| Identification | Back Directory | [Name]
KO-947 | [CAS]
1695533-89-1 | [Synonyms]
KO-947
KO947;KO-947;KO 947
6-benzyl-3-(pyridin-4-yl)-5,6-dihydro-1H-pyrazolo[4,3-g]quinazolin-7(8H)-one
7H-Pyrazolo[4,3-g]quinazolin-7-one, 1,5,6,8-tetrahydro-6-(phenylmethyl)-3-(4-pyridinyl)- | [Molecular Formula]
C21H17N5O | [MDL Number]
MFCD31657422 | [MOL File]
1695533-89-1.mol | [Molecular Weight]
355.39 |
| Chemical Properties | Back Directory | [Boiling point ]
704.1±60.0 °C(Predicted) | [density ]
1.354±0.06 g/cm3(Predicted) | [storage temp. ]
4°C, protect from light | [solubility ]
DMSO:66.75(Max Conc. mg/mL);187.82(Max Conc. mM) | [form ]
A crystalline solid | [pka]
13.32±0.20(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Description]
KO947 is an ERK inhibitor (IC50 = <50 nM for ERK2). It is greater than 50-fold selective for ERK over a panel of 450 kinases. KO947 reduces phosphorylation of the ERK target p90 ribosomal S6 kinase (RSK) in A375 cancer cells containing constitutively active B-RAFV600E with an IC50 value of less than 250 nM. It inhibits proliferation of A375 cells, as well as mutant K-Ras-expressing HCT116 and H358 cancer cell lines (IC50s = 50-250 nM for all). | [Uses]
KO-947 is a potent and selective inhibitor of ERK1/2 kinases with potential utility in MAPK pathway dysregulated tumors. | [in vivo]
In cell-line derived xenograft studies, KO-947 profoundly suppresses ERK signaling for up to five days after a single dose and induces regressions in RAS- and RAF-mutant melanoma, NSCLC and pancreatic cancer models on administration schedules ranging from daily to weekly. Intermittent dosing enables comparable antitumor activity at reduced dose-intensity[1]. | [IC 50]
ERK1; ERK2 | [References]
[1] Burrows F, et al. KO-947, a potent ERK inhibitor with robust preclinical single agent activity in MAPK pathway dysregulated tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5168. doi:10.1158/1538-7445.AM2017-5168. |
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