| 名稱 | LY3009120 |
| 描述 | LY3009120 (DP-4978) is a potent pan-Raf inhibitor with IC50 of 44 nM, 31-47 nM, and 42 nM for A-raf, B-Raf, and C-Raf in A375 cells, respectively. Phase 1. |
| 細(xì)胞實(shí)驗(yàn) | Brie?y, cells are grown in DMEM high glucose supplemented with 10% characterized fetal bovine serum and 1% penicillin/streptomycin/L -glutamine at 37℃, 5% CO2, and 95% humidity. Cells are allowed to expand until 70-95% con?uency. A serial dilution of test compound is dispensed into a 384-well black clear bottom plate. 625 cells are added per well in 50 μL of complete growth medium. Plates are incubated for 67 h at 37℃, 5% CO2 , and 95% humidity. Then, 10 μL of a 440 μM solution of resazurin in PBS is added to each well of the plate and plates are incubated for an additional 5 h at 37℃, 5% CO2, and 95% humidity. Plates are read on a Synergy2 reader using an excitation of 540 nm and an emission of 600 nm. Data are analyzed using Prism software to calculate IC 50 values.(Only for Reference) |
| 激酶實(shí)驗(yàn) | Kinase activity measurement using KiNativ assays: Compounds are screened in A375 cell lysates using the ATP-based probe at 5 μM. IC50 values are reported in micromolar units. Cell pellets are resuspended in four volumes of lysis buffer [25 mM Tris pH 7.6, 150 mM NaCl, 1% CHAPS, 1% Tergitol NP-40 type, 1% v/v phosphatase inhibitor cocktail II], sonicated using a tip sonicator, and dounce homogenized. Lysates are cleared by centrifugation at 100,000 g for 30 min. The cleared lysates are filtered through a 0.22 μM syringe filter, and gel filtered into reaction buffer [20 mM Hepes pH 7.8, 150 mM NaCl, 0.1% triton X-100, 1% v/v phosphatase inhibitor cocktail II]. MnCl2 is then added to the lysate to a final concentration of 20 mM prior to inhibitor treatment and probe labeling. Final inhibitor concentrations used for IC50 determinations are 10, 1, 0.1, and 0.01 μM. ATP competition experiments are performed at 1,000, 100, 10, and 1 μM ATP. All inhibitor treatments are performed at room temperature. |
| 動(dòng)物實(shí)驗(yàn) | Animal Models: Female NIH nude rats bearing BRAF V600E ST019VR PDX tumorsFormulation: 20% cyclodextrin, 25 mM phosphate, pH2.0Dosages: 30 mg/kgAdministration: p.o.[1] |
| 體外活性 | LY3009120抑制A375細(xì)胞和HCT116細(xì)胞的生長(zhǎng)，其IC50分別為9.2 μM和220 μM。同時(shí)，LY3009120也對(duì)酪氨酸激酶KDR有抑制作用，其IC50為3.9 μM。[1] |
| 體內(nèi)活性 | 在攜帶BRAF V600E ST019VR PDX腫瘤的大鼠中，LY3009120 (15或30 mg/kg, p.o.)表現(xiàn)出劑量依賴性的腫瘤生長(zhǎng)抑制效果。在裸鼠植入A375異種移植瘤中，單次口服LY3009120 (3到50 mg/kg, p.o.)顯示出對(duì)磷酸化ERK的劑量依賴性抑制，其中抑制磷酸化ERK 50%所需劑量(EC50)為4.36 mg/kg，達(dá)到抑制磷酸化ERK 50%的血漿濃度(EC50)為68.9 ng/mL或165 nM。[1] |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 10 mg/mL (23.56 mM)
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| 關(guān)鍵字 | Raf kinases | LY3009120 | DP 4978 | inhibit | Autophagy | LY 3009120 | LY-3009120 | Raf | DP4978 | Inhibitor |
| 相關(guān)產(chǎn)品 | Guanidine hydrochloride | Naringin | Valproic Acid | Taurine | Gefitinib | Aceglutamide | Hydroxychloroquine | Curcumin | Stavudine | Salicylic acid | Paeonol | Sodium 4-phenylbutyrate |
| 相關(guān)庫(kù) | 抗癌活性化合物庫(kù) | 經(jīng)典已知活性庫(kù) | 已知活性化合物庫(kù) | 激酶抑制劑庫(kù) | 抗衰老化合物庫(kù) | 酪氨酸激酶分子庫(kù) | 疼痛相關(guān)化合物庫(kù) | 藥物功能重定位化合物庫(kù) | 抗癌臨床化合物庫(kù) | 抗癌藥物庫(kù) |