MK-2206 2HCl
目录号：S1078
Molecular Weight(MW): 480.39
MK-2206 2HCl是一种高度选择性的Akt1/2/3抑制剂，在无细胞试验中IC50分别为8 nM/12 nM/65 nM；对250种其他蛋白激酶没有抑制活性。Phase 2。
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客户使用该产品的21个实验数据：
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Inhibition of AKT signaling abolishes MKK4 phosphorylation on Ser78 in injured axons. Cultures of sensory neurons were treated with 5 µM MK-2206 or 5 µM GDC-0068 for 1 hr prior to axotomy. Axonal proteins harvested at indicated time points after axotomy were subjected to immunoblot analysis.
Cell, 2015, 160(1-2): 161-76 . MK-2206 2HCl purchased from Selleck.
j,k, Gene expression ofMYOCD (j) and ACTA2 ( SMA, k) after applying inhibitors of key components involved in the DDR2 downstream signalling pathway to HSCs cultured within 3D collagen matrix subjected to stretching (ST) (n=3, one-way ANOVA, **P=0.0036, ****P<0.0001). l,m, Expression of SMA was significantly reduced after treatment with related inhibitors in early-stage FμNs. (n=4, one-way ANOVA, ***P=0.001, ****P<0.0001). AKT-i: MK-2206
Nature Materials, 2017, 16:1252-1261.. MK-2206 2HCl purchased from Selleck.
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The PI3K or AKT inhibition does not restore sensitivity to WZ4002 in PC9 WZR. PC9GR4 or WZR10 cells were treated with WZ4002 alone at the indicated concentrations or in combination with the AKT inhibitor MK-2206 (1 uM). MK-2206 effectively inhibited AKT in both cells.
Cancer Discov 2012 2, 934-47. MK-2206 2HCl purchased from Selleck.
Cancer Cell 2013 24, 766-76. MK-2206 2HCl purchased from Selleck.
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VE-cadherin-induced Akt activation mediates YAP phosphorylation and translocation in ECs. HUVECs were starved for 1h and treated with thrombin (1U) for 1h. Total cell lysates were probed with anti-pAkt, Akt or b-actin antibody. The representative blots of three independent experiments are depicted, and the normalized values for p-Akt are shown. HUVECs were cultured and starved as described as in d and incubated for 8h in complete medium with the Akt inhibitor, MK-2206 (1 uM). pAkt, Akt, pYAP and YAP were detected by western blotting using specific antibodies.
Nat Commun 2015 6:6943. MK-2206 2HCl purchased from Selleck.
Rap1b negatively regulates neutrophil transcellular migration by limiting PI3K-Akt signaling. (A-D) Effect of Akt inhibitor MK2206 (2 uM), Src inhibitor PP2 (10 uM), or vehicle control (DMSO) on WT or Rap1b-/- neutrophil functions. (A) Percentage of neutrophil transendothelial migration in 3D migration model. (B) ECM degradation assessed on Oregon green-labeled gelatin matrix; (left) representative images on (bar, 10 um) and (right) bar graph is percentage of matrix degradation. (C) Percentage of cells forming multiple protrusions. (D) Percentage of neutrophils present at junction of activated bEND.3 in 3D migration assay. Mean ?SD; n = 3 independent experiments. **, P < 0.01; ***, P < 0.001; NS, not significant using unpaired Student's t test).
J Exp Med 2014 211(9), 1741-58. MK-2206 2HCl purchased from Selleck.
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Inhibitors of AKT or ERK overcome SDF-1a-mediated resistance to ibrutinib-triggered PARP and caspase 3 cleavage in CXCR4S338X-expressing BCWM.1 cells. CXCR4S338X-expressing WM cells were treated with ibrutinib (0.5 uM) alone or in the presence of SDF-1a (20 nM) and/or the AKT inhibitors MK-2206 (0.5 uM) and AZD-5363 (0.5 uM); or the MEK inhibitors AS-703026 (0.25 uM), AZD-6244 (0.5 uM) and UO126 (5.0 uM). (a) Immunoblotting results for phosphoAKT (S473) and phospho-ERK (T202/Y204) in CXCR4S338X-expressing BCWM.1 cells pretreated with ibrutinib with and without AKT or ERK inhibitors, then subjected to SDF-1a stimulation for 2 min. The inhibitory effect of AZD-5363 on AKT, which is known to paradoxically hyper-phosphorylate pAKT(S473) was confirmed by inhibition of the phospho-activity for the downstream AKT targets glycogen synthase kinase 3b and pS6. (b) Immunoblotting results for cleaved PARP and cleaved caspase 3 in CXCR4S338X-expressing BCWM.1 cells treated with ibrutinib and/or AKT or ERK inhibitors for 6 h at IC50 doses. GAPDH, glyceraldehyde 3-phosphate dehydrogenase.
