化合物 Milciclib|T6081|TargetMol

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價(jià)格	￥525	￥1530	￥2260
包裝	1mg	5mg	10mg

最小起訂量	1mg
發(fā)貨地	上海
更新日期	2025-07-28

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產(chǎn)品詳情

中文名稱:化合物 Milciclib	英文名稱:Milciclib
CAS:802539-81-7	品牌: TargetMol
產(chǎn)地: 美國(guó)	保存條件: Powder: -20°C for 3 years \| In solvent: -80°C for 1 year \| Shipping with blue ice/Shipping at ambient temperature.
純度規(guī)格: 99.73%	產(chǎn)品類別: 抑制劑
貨號(hào): T6081

Product Introduction

Bioactivity

名稱	Milciclib
描述	Milciclib (PHA-848125) (PHA-848125) is a potent, ATP-competitive CDK inhibitor for CDK2 with IC50 of 45 nM. It is >3-fold more selective for CDK2 than CDK1, 2, 4, 5, and 7. Phase 2.
細(xì)胞實(shí)驗(yàn)	Melanoma cells are suspended in culture media at a concentration of 2 × 104 cells/mL, dispensed in 50 μL aliquots into flat-bottom 96-well plates and allowed to adhere overnight at 37 °C. Graded amounts of PHA-848125 or TMZ are then added to the wells (4 wells per point) in 50 μL of CM and the plates are incubated at 37 °C in a 5% CO2 humidified atmosphere for 5 days. The cytotoxic effects of TMZ are also evaluated in combination with the MGMT inhibitor BG. To this end, 10 μM BG is added to the plates 2 hours before TMZ and left in culture for the entire period of cell exposure to the drug. ContS1017rol groups are represented by untreated cells and cells treated with BG or DMSO alone. The growth of the cells treated with BG or DMSO alone does not differ from that of untreated cells. MGMT activity of BG-treated cells is undetectable 2 hours after the addition of the inhibitor PHA-848125 and remained essentially undetectable up to the end of the assay. Normal melanocytes are suspended in MGM at the concentration of 1.6 × 105 cells/mL, plated (50 μL/well) and exposed to TMZ + BG or to PHA-848125 as described for melanoma cells. At the end of the incubation period, cell growth is evaluated by the MTT assay. Briefly, 0.1 mg of MTT (in 20 μL of PBS) is added to each well and cells are incubated at 37 °C for 4 hours. Cells are then lysed with a buffer (0.1 mL/well) containing 20% SDS and 50% N,N-dimethylformamide, pH 4.7. After overnight incubation, the absorbance is read at 595 nm using a 3550-UV microplate reader. Cell sensitivity to drug treatment is expressed in terms of IC50 (drug concentration producing 50% inhibition of cell growth, calculated on the regression line in which absorbance values at 595 nm are plotted against the logarithm of drug concentration).(Only for Reference)
