alk-in-1

ALK-IN-1 (AP26113) is a potent ALK inhibitor with IC50 of 0.62 nM in a cell-free assay, demonstrated ability overcome Crizotinib resistance mediated by a L1196M mutation. Phase 2.

ALK/ROS1-IN-1 is a potent and selective anti-crizotinib-resistant ALK/ROS1 dual inhibitor (IC50s: 0.530 μM and 0.174 μM for ROS1 and ALK enzyme).

ALK EGFR-IN-1 (Compound 8l) is a dual inhibitor targeting both ALK and EGFR, effectively blocking their phosphorylation. It demonstrates potent inhibition of ALK EGFR mutants with IC50 values of 4.3 nM for EGFR L858R T790M in H1975 cells and 3.6 nM for EML4-ALK in BaF3 cells. This compound may be applicable in the research of non-small cell lung cancer (NSCLC) [1].

TRK/ALK-IN-1 is a potent dual inhibitor of TRK and ALK, exhibiting good correlation between its enzymatic inhibition and anti-proliferative activities, with IC50 values of 2.2 nM for TRKA, 9.3 nM for ALK WT, and 38 nM for ALK L1196M. It holds potential for cancer research applications.

EML4-ALK kinase inhibitor 1 (EML4 ALK kinase inhibitor 1) is a potent oral active inhibitor of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), with an IC50 of 1 nM.

ALK inhibitor 1 is a selective ALK kinase inhibitor.

SAR348830 is an ALK inhibitor, targeting anaplastic lymphoma kinase.

Ensartinib (X-396) is a potent dual ALK MET inhibitor with IC50 values of <0.4 nM for ALK and 0.74 nM for MET.

APG-2449, an orally active inhibitor of ALK, ROS1, and FAK, demonstrates antitumor efficacy in mouse models of non-small cell lung cancer (NSCLC) [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].

ALK-IN-12 is a highly potent and orally active inhibitor of anaplastic lymphoma kinase (ALK), demonstrating an exceptional IC50 value of 0.18 nM. Additionally, ALK-IN-12 displays inhibitory activity against insulin-like growth factor 1 receptor (IGF1R) and insulin receptor (InsR), with IC50 values of 20.3 nM and 90.6 nM, respectively. Notably, its antitumor effects have been observed, making it a promising compound for targeted cancer therapy.

ALK-IN-9 (compound 40) is a highly effective ALK inhibitor, demonstrating remarkable inhibitory activity against cell proliferation, with IC50 values of <0.2 nM for Ba F3-EML4-ALK, KM 12 (TPM3-TRKA), and KG-1 cell (OP2-FGFR1).

ALK EGFR-IN-2 is a potent dual inhibitor targeting ALK and EGFR, promoting apoptosis and G0 G1 cell cycle arrest in cancer cells. It effectively suppresses proliferation in H1975, PC9, and Baf3-EML4-ALK cancer cell lines, with IC50s of 0.0034, 0.0065, and 0.0018 μM, respectively [1].

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].

Trk-IN-10 (Compound 14j) is a highly effective inhibitor of TRK, with an IC50 of 0.86 nM against TrkA and 6.92 nM against TrkA G595R. As an RTK, Trk is a crucial drug target in solid tumors. Trk-IN-10 (IC50 = 350 nM against ALK) demonstrates superior selectivity in inhibiting Trk, potentially reducing toxicity [1].

ALK-IN-27 (compound 1) is a potent ALK inhibitor with an IC50 of 2.7 nM in Ba F3 CLIP1-LTK cells, demonstrating significant antitumor activity [1].

ALK EGFR-IN-3 is a dual ALK and EGFR inhibitor demonstrating potent anti-proliferative effects on various cancer cell lines, including H1975, PC9, and Baf3-EML4-ALK, with IC50 values of 0.1360, 0.0332, and 0.0339 μM [1].

PRO-6E is an orally active, Cereblon ligand-based PROTAC that promotes MET degradation, achieving up to 81.9% effectiveness at a concentration of 1 μM in MKN-45 cells. It demonstrates tumor growth inhibition both in vivo and in vitro, alongside inducing cell apoptosis and cell cycle arrest. Notably, its structure comprises a Cereblon ligand (blue), a linker (black), and an ALK/c-Met inhibitor Crizotinib component (pink). [1]

AP-1, a miniaturized proteolysis-targeting chimera (PROTAC) incorporating an anaplastic lymphoma kinase (ALK) ligand connected to (±)-thalidomide via an ultrashort linker, effectively degrades ALK fusion proteins such as NPM-ALK in Karpas-299 cells and EML4-ALK and ALKF1174L in SN-N-SH and NCI H3122 cells, respectively. Concentrations ranging from 10 to 300 nM are sufficient for its action, which is hindered by the proteasome inhibitor MG-132. Demonstrating selectivity, AP-1 exhibits cytotoxicity towards ALK-dependent Karpas-299 cells with an IC50 value of 0.1265 nM, while showing significantly less toxicity to non-ALK-dependent THP-1 cells (IC50 = 2,704 nM). Furthermore, it effectively reduces tumor volume in NCI H3122 mouse xenograft models at doses of 25, 50, and 100 mg/kg.

PF-06463922 acetate is a potent, selective brain-penetrable inhibitor of both anaplastic lymphoma kinase (ALK) and c-ros Oncogene 1 (ROS1) with strong activity against all known ALK and ROS1 mutants identified in patients with crizotinib-resistant disease. PF-06463922 is in clinical trials for the treatment of non–small cell lung cancer (NSCLC).

ALK5-IN-26 (EX-22) is an ALK (Activin receptor-like kinase) inhibitor with an IC50 ≤ 1 nM for ALK5.