CSF1R-IN-2

CSF1R-IN-2 (compound 5) is an oral-active inhibitor of SRC, MET and c-FMS, with IC50 values of 0.12 nM, 0.14 nM and 0.76 nM for SRC, MET and c-FMS respectively[1].

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Src

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> c-Fms

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> c-Met/HGFR

IC50: 0.12 nM (SRC), 0.14 nM (MET), 0.76 nM (c-FMS)[1].

CSF1R-IN-2 (compound 5) causes the suppression of MET autophosphorylation as well as the downstream STAT3, ERK and AKT phosphorylation at IC50 values of around 1-3 nM in SNU-5 and MKN-45 cell lines[1].

CSF1R-IN-2 (compound 5: p.o., BID, 13 days) treatment results in an 85% tumor regression and no body weight loss is observed after 21 days treatment in mice[1]. CSF1R-IN-2 (compound 5: p.o., BID, 10 days) demonstrates the ability to inhibit tumor growth at 44% and 67% at the dose of 5 mg/kg, BID and 15 mg/kg, BID, respectively in SCID/Beige mice[1]. CSF1R-IN-2 (compound 5) inhibits MET activity in MKN-45 tumors following oral administration in mice[1]. Animal Model: Mice bearing LU2503 tumors patient derived xenograft (PDX) NSCLC model[1]. Dosage: 15 mg/kg. Administration: PO, BID (twice daily) for 13 days. Result: Resulted in an 85% tumor regression and no body weight loss was observed after 21 days treatment. Animal Model: SCID/Beige mice bearing Ba/F3 ETV6-CSF1R tumors with average tumor size of ~180 mm3[1]. Dosage: 5 and 15 mg/kg. Administration: PO, BID (twice daily) for 10 days. Result: Demonstrated the ability to inhibit tumor growth at 44% and 67% at the dose of 5 mg/kg, BID and 15 mg/kg, BID, respectively.

[1]. WO 2019023417 A1.