Ceritinib (LDK378)

Non-specific ALK Inhibitor

GSK1838705A : IGF-1R, IC50=2.0 nM; IR, IC50=1.6 nM, ALK, IC50=0.5 nM.

FDA-approved ALK Inhibitor

Crizotinib (PF-02341066) : Approved by FDA for non-small cell lung carcinoma (NSCLC).

Newest ALK Inhibitor

ASP3026 ^New : Novel and selective inhibitor for ALK with IC50 of 3.5 nM.

Classic ALK Inhibitor

TAE684 (NVP-TAE684) : Potent and selective ALK inhibitor with IC50 of 3 nM, 100-fold more sensitive for ALK than InsR.

Lorlatinib (PF-6463922) ^New

PF-06463922 is a potent, dual ALK/ROS1 inhibitor with K_i of <0.02 nM, <0.07 nM, and 0.7 nM for ROS1, ALK (WT), and ALK (L1196M), respectively. PF-06463922 induces apoptosis. Phase 1.

Erlotinib ^New

Erlotinib is an EGFR inhibitor with IC50 of 2 nM, >1000-fold more sensitive for EGFR than human c-Src or v-Abl. Erlotinib induces autophagy.

Bemcentinib (R428) ^New

R428 (BGB324) is an inhibitor of Axl with IC50 of 14 nM, >100-fold selective for Axl versus Abl. Selectivty for Axl is also greater than Mer and Tyro3 (50-to-100- fold more selective) and InsR, EGFR, HER2, and PDGFRβ (100- fold more selective).

TAE684 (NVP-TAE684)

TAE684 (NVP-TAE684) is a potent and selective ALK inhibitor with IC50 of 3 nM in a cell-free assay, 100-fold more sensitive for ALK than InsR. TAE684 (NVP-TAE684) induces cell cycle arrest and apoptosis.

GSK1838705A

GSK1838705A is a potent IGF-1R inhibitor with IC50 of 2.0 nM, modestly potent to IR and ALK with IC50 of 1.6 nM and 0.5 nM, respectively, and little activity to other protein kinases.

Features:A small-molecule kinase inhibitor of IGF-1R and the insulin receptor.

Alectinib (CH5424802)

Alectinib (CH5424802, AF-802, RG-7853) is a potent ALK inhibitor with IC50 of 1.9 nM in cell-free assays, sensitive to L1196M mutation and higher selectivity for ALK than PF-02341066, NVP-TAE684 and PHA-E429.

AP26113-analog (ALK-IN-1)

AP26113-analog (ALK-IN-1) is an analog of AP26113 which is a potent and selective ALK inhibitor. It is also an inhibitor of EGFR.

Features:At least 10-fold more potent and selective in ALK inhibition relative to crizotinib.

ASP3026

ASP3026 is a novel and selective inhibitor for ALK with IC50 of 3.5 nM. Phase 1.

AZD3463

AZD3463 is a novel orally bioavailable ALK inhibitor with K_i of 0.75 nM, which also inhibits IGF1R with equivalent potency. AZD3463 suppresses cell viability by inducing both cell apoptosis and autophagy.

Gefitinib (ZD1839)

Gefitinib (ZD-1839) is an EGFR inhibitor for Tyr1173, Tyr992, Tyr1173 and Tyr992 in the NR6wtEGFR and NR6W cells with IC50 of 37 nM, 37nM, 26 nM and 57 nM, respectively. Gefitinib promotes autophagy and apoptosis of lung cancer cells via blockade of the PI3K/AKT/mTOR pathway.

Features:A potent EGFR tyrosine kinase inhibitor.