Leukemia 2015 29(1), 169-76. MK-2206 2HCl purchased from Selleck.
Induction of apoptosis positively correlates with FOXO3a protein levels and phosphorylation. (a) Treatment of 11 cell lines seeded in 6-well plates with 8 μM MK-2206 or DMSO for 48 hours. Nuclei were harvested for PI staining and FACS analysis and the differences between drug and no drug are displayed as in Figure b. Both conditions were performed in triplo for each cell line. Below the FACS data is a we stern blot of cell lysates from this panel treated with 8 μM MK-2206 or DMSO and harvested at 24 hours. Each cell line name corresponds to the two western lanes below it and the four cell cycle bars above it.
Cancer Res 2013 73, 2189-98. MK-2206 2HCl purchased from Selleck.
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Mean IL-8 concentrations determined by ELISA of the supernatants of HeLa cells infected with wild-type Salmonella. Kinase inhibitors are indicated on the x axis, and the target families of the inhibitors are indicated above each column. CEC, chelerythrine; Pim Inh, Pim-1 inhibitor 2. Inhibitors that significantly affected IL-8 production relative to the control (P < 0.05, Bonferroni post hoc test from one-way ANOVA) are indicated with an asterisk. Relative cell viability is also shown, as determined by reduction of XTT by viable cells. A450, absorbance at 450 nm.
Sci Signal 2011 4, rs9. MK-2206 2HCl purchased from Selleck.
Reducing cellular levels of PtdIns5P by overexpression of PIP4Kα inhibits clonogenic growth of U2OS but enhances cell survival in response to H2O2 stimulation. A) U2OS cells (1000) were plated, allowed to attach overnight, and then treated with DMSO (control), PI-103 (0.5 μM), U0126 (5 μM), or SB203580 (5 μM) for 9 d. Cell colonies were stained using crystal violet. Dried plates were scanned. Representative results are shown. B) U2OS cells (1000) were plated, allowed to attach overnight, and then treated with DMSO (control), MK-2206 (1 μM), triciribine (1 μM), KU0063794 (1 μM), or PI-103 (0.5 μM) for 9 d. Cell colonies were stained using crystal violet. Dried plates were scanned. Representative results are shown.
FASEB J 2013 27, 1644-56. MK-2206 2HCl purchased from Selleck.
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A. Western blot analysis of pAKT activation in ovarian cancer cell lines treated with exogenous IGF-1. B. Activation of pAKT by IGF-1 in low-grade ovarian cancer cell lines was blocked by the AKT inhibitor MK-2206 in a dose-dependent manner.
Gynecol Oncol 2011 123, 13-8. MK-2206 2HCl purchased from Selleck.
Comparative effects of inhibitors by immunofluorescence microscopy study. Confluent HC11 cells were grown on poly-L-lysine-coated glass coverslips (immunofluorescence) and on plastic plates (biochemical control) and then treated with inhibitors according to the standard procedure. Upper part: the biochemical action of the inhibitors was tested to validate the immunofluorescence results. Cellular proteins were analyzed by SDS-PAGE and the immunoblots were successively probed with anti-ADRP, anti-β-casein, and anti- β-actin antibodies and their respective HRP-conjugated secondary antibodies. Each experimental condition was performed in duplicate. Lower part: cells were fixed, permeabilized and subjected to immunofluorescence microscopy using antiserum against ADRP and TRITC-conjugated secondary antibody (red).
Biochim Biophys Acta 2012 1823, 987-96. MK-2206 2HCl purchased from Selleck.
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Confocal microscopy images of NO formation. DAF 2 DA-loaded washed platelets (1.0109 platelets/mL) were preincubated at 378C with saline (A), and then stimulated for 1min with 0.1 (B), 1.0 (C) or 10 (D) μM AEA. In Panel (E-F-G) washed platelets were preincubated with 1 μM SR1 (E), 1 Mm MK2206 (F) or 20 μM LY294002 (G), and then stimulated for 1min with 1.0 μM AEA. In panel (H) is reported the effect of 5 mg/mL collagen, used as a positive control. All the experiments were carried out in the presence of 100 μM L-arginine. NO formation was visualized by confocal microscropy as detailed in Methods.
