |
enhances T-cell activation and blocks B7-1 and B7-2 T-cell co-stimulatory pathways |
| PD-1 |
Nivolumab |
Binds to and blocks the activation of PD-1, an Ig superfamily transmembrane protein, by its ligands PD-L1 and PD-L2, resulting in the activation of T-cells and cell-mediated immune responses against tumor cells or pathogens |
| PD-L1 |
MDX-1105 Pembrolizumab MPDL3280A |
Binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells |
| Interleukin-2 |
Aldesleukin |
Binds to and activates IL-2 receptor; activation of tyrosine kinase Jak3; and phosphorylation of tyrosine residues on IL-2R beta chain, resulting in an activated receptor complex. may induce T cell-mediated tumor regression in some tumor types |
