| 包装 | 价格(元) |
| 5mg | 电议 |
| 25mg | 电议 |
| 100mg | 电议 |
Preparation Method | To confirm compound 13 as a pan-RAF inhibitor, it was evaluated in a whole cell-based KiNativ assay developed. LY3009120 was incubated with A375 whole cell lysate for 15 min, and the binding affinities of over 170 kinases were determined by direct competitive binding with an ATP analog. |
Applications | LY3009120 bound ARAF, BRAF, and CRAF native proteins with IC50 values of 44, 31-47, and 42 nM, respectively. |
Cell lines | CRC cell lines |
Preparation Method | CRC cell lines treated with either DMSO or LY3009120 (0.5 μM) for the times indicated, fixed and stained with propidium iodide and analyzed for cell cycle by flow cytometry. |
Reaction Conditions | LY3009120 (0.5 μM) for 24h/48h |
Applications | Treatment of both BRAFmut and KRASmut CRC cell lines with LY3009120 induced an increase in the percentage of cells in G1, indicative of G1 cell cycle arrest, with significant debris accumulation (sub-G1 population) in the HCT 116 and Colo 205 cell lines. |
Animal models | Female NIH nude rats |
Preparation Method | 5 million tumor cells in inoculation media were implanted subcutaneously in the right hind flank of female NIH nude rats. When tumors reached ~400 mm3, animals were randomized into groups of 8 10 and treated as indicated in the respective figure legends. LY3009120 was administered orally and animals were monitored for toxicity. |
Dosage form | 20-30mg/kg LY3009120 twice daily ( orally) |
Applications | LY3009120 treatment reduced pMEK1/2 in all HT-29 xenografts and reduced pERK1/2 in the majority of HT-29 xenografts. |
| 产品描述 | LY3009120 is a pan-RAF and RAF dimer inhibitor that inhibits all RAF isoforms and occupies both protomers in RAF dimers. LY3009120 bound ARAF, BRAF, and CRAF native proteins with IC50 values of 44, 31-47, and 42 nM, respectively. LY3009120 induces BRAF-CRAF dimerization but inhibits the phosphorylation of downstream MEK and ERK, suggesting that it effectively inhibits the kinase activity of BRAF-CRAF heterodimers[1,7]. Treatment of both BRAFmut and KRASmut CRC cell lines with LY3009120 induced an increase in the percentage of cells in G1, indicative of G1 cell cycle arrest, with significant debris accumulation (sub-G1 population) in the HCT 116 and Colo 205 cell lines[2]. LY3009120 has an anti adipogenic effect on 3T3 L1 cells[3]. LY3009120 suppressed BRAF-related downstream pathway molecules and induced cleavage of poly ADP-ribose polymerase in all examined NSCLC cell lines. LY3009120 also inhibited in vivo tumor growth in NSCLC cells harboring the BRAF non-V600E mutation[4]. LY3009120 treatment reduced pMEK1/2 in all HT-29 xenografts and reduced pERK1/2 in the majority of HT-29 xenografts while LY3009120 had unremarkable effects on the phosphorylation of MEK1/2 and ERK1/2 in the Colo 320HSR xenograft model at a 50% increased dose[2]. In vivo, LY3009120 significantly alleviated dextran sulfate sodium (DSS)-induced colitis as indicated by prevention of body weight loss, colon shortening, and decreased mortality[5]. Combinatory treatment with LY3009120 and abemaciclib synergistically inhibited proliferation of tumor cells in vitro and led to tumor growth regression in xenograft models with a KRAS, NRAS or BRAF mutation at the doses of two drugs that were well tolerated in combination[6]. References: |
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