J Cell Biochem 2011 112, 924–932. MK-2206 2HCl purchased from Selleck.
The AEA effect on eNOS phosphorylation. Washed platelets (1.0109 platelets/mL), preincubated at 378C with saline, 1 μM SR1, 1 μM SR2, 20 μM LY294002, 1 μM MK2206, 1.0 μM EGTA, or 30 μM BAPTA/AM, were stimulated for 1 min with 1.0 μM AEA. At the end of incubation suitable aliquots were immunoblotted with anti-p-eNOSser1177 as detailed in Methods.Blots are representative of five independent experiments.
J Cell Biochem 2011 112, 924–932. MK-2206 2HCl purchased from Selleck.
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Effect of selected agents on NOx and cGMP formation induced by AEA. Washed platelets (1.0109 platelets/mL), prewarmed at 378C with saline or 1mM SR1, 1 μM SR2, 20 μM URB597 (URB), 1 μM MK2206 (MK) or 20 μM LY294002 (LY), were incubated for 1min with 100 μM L-arginine in the presence of 1.0 μM AEA. NOx (panel A) and cGMP (panel B) content were determined as detailed in Methods. Each bar represents the meanSD of five independent experiments carried out in triplicate. Student,s t-test: P <0.0001 versus none;P <0.0005; P <0.005 versus AEA
J Cell Biochem 2011 112, 924–932. MK-2206 2HCl purchased from Selleck.
C.U87MG cells were treated with vehicle or 1 μM MK-2206 for 1 hr, and then irradiated with 6 Gy. Total cell lysate was harvested 1 hr after IR and subjected to Western blot analysis with the indicated antibody. Cells without IR treatment were used as a control.
D. Cells were treated with vehicle (control) or 1 μM MK-2206 for 1 hr, then irradiated with indicated dosage. 4 hr after IR, cells were fed with drug-free medium, and incubated for another 20 hr at 37°C, after which they were trypsinized and seeded for clonogenic survival assay. Colony-forming efficiency was determined 14 d later.Radiat Oncol 2009 4, 43. MK-2206 2HCl purchased from Selleck.
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(B) Dose-response curves for DIPG 4 and SF7761 cells treated with the small molecule AKT inhibitor MK-2206 (error bars represent SEM).
Oncol Rep, 2018, 39(2):455-464. MK-2206 2HCl purchased from Selleck.
MK-2206 2HCL inhibited the sorafenib-induced PI3K/mTOR pathway activation and enhanced the cytotoxic effects of sorafenib in resistant cell lines. (A) HUH-7 hepatoma cells treated with sorafenib (5 μM) for 24 h with or without pretreatment with specific kinase inhibitors (MK-2206 2HCL, 15 μM). The expressions of p-AKT and cleaved PARP were revealed by Western blotting. (B) SK-HEP-1 hepatoma cells treated with sorafenib (5 μM) for 24 h with or without pretreatment with specific kinase inhibitors (MK-2206 2HCL, 15 μM). The expressions of p-AKT and cleaved RARP were revealed by Western blotting. (C) HUH-7 hepatoma cells treated with sorafenib (5 μM) with or without the kinase inhibitors for 24 h. The proportions of apoptotic cells were evaluated by annexin V labeling. (D) SK-HEP-1 hepatoma cells treated with sorafenib (5 μM) with or without the kinase inhibitors for 24 h. The proportions of apoptotic cells were evaluated by annexin V labeling. (*P < 0.05, HUH-7, SK-HEP-1 are control groups, R-HUH-7, R-SK-HEP-1 are resistant groups).
J Surg Res, 2016, 206(2):371-379. MK-2206 2HCl purchased from Selleck.
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After starved in serum-free medium for 24h, Breast cancer cells incubated with the indicated concentrations of MK-2206 for 3h,followed by 15-minute stimolation of 100ng/ml EGF.
Dr. Zhang of Tianjin Medical University. MK-2206 2HCl purchased from Selleck.
IC50 values for an Akt inhibitor (MK-2206) and a MEK inhibitor (U0126) in a panel of mouse and human anaplastic (ATC) and follicular (FTC) carcinoma cell lines. On the bottom, a Western blotting showing the effect on the activation of Akt and ERK1/2 of one hour exposure to these inhibitors (MK-2206: 500 nM, U0126: 10 μM).
