AZD2858
目录号 : KM9458 CAS No. : 486424-20-8 纯度 : 98%

AZD2858 是一种有效的,可口服的 GSK-3 抑制剂,可以抑制 GSK-3α 和 GSK-3β 的活性,IC50 值分别为 0.9 和 5 nM,可用于骨折愈合的研究。

规格 价格 是否有货 数量
10mg
In-stock
50mg
In-stock
100mg 询价 In-stock
200mg 询价 In-stock

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生物活性

AZD2858 is a potent, orally active GSK-3 inhibitor, with IC50s of 0.9 and 5 nM for GSK-3α and GSK-3β, respectively, used in the research of fracture healing.

体外研究

AZD2858 (1 μM) increases β-catenin levels after a short period of time in human osteoblast cells. AZD2858 inhibits GSK-3β dependent phosphorylation with an IC50 of 68 nM. AZD2858 (10 nM) has no effect on β-catenin levels. AZD2858 increases TAZ expression and osterix expression both by 1.4-fold, with EC50 of 440 nM and 1.2 μM, respectively, in hADSC. AZD2858 also induces a marked increase in osteogenic mineralisation in hADSC. AZD2858 (AR28) demonstrates from 70- to greater than 6000-fold selectivity over a panel of other kinases and an IC50 of 5 nM. AR28 inhibits GSK-3 in murine cells and indicates activation of the canonical Wnt/β-catenin signaling cascade. AR28 (50, 10, and 1 nM) enhances the clonogenic ability of mesenchymal progenitors with osteogenic and adipogenic potential. AR28 (50 µM) also enhances the differentiation ability of mesenchymal progenitors to the osteogenic but not adipogenic lineage in vitro.

体内研究

AZD2858 (20 mg/kg) causes a dose-dependent increase in trabecular bone mass compared to control after a two-week treatment with a maximum effect. AZD2858 exhibits a substantial effect on fracture healing. AZD2858 (20 mg/kg) causes an increase in cortical BMC of 9%, cortical area of 10%, and cortical thickness of 11% at 3 weeks in the non-operated right femur of rats. AZD2858 (30 μmol/kg/day) alters the biomarkers of bone turnover with statistically significant increases in P1NP and decreases in TRAcP-5b seen from 3 days of treatment and onwards. AZD2858 demonstrates significant changes in serum bone turnover markers (P1NP and TRAcP-5b) and femur bone formation after only 7 days of daily dosing. AZD2858 (AR28, 30 mg/kg, s.c.) stimulates an increase in an initial wave of mesenchymal progenitors with osteogenic and adipogenic potential and drives their differentiation to the osteogenic lineage in BALB/c mice. AR28 (30 mg/kg, s.c.) enhances the proliferation of committed hematopoietic progenitors and their differentiation to the osteoclast lineage but does not prevent an overall increase in bone mass.

分子式
C21H23N7O3S
分子量
453.52
CAS号
486424-20-8
运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : 12.5 mg/mL (27.56 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.2050 mL 11.0249 mL 22.0497 mL
5 mM 0.4410 mL 2.2050 mL 4.4099 mL
10 mM 0.2205 mL 1.1025 mL 2.2050 mL
*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。
储备液的保存方式和期限:-80°C, 6 months; -20°C, 1 month。-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂:

——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂: 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: 1.25 mg/mL (2.76 mM); Suspended solution; Need ultrasonic

    此方案可获得 1.25 mg/mL (2.76 mM) 的均匀悬浊液,悬浊液可用于口服和腹腔注射。

    以 1 mL 工作液为例,取 100 μL 12.5 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

  • 2.

    请依序添加每种溶剂: 10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 1.25 mg/mL (2.76 mM); Clear solution

    此方案可获得 ≥ 1.25 mg/mL (2.76 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 12.5 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。

科研文献
The molarity calculator equation
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
The dilution calculator equation
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2
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