| Identification | Back Directory | [Name]
LY-3009120 | [CAS]
1454682-72-4 | [Synonyms]
DP 4978
CS-1616
LY-3009120
LY-3009120（DP-4978）
LY3009120; LY-3009120; LY 3009120; DP-4978; DP 4978; DP4978
N-(3,3-dimethylbutyl)-N'-[2-fluoro-4-methyl-5-[7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl]phenyl]-
N-(3,3-Dimethylbutyl)-N'-[2-fluoro-4-methyl-5-[7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl]phenyl]urea
Urea, N-(3,3-dimethylbutyl)-N'-[2-fluoro-4-methyl-5-[7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl]phenyl]- | [Molecular Formula]
C23H29FN6O | [MDL Number]
MFCD28411374 | [MOL File]
1454682-72-4.mol | [Molecular Weight]
424.51 |
| Chemical Properties | Back Directory | [density ]
1?+-.0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
insoluble in H2O; insoluble in EtOH; ≥4.25 mg/mL in DMSO with gentle warming and ultrasonic | [form ]
solid | [pka]
13.52±0.70(Predicted) | [color ]
Light yellow to khaki |
| Hazard Information | Back Directory | [Uses]
LY 3009120 is a potent pan-Rad inhibitor used in the inhibition of tumors. Dose-dependant inhibition. | [Definition]
ChEBI: LY3009120 is a member of the class of pyridopyrimidines that is pyrido[2,3-d]pyrimidine substituted by methylamino, 5-{[(3,3-dimethylbutyl)carbamoyl]amino}-4-fluoro-2-methylphenyl, and methyl groups at positions 2, 6 and 7, respectively. It is a potent pan RAF inhibitor which inhibits BRAF(V600E), BRAF(WT) and CRAF(WT) (IC50 = 5.8, 9.1 and 15 nM, respectively). It also inhibits RAF homo- and heterodimers and exhibits anti-cancer properties. It has a role as a necroptosis inhibitor, an apoptosis inducer, an antineoplastic agent, a B-Raf inhibitor and an autophagy inducer. It is a pyridopyrimidine, a biaryl, an aromatic amine, a member of phenylureas, a member of monofluorobenzenes, an aminotoluene and a secondary amino compound. | [Biological Activity]
ly3009120 is a pan-raf and raf dimer inhibitor. it inhibits braf wt, craf, wt, brafv600e, and brafv600e+g468a with the ic50 values of 9.1, 15, 5.8, and 17 nm, respectively. [1]raf is family of serine/threonine-protein kinase mediates ras gtpases and the mapk/erk cascade. it involves in proliferation, differentiation, apoptosis, survival and oncogenic transformation. [1]in nras mutant sk-mel2 cells or kras mutant hct116 cells, ly3009120 inhibits the kinase activity of craf in a dose-dependent manner and induces braf/craf heterodimerization. it also blocks phospho-mek and -erk and induces minimal paradoxical activation in ras mutant cells. moreover, treatment of braf v600e a375 melanoma cells by ly3009120 for 24 hr predominantly induces a g0/g1 arrest with more than 95% cells in g0/g1 phase. [1]in nude rats bearing a375 xenograft tumors, oral ly3001920 treatment exerts a dose-dependent inhibition of phospho-mek and –erk. 15 or 30 mg/kg ly3009120 shows near complete tumor regression in nude rats bearing pdx tumors. [1] | [in vivo]
LY3009120 (20 mg/kg bid) displays significant activity in in vivo BRAFmut and KRASmut CRC xenograft models. In Colo 205 xenografts (BRAFmut), LY3009120 results in statistically significant tumor regression, while treatment of HCT 116 xenografts (KRASmut) results in statistically significant inhibition of tumor growth. LY3009120 treatment reduces pMEK1/2 in all HT-29 xenografts and reduces pERK1/2 in the majority of HT-29 xenografts[1]. LY3009120 (15 or 30 mg/kg) achieves almost complete tumor growth regression, and inhibits downstream phospho-MEK and ERK by approximately 70% and 60%, respectively, in the H2405 model[2]. | [IC 50]
BRafV600E: 5.8 nM (IC50); Braf: 9.1 nM (IC50); CRAF: 15 nM (IC50) | [storage]
Store at -20°C | [References]
1. peng sb, henry jr, kaufman md et al. inhibition of raf isoforms and active dimers by ly3009120 leads to anti-tumor activities in ras or braf mutant cancers. cancer cell. 2015 sep 14;28(3):384-98. |
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