Oncotarget 2011 2, 1109-26. MK-2206 2HCl purchased from Selleck.
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PI3K pathway signaling in GDC-0941 and MK-2206 treated MCF-7 derivatives with PIK3CA or AKT1 mutations. Cells were grown in medium containing 5% FBS and treated with vehicle or increasing concentrations of GDC-0941 (0 nM, 50 nM, 100 nM, and 400 nM) or MK-2206 (0 nM, 100 nM, 250 nM, 1000 nM). After 24 hours of drug treatment, lysates were prepared and equal amounts of protein were load ed onto SDS-PAGE gels and blotted with the indicated antibodies.
MK-2206 2HCl purchased from Selleck.
产品安全说明书
Akt抑制剂选择性比较
生物活性
| 产品描述 | MK-2206 2HCl是一种高度选择性的Akt1/2/3抑制剂，在无细胞试验中IC50分别为8 nM/12 nM/65 nM；对250种其他蛋白激酶没有抑制活性。Phase 2。 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 特性 | MK-2206是第一个进入临床研究阶段的Akt小分子变构抑制剂。 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 靶点 |
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| 体外研究 |
MK-2206是变构抑制剂，由pleckstrin同源结构域激活。MK-2206抑制Akt的苏氨酸308位点和丝氨酸473位点的自身磷酸化作用。另外，MK-2206阻止Akt调节的下游信号分子（包括TSC2, PRAS40，及核糖体S6蛋白）的磷酸化作用。与抑制Ras 突变型细胞系(如NCI-H358, NCI-H23, NCI-H1299, 和Calu-6)相比，MK-2206 更有效地抑制Ras野生型细胞系(如A431, HCC827, 和NCI-H292)。MK-2206和细胞毒素药剂如erlotinib 和lapatinib联用作用于肺部NCI-H460肿瘤细胞或者卵巢A2780肿瘤细胞，MK-2206也显示出协同效应。[1] |
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| Cell Data |
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| 体内研究 | MK-2206和这些细胞毒素药剂联用作用于NCI-H292移植瘤，MK-2206显示出非常有效的抗癌活性。卵巢癌A2780移植瘤中，按动物体重，每千克处理240mg MK-2206,则可抑制70%以上的Akt1/2在苏氨酸308位点和丝氨酸473位点的磷酸化，导致肿瘤生长抑制率达到60%。[1] |
推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)
| 激酶实验： |
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Akt激酶实验: 通过得到的GSK 生物素肽段基质测定Akt激酶。使用含镧系金属螯合物偶联单抗的均相时间分辨荧光(HTRF)测定肽段磷酸化程度，这种单抗专门作用于与链霉亲和素——藻蓝素(SA-APC)载体相结合的磷酸化作用，SA-APC载体可以结合到肽段的部分生物素上。当镧系金属螯合物与藻蓝素相接触时，无辐射的能量从镧系金属螯合物传递给藻蓝素，然后藻蓝素发射波值为655纳米的光线。工作液:100X 蛋白酶抑制剂混合物(PIC)：1mg/ml苯甲脒，0.5 mg/ml 抑肽素, 0.5 mg/ml亮抑肽酶, 0.5 mg/ml 抑肽酶。10X实验 buffer: 500 mM HEPES（pH 为7.5）, 1% PEG, 16.6 mM EDTA, 1 mM EGTA, 1% BSA, 20 mM 9-甘油磷酸。抑制 buffer：50 mM HEPES（pH为7.3）, 16.6 mM EDTA, 0.1% BSA, 0.1% Triton X-100, 0.17 nM 标记的单抗, 0.0067mg/ml SA-APC。ATP/MgCl2工作液: 1X 实验buffer, 1 mM DTT, 1X PIC, 5% 甘油, 激活的Akt。肽段工作液：1X实验buffer, 1 mM DTT, 1X PIC, 5% 甘油 2 TM GSK生物素肽段。工作液加到合适的孔中，然后加入总负荷为16的 ATP/MgCl2，反应开始。含MK-2206的实验组和对照组加入总负荷为10的肽段工作液。然后加入总负荷为13的酶液，混匀。反应进行50分钟，然后加入总负荷为60的均相时间分辨荧光抑制buffer停止反应。阻断的反应在室温下温育30分钟以上，然后使用仪器读数。 |
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| 细胞实验： |
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| 动物实验： |
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溶解度 (25°C)
| 体外 | DMSO | 14 mg/mL (29.14 mM) |
|---|---|---|
| Water | Insoluble | |
| Ethanol | Insoluble | |
| 体内 |
从左到右依次将纯溶剂加入产品，现配现用(数据来自Selleck实验检测而非文献)： 15% Captisol |
17 mg/mL |
* 溶解度检测是由Selleck技术部门检测的，可能会和文献中提供的溶解度有所差异，这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。
化学数据
| 分子量 | 480.39 |
|---|---|
| 化学式 | C25H21N5O.2HCl |
| CAS号 | 1032350-13-2 |
| 稳定性 | powder |
| in solvent | |
| 别名 | N/A |
计算器
摩尔浓度计算器
本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为:
质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)
摩尔浓度计算公式
*在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。
稀释计算器
用本工具协助配置特定浓度的溶液，使用的计算公式为：
开始浓度 x 开始体积 = 最终浓度 x 最终体积
稀释公式
稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )
在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。.
