alk g1202r

Repotrectinib (TPX-0005) is a potent ALK ROS1 TRK inhibitor, with IC50 values of 1.01 nM for WT ALK, 5.3 nM for SRC, 1.08 nM for ALK L1196M, and 1.26 nM for ALK G1202R.

F-1 is IC50s of 2.1 nM, 2.3 nM, 1.3 nM and 3.9 nM for ALKWT, ROS1WT, ALKL1196M and ALKG1202R, respectively. F-1 is a potent ALK and ROS1 dual inhibitor, suppresses phospho-ALK and its relative downstream signaling pathways.

ZX-29 is a potent and selective inhibitor of ALK with IC50 values of 2.1 nM, 1.3 nM, and 3.9 nM for ALK, ALK [L1196M], and ALK [G1202R] mutations, respectively. It also induces protective autophagy and exhibits antitumor effects.

JH-VIII-157-02 is an inhibitor of ALK and inhibits echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) with IC50s of 2 nM for EML4-ALK G1202R, EML4-ALKwt, EML4-ALK C1156Y, EML4-ALK F1174L, and EML4-ALK F1174L.

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.

X-376 (Ensartinib) is an orally available small molecule inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK) with potential antineoplastic activity. Upon oral administration, X-396 binds to and inhibits ALK kinase, ALK fusion proteins, and ALK point mutation variants. Inhibition of ALK leads to the disruption of ALK-mediated signaling and eventually inhibits tumor cell growth in ALK-expressing tumor cells. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development.

Trk-IN-7 (compound I-6) is a highly potent TRK inhibitor, with IC50 values of 0.25-10 nM for TRKA, TRKB, and TRKC, respectively. It also shows significant inhibition of EML4-ALK (IC50 <15 nM) and ALK mutations G1202R, C1156Y, R1275Q, F1174L, L1197M, and G1269A (IC50 = 5-50 nM) [1].

SIAIS117, a potent Brigatinib-PROTAC degrader, effectively degrades the ALK G1202R point mutation through its design based on Brigatinib and VHL-1 conjunction. It inhibits the proliferation of SR and H2228 cancer cell lines, demonstrating potential anti-proliferative effects against small cell lung cancer [1].

ALK-IN-21 (Compound B10), a proficient ALK inhibitor targeting the ALKG1202R mutation, demonstrates significant inhibitory activity with IC50 values of 4.59 nM against ALK WT, 2.07 nM against ALK L1196M, and 5.95 nM against ALK G1202R. Moreover, ALK-IN-21 effectively suppresses proliferation in ALK-positive Karpas299 and H2228 cells, achieving IC50 values of 0.07 μM. It is applicable for anaplastic large cell lymphoma research [1].

SIAIS164018, a PROTAC-based ALK and EGFR degrader derived from Brigatinib, exhibits IC50 values of 2.5 nM for ALK and 6.6 nM for ALK G1202R. It significantly hampers cancer cell migration and invasion, induces G1 cell cycle arrest, and triggers apoptosis, demonstrating superior properties compared to Brigatinib [1].

CPD-1224, an orally active derivative that binds cereblon ligands to ALK inhibitors, specifically targets and degrades EML4-ALK oncogenic fusions, including ALK and its mutants L1196M G1202R.

SIAIS164018 hydrochloride is a PROTAC-based degrader targeting ALK and EGFR, exhibiting IC50 values of 2.5 nM for ALK and 6.6 nM for ALK G1202R. It effectively suppresses cancer cell migration and invasion, induces G1 cell cycle arrest, and promotes apoptosis, demonstrating superior properties compared to Brigatinib [1].