alk wild

ALK-IN-6 is an orally bioavailable inhibitor of anaplastic lymphoma kinase (ALK, IC50s: 71 nM, 18.72 nM, and 36.81 nM for ALK wild, ALK F1196M and ALK F1174L).

Crizotinib (PF-02341066) is an ATP-competitive small-molecule tyrosine kinase inhibitor of c-MET (IC50: 8 nM) and ALK (IC50: 20 nM) receptors.

JWJ-01-378 is a selective TRK PROTAC degrader. It effectively degrades wild-type TRK and TPM3-TRKA fusion proteins while inhibiting downstream pERK signaling, but shows limited degradation effects on TRK inhibitor-resistant mutants and ALK fusion proteins. Additionally, JWJ-01-378 effectively suppresses cancer cell proliferation.

EGFR-IN-176 is an orally active and ATP-competitive inhibitor specifically targeting mutated forms of EGFR, particularly the C797S-mediated EGFR triple mutant. It effectively inhibits the activation of the AKT signaling pathway and induces apoptosis in Ba/F3 and PC-9 cells, which express EGFR19del/T790M/C797S or EGFRL858R/T790M/C797S mutations, respectively. EGFR-IN-176 selectively blocks EGFR signaling in cell lines with the EGFR triple mutation, without affecting wild-type EGFR expressed in A431 cells. Additionally, EGFR-IN-176 effectively inhibits ALK enzyme activity with an IC50 of less than 0.5 nM and is useful in the study of non-small cell lung cancer.

Ensartinib hydrochloride (X-396 dihydrochloride) is a potent new-generation ALK inhibitor with high activity against CNS metastases and a broad range of known crizotinib-resistant ALK mutations. It potently inhibits both wild-type ALK and ALK variants (C1156Y, F1174, G1202R, L1196M, S1206R, and T1151 mutants) with in vitro IC50s of <4 nM.

Belizatinib (TSR-011) is an effective, oral and dual inhibitor of ALK (IC50: 0.7 nM, wild-type recombinant ALK) and TRKA, TRKB, and TRKC.

CJ-2360 is a potent, orally active ALK inhibitor, capable of acting on wild-type ALK (IC50: 2.2 nM) and F1197M (IC50: 4.0 nM), G1269A (IC50: 8.8 nM), L1196M (IC50: 6.3 nM) and S1206Y ALK mutant (IC50: 8.9 nM). CJ-2360 strongly inhibited two clinically reported ALK mutants (C1156Y and L1196M) and 468 kinases (LTK, MERTK, CLK1, DAPK1, and DAPK2).