Missing content? – Request curation!
Request curation for specific Genes, Variants, or PubMed publications.
Have questions, comments, or suggestions? - Let us know!
Email us at : ckbsupport@genomenon.com
Ref Type | Journal Article | ||||||||||||
PMID | (30210922) | ||||||||||||
Authors | Wang L, Gao M, Tong M, Xie C, He Y, Fu L, Li Y, Fu H, Lou L | ||||||||||||
Title | Pharmacologic characterization of CT-711, a novel dual inhibitor of ALK and c-Met. | ||||||||||||
|
|||||||||||||
URL | |||||||||||||
Abstract Text | Anaplastic lymphoma kinase (ALK) is a validated molecular target for patients harboring ALK rearrangement, which triggers the development of ALK inhibitors. However, the activation of mesenchymal-epithelial transition factor (c-Met) has emerged as a common cause of acquired resistance induced by selective ALK inhibitors. Herein, we report the first preclinical characterization of CT-711, a novel dual inhibitor of ALK and c-Met. CT-711 demonstrates potent inhibitory activity against ALK kinase activity. Moreover, CT-711 profoundly inhibits ALK signal transduction and thereby induces G1 phase arrest and apoptosis, and results in remarkable anti-proliferative activity against ALK-driven cancer cells. Furthermore, CT-711 effectively inhibits c-Met kinase activity and potently overcomes the resistance mediated by c-Met activation. When orally administered to nude mice bearing xenografts, CT-711 exhibits favorable pharmacokinetic properties and robust antitumor activity. It is noteworthy that CT-711 is superior to crizotinib, the first-in-class ALK inhibitor, in the treatment of ALK-driven cancers in various models. The results of the current study provide a solid foundation for the clinical investigation of CT-711 in patients with tumors harboring ALK rearrangement. |
Molecular Profile | Treatment Approach |
---|
Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
---|
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
TQ-B3139 | TQB3139|TQ B3139|CT-711|CT 711|CT711|Envonalkib | ALK Inhibitor 32 MET Inhibitor 59 | TQ-B3139 (CT-711) inhibits MET and ALK, with activity against ALK mutations, potentially resulting in decreased Alk signaling, induction of cell cycle arrest and apoptosis in tumor cells, and reduced proliferation and tumor growth (PMID: 30210922). |
Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
---|
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
EML4 - ALK ALK C1156Y | Advanced Solid Tumor | sensitive | TQ-B3139 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, TQ-B3139 (CT-711) inhibited proliferation of cells expressing EML4-ALK with ALK C1156Y in culture and inhibited tumor growth in a cell line xenograft model (PMID: 30210922). | 30210922 |
EML4 - ALK ALK L1152R | Advanced Solid Tumor | sensitive | TQ-B3139 | Preclinical - Cell culture | Actionable | In a preclinical study, TQ-B3139 (CT-117) inhibited proliferation of a cells expressing EML4-ALK with ALK L1152R in culture (PMID: 30210922). | 30210922 |
EML4 - ALK | Advanced Solid Tumor | sensitive | TQ-B3139 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, TQ-B3139 (CT-711) inhibited proliferation of cells expressing EML4-ALK in culture and inhibited tumor growth in a cell line xenograft model (PMID: 30210922). | 30210922 |
EML4 - ALK ALK L1196M | Advanced Solid Tumor | sensitive | TQ-B3139 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, TQ-B3139 (CT-711) inhibited proliferation of cells expressing EML4-ALK with ALK L1196M in culture and inhibited tumor growth in a cell line xenograft model (PMID: 30210922). | 30210922 |
EML4 - ALK | lung non-small cell carcinoma | sensitive | TQ-B3139 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, TQ-B3139 (CT-711) inhibited Alk signaling and proliferation and induced cell cycle arrest and apoptosis in non-small cell lung cancer cell lines harboring EML4-ALK in culture and induced tumor regression in cell line xenograft models (PMID: 30210922). | 30210922 |
ALK F1174L | neuroblastoma | sensitive | TQ-B3139 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, TQ-B3139 (CT-711) inhibited proliferation of a neuroblastoma cell line harboring ALK F1174L in culture and inhibited tumor growth in a cell line xenograft model (PMID: 30210922). | 30210922 |
EML4 - ALK ALK R1275Q | Advanced Solid Tumor | sensitive | TQ-B3139 | Preclinical - Cell culture | Actionable | In a preclinical study, TQ-B3139 (CT-711) inhibited proliferation of cells expressing EML4-ALK with ALK R1275Q in culture (PMID: 30210922). | 30210922 |