激酶實(shí)驗(yàn)	Biochemical kinase inhibition assays: Inhibition of kinase activity by PHA-848125 is assessed using a strong anion exchanger (Dowex 1X8 resin)–based assay in robotized format run on 384-well plates. In this assay, specific peptides or protein substrates are transphosphorylated by their specific kinase in the presence of ATP traced with [γ-33P]ATP using optimal buffers and cofactors. The potency of PHA-848125 toward CDKs and 38 additional kinases belonging to an in-house Kinase Selectivity Screening panel is evaluated, and the relevant IC50s are determined. For each enzyme, the absolute KM values for ATP and the specific substrate are calculated and each assay is then run at optimized ATP (2KM) and substrate (5KM) concentrations. This setting enables direct comparison of IC50 values of PHA-848125 across the panel for evaluation of its biochemical profile.
體外活性	Milciclib以較低的效能抑制cyclin H/CDK7、cyclin D1/CDK4、p35/CDK5以及cyclin E/CDK2和cyclin B/CDK1的活性，其IC50值分別為0.15、0.16、0.265、0.363、0.398 μM。[1] Thropomyosin受體激酶A也在與CDKs相同的nM范圍內(nèi)被Milciclib抑制。在最敏感的Milciclib細(xì)胞系中，Milciclib引起濃度依賴性的G(1)階段阻滯。[2]Milciclib還干擾了在CDK2和CDK4特異性位點(diǎn)上視網(wǎng)膜母細(xì)胞瘤蛋白的磷酸化，降低了視網(wǎng)膜母細(xì)胞瘤蛋白和cyclin A的水平，并提高了p21(Cip1)、p27(Kip1)和p53的表達(dá)。在添加TMZ后48小時(shí)將Milciclib加入細(xì)胞，之后再培養(yǎng)3天評(píng)估細(xì)胞生長(zhǎng)。[2] TMZ、BG和Milciclib的化合物組合根據(jù)細(xì)胞系的不同，對(duì)細(xì)胞生長(zhǎng)產(chǎn)生加和作用或協(xié)同作用。[2] 在沒有BG的情況下，該組合在對(duì)TMZ中等敏感的細(xì)胞系中比單獨(dú)化合物更活躍，但與僅用Milciclib治療的兩個(gè)TMZ抗性細(xì)胞系效果類似。當(dāng)TMZ和BG與Milciclib聯(lián)合使用針對(duì)培養(yǎng)的正常黑素細(xì)胞時(shí)，并未觀察到協(xié)同或加和的抗增殖效應(yīng)。[2]
體內(nèi)活性	在臨床前異種移植的A2780人類卵巢癌模型中，Milciclib展現(xiàn)了良好的療效并在連續(xù)日常治療中表現(xiàn)出良好的耐受性。對(duì)K-Ras(G12D)LA2小鼠用Milciclib處理（每日兩次，每次40 mg/kg，持續(xù)10天），在治療結(jié)束時(shí)顯著抑制了腫瘤生長(zhǎng)，并伴隨著細(xì)胞膜周轉(zhuǎn)的減少。[3] 另一方面，經(jīng)口給藥后，Milciclib在多種人源異種移植物、致癌誘導(dǎo)的腫瘤以及分散性原發(fā)性白血病模型中顯示出顯著的抗腫瘤活性；嚙齒動(dòng)物的血漿濃度與抑制癌細(xì)胞增殖的濃度處于相同范圍內(nèi)。[4]
存儲(chǔ)條件	Powder: -20°C for 3 years \| In solvent: -80°C for 1 year \| Shipping with blue ice/Shipping at ambient temperature.
溶解度	H2O : < 1 mg/mL (insoluble or slightly soluble) Ethanol : < 1 mg/mL (insoluble or slightly soluble) DMSO : 85 mg/mL (184.55 mM), Sonication is recommended.
關(guān)鍵字	Trkreceptor \| TrkA \| Trk receptor \| PHA848125 \| PHA 848125 \| Milciclib \| Inhibitor \| inhibit \| Cyclin dependent kinase \| CDK7/CyclinH \| CDK5/p35 \| CDK4/CyclinD1 \| CDK2/CyclinA \| CDK \| Autophagy
相關(guān)產(chǎn)品	Oxyresveratrol \| Guanidine hydrochloride \| Naringin \| Valproic Acid \| Taurine \| Gefitinib \| Aceglutamide \| Hydroxychloroquine \| Curcumin \| Stavudine \| Paeonol \| Sodium 4-phenylbutyrate
相關(guān)庫(kù)	抑制劑庫(kù) \| 經(jīng)典已知活性庫(kù) \| 抗癌活性化合物庫(kù) \| 已知活性化合物庫(kù) \| 臨床失敗化合物庫(kù) \| 激酶抑制劑庫(kù) \| 抗衰老化合物庫(kù) \| 膜蛋白靶向化合物庫(kù) \| 藥物功能重定位化合物庫(kù) \| 酪氨酸激酶分子庫(kù) \| 抗癌臨床化合物庫(kù) \| 抗癌藥物庫(kù)

關(guān)鍵字： PHA-848125|TargetMol

公司簡(jiǎn)介

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