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Copyright ©The Author(s) 2021.
World J Gastroenterol. May 28, 2021; 27(20): 2507-2520
Published online May 28, 2021. doi: 10.3748/wjg.v27.i20.2507
Table 1 Tyrosine kinase inhibitors and antibody drug conjugates specific to c-MET and RON
Therapeutic agents
Manufacturer
Target
In vitro effects
Effects in animal tumor models
Clinical trial information
Status
Ref.
TKIs
ForetinibGlaxoSmithKlineMET, RON, VEGFR2, and PDGFRβInhibits MET and RON signaling and cell growth in various cancer cell linesAttenuates MET- and RON-mediated tumor growth in mouse tumor xenograft modelsSingle agent and combination with erlotinib or lapatinib for various types of advanced cancers in Phase II/III clinical trialsPhase I/II/IIIEder et al[82]
MGCD265MethylGeneMET, RON, VEGFR1, VEGFR2, VEGFR3, and TIE2Inhibits MET and RON signaling and cell growth in cancer cell linesAttenuates MET- and RON-mediated tumor growth in mouse tumor xenograft modelsSingle agent and combination with erlotinib or docetaxel for NSCLC in Phase II trialsPhase I/IIBelalcazar et al[83]
BMS-777607Bristol-Myers SquibbRON and METInhibits MET and RON signaling, cell growth, and invasion in cancer cell linesInhibits MET- and RON-mediated tumor growth in mouse tumor xenograft modelsMultiple ascending doses for metastatic cancers in Phase I trialsPhase ISharma et al[84]
MK-2461MerckMET, RON, FLT1, FLT3, FGFR1, FGFR2, and FGFR3Inhibits MET and RON signaling, cell growth, and migration in cancer cell linesInhibits MET- and RON-mediated tumor growth in mouse tumor xenograft modelsAntitumor efficacy is under evaluation in Phase II trialsPhase I/IIPan et al[85]
MK-8033MerckMET and RONInhibits MET and RON signaling, cell growth, and migration in cancer cell linesCauses tumor regression in mouse tumor xenograft modelsSafety, tolerability, dose, clinical activity and pharmaco-dynamics are under evaluation in Phase I trialsPhase INorthrup et al[86]
PHA665752PfizerMET and RONNANANAPreclinicalComoglio et al[87]
INC280NovartisMETNANANAPhase I/IIQin et al[88]
TivantinibArQuleMETNANANAPhase II/IIIRimassa et al[89]
Antibody drug conjugates
Zt/g4-doxorubicin-immuoliposomeTTUHSCRONModerately activates RON signaling and strongly induces RON endocytosisNo effect as naked antibody but completely inhibits tumors used as ADCsNAPreclinicalGuin et al[90]
Zt/g4-maytansinoid conjugateTTUHSCRONModerately activates RON signaling and strongly induces RON endocytosisNo effect as naked antibody but completely inhibits tumors used as ADCsNAPreclinicalFeng et al[91]
Zt/g4-MMAETTUHSCRONModerately activates RON signaling and strongly induces RON endocytosisNo effect as naked antibody but completely inhibits tumors used as ADCsNAPreclinicalYao et al[92]
H5B14-MMAETTUHSCRONNANANAPreclinicalYao et al[59]
SHR-A1403HengRuiMETHighly potent: 0.02 to 1.5 nmol/L for cell proliferationXenografts and PDXs, MET over-expressed and amplifiedNAPhase IYang et al[93]