分子量计算器
通过输入化合物的化学式来计算其分子量：
注：化学分子式大小写敏感。C10H16N2O2 c10h16n2o2
摩尔浓度计算器
临床试验信息
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01263145 | Completed | Adult Solid Neoplasm|Recurrent Breast Carcinoma|Stage IV Breast Cancer | National Cancer Institute (NCI) | January 5 2011 | Phase 1 |
| NCT01239342 | Active not recruiting | Metastatic Renal Cell Cancer|Recurrent Renal Cell Carcinoma|Stage IV Renal Cell Cancer | National Cancer Institute (NCI)|M.D. Anderson Cancer Center | January 27 2011 | Phase 2 |
| NCT01306045 | Recruiting | Carcinoma Non-Small-Cell Lung|Carcinoma Small Cell Lung|Carcinoma Thymic | National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) | February 26 2011 | Phase 2 |
| NCT01604772 | Completed | Recurrent Oral Cavity Adenoid Cystic Carcinoma|Recurrent Salivary Gland Carcinoma|Salivary Gland Adenoid Cystic Carcinoma|Stage IVA Major Salivary Gland Cancer AJCC v7|Stage IVA Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7|Stage IVB Major Salivary Gland Cancer AJCC v7|Stage IVB Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7|Stage IVC Major Salivary Gland Cancer AJCC v7|Stage IVC Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7 | National Cancer Institute (NCI) | July 23 2012 | Phase 2 |
| NCT01480154 | Active not recruiting | Adult Solid Neoplasm|Hormone-Resistant Prostate Carcinoma|Recurrent Melanoma|Recurrent Prostate Carcinoma|Recurrent Renal Cell Carcinoma|Stage IIIA Cutaneous Melanoma AJCC v7|Stage IIIB Cutaneous Melanoma AJCC v7|Stage IIIC Cutaneous Melanoma AJCC v7|Stage IV Cutaneous Melanoma AJCC v6 and v7|Stage IV Prostate Cancer AJCC v7|Stage IV Renal Cell Cancer AJCC v7 | National Cancer Institute (NCI) | November 23 2011 | Phase 1 |
| NCT01251861 | Active not recruiting | Recurrent Prostate Carcinoma|Stage I Prostate Cancer AJCC v7|Stage IIA Prostate Cancer AJCC v7|Stage IIB Prostate Cancer AJCC v7|Stage III Prostate Cancer AJCC v7 | National Cancer Institute (NCI) | December 23 2010 | Phase 2 |
技术支持
在订购、运输、储存和使用我们的产品的任何阶段，您遇到的任何问题，均可以通过拨打我们的热线电话400-668-6834，或者技术支持邮箱tech@selleck.cn，直接联系到我们。我们会在24小时内尽快联系您。
如果有其他问题，请给我们留言。
常见问题及建议解决方法
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问题 1：
What is your recommendation for preparing the solution and how would you deliver it to the mice (i.p. or gavage)?
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回答：
You can resuspend MK-2206 in 15% Captisol at up to 17mg/ml. It's a suspension and is for oral gavage use only.
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问题 2：
I would want to know if MK-2206 could cross the blood brain barrier?
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回答：
MK-2206 can cross BBB based on the following reference: https://clinicaltrials.gov/ct2/show/NCT01249105.
