| Identification | Back Directory | [Name]
KRC-108 | [CAS]
1146944-35-5 | [Synonyms]
KRC-108
2-Pyridinamine, 3-(2-benzoxazolyl)-5-[1-(4-piperidinyl)-1H-pyrazol-4-yl]- | [Molecular Formula]
C20H20N6O | [MDL Number]
MFCD28138416 | [MOL File]
1146944-35-5.mol | [Molecular Weight]
360.41 |
| Hazard Information | Back Directory | [Description]
KRC-108 is a multiple kinase inhibitor. KRC-108 is a potent inhibitor of Ron, Flt3 and TrkA as well as c-Met. KRC-108 inhibited oncogenic c-Met M1250T and Y1230D more strongly than wild type c-Met. The anti-proliferative activity of KRC-108 was measured by performing a cytotoxicity assay on a panel of cancer cell lines. The GI(50) values (i.e., 50% inhibition of cell growth) for KRC-108 ranged from 0.01 to 4.22 μM for these cancer cell lines. KRC-108 was also effective for the inhibition of tumor growth in human HT29 colorectal cancer and NCI-H441 lung cancer xenograft models in athymic BALB/c nu/nu mice. This molecule should serve as a useful lead for inhibitors targeting kinases and may lead to new therapeutics for the treatment of cancer. (source: Invest New Drugs. 2012 Apr;30(2):518-23. doi: 10.1007/s10637-010-9584-2. Epub 2010 Nov 16. ). | [Uses]
KRC-108, an aminopyridine, is an orally active multiple kinase inhibitor with IC50s of 80 nM, 23 nM, 3 nM, 70 nM, 30 nM, 39 nM for c-Met, c-Met M1250T, c-Met Y1230D, Ron, Flt3 and TrkA, respectively. KRC-108 induces cell cycle arrest, apoptotic cell death, and autophagy. KRC-108 exhibits anti-tumor activity in vivo in HT29 colorectal cancer, NCI-H441 lung cancer xenograft models in athymic BALB/c nu/nu mice[1]. | [IC 50]
c-Met: 80 nM (IC50); c-Met M1250T: 23 nM (IC50); c-Met Y1230D: 3 nM (IC50); Ron: 70 nM (IC50); Flt3: 30 nM (IC50); TrkA: 39 nM (IC50); ALK: 780 nM (IC50); VEGFR2: 1660 nM (IC50) | [References]
[1] Sun-Young Han, et al. Evaluation of a multi-kinase inhibitor KRC-108 as an anti-tumor agent in vitro and in vivo. Invest New Drugs. 2012 Apr;30(2):518-23. DOI:10.1007/s10637-010-9584-2
[2] Hyo Jeong Lee, et al. Characterization of KRC-108 as a TrkA Kinase Inhibitor with Anti-Tumor Effects. Biomol Ther (Seoul). 2022 Jul 1;30(4):360-367. DOI:10.4062/biomolther.2021.195 |
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