XMD8-92
(Synonyms: 2-[[2-乙氧基-4-(4-羟基-1-哌啶基)苯基]氨基]-5,11-二氢-5,11-二甲基-6H-嘧啶并[4,5-B][1,4]苯并二氮杂卓-6-酮) 目录号 : GC11076
XMD8-92是一种BMK1激酶抑制剂，IC50为1.5µM，解离常数（Kd）为80nM。
Cas No.:1234480-50-2
Sample solution is provided at 25 µL, 10mM.
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XMD8-92 is a BMK1 kinase inhibitor, with an IC50 of 1.5μM and a dissociation constant (Kd) of 80nM[1].
In vitro, XMD8-92 (0, 0.78, 1.56, 3.13, 6.25, 12.50 and 25µM; 48h) inhibits the proliferation of AsPC-1 cancer cells in a dose-dependent manner[2]. XMD8-92 (10µM; 1h) treatment prevents epidermal growth factor (EGF) or hypoxia-induced migration of hepatocellular carcinoma (HCC) cells and induces cytoskeletal remodeling[3].
In vivo, XMD8-92 (50mg/kg/twice a day; 28 days; i.p.) significantly inhibited the growth of tumors in xenografted mice[1]. XMD8-92 (50mk/kg; 15 days; i.p.) inhibits pancreatic tumor xenograft growth via a DCLK1-dependent mechanism[2]. Treatment with XMD8-92 (10mg/kg; once per week; s.c.) significantly reduced retinal inflammation, VEGF production, and oxidative stress in diabetic mice[4].
References:
[1] Yang Q, Deng X, Lu B, et al. Pharmacological inhibition of BMK1 suppresses tumor growth through promyelocytic leukemia protein. Cancer Cell. 2010 Sep 14;18(3):258-67.
[2] Sureban SM, May R, Weygant N, et al. XMD8-92 inhibits pancreatic tumor xenograft growth via a DCLK1-dependent mechanism. Cancer Lett. 2014 Aug 28;351(1):151-61.
[3] Rovida E, Di Maira G, Tusa I, et al. The mitogen-activated protein kinase ERK5 regulates the development and growth of hepatocellular carcinoma. Gut. 2015 Sep;64(9):1454-65.
[4] Howell SJ, Lee CA, Batoki JC, et al. Retinal Inflammation, Oxidative Stress, and Vascular Impairment Is Ablated in Diabetic Mice Receiving XMD8-92 Treatment. Front Pharmacol. 2021 Aug 11;12:732630.
XMD8-92是一种BMK1激酶抑制剂，IC50为1.5µM，解离常数（Kd）为80nM[1]。
在体外实验中，在体外，XMD8-92（0, 0.78, 1.56, 3.13, 6.25, 12.50和25µM; 48h）能以剂量依赖性方式抑制AsPC-1癌细胞的增殖[2]。XMD8-92（10µM; 1h）处理可阻止表皮生长因子（EGF）或缺氧诱导的肝细胞癌（HCC）细胞迁移，并诱导细胞骨架重塑[3] 。
在体内实验中，XMD8-92（50mg/kg/一天两次; 28天; i.p.）显著抑制了异种移植小鼠中肿瘤的生长[1]。XMD8-92（50mg/kg; 15天; i.p.）通过DCLK1依赖性机制抑制胰腺肿瘤异种移植生长[2]。XMD8-92（10mg/kg; 每周一次; s.c.）处理显著减轻了糖尿病小鼠的视网膜炎症、VEGF产生和氧化应激[4]。
| Cell experiment [1]: | |
Cell lines | AsPC-1 cancer cells |
Preparation Method | AsPC-1 cancer cells were seeded into a 96-well cell culture plate at a density of 1×10⁴ cells per well, with three replicate wells per group. The cells were cultured in medium containing XMD8-92, with DMSO as the vehicle, at concentrations of 0, 0.78, 1.56, 3.13, 6.25, 12.50 and 25µM. After 48h of treatment, 10µl of TACS MTT reagent was added to each well, and the cells were incubated at 37℃ until a dark crystalline precipitate formed within the cells. Subsequently, 100µl of a 266mM NH4OH solution in DMSO was added to each well, and the plate was placed on a low-speed shaker for 1min. After shaking, the plate was incubated for 10min in the dark, and the OD550 value for each well was read using a microplate reader. The results were averaged and expressed as a percentage of the DMSO (vehicle) control group, along with the standard error of the mean. |
Reaction Conditions | 0, 0.78, 1.56, 3.13, 6.25, 12.50 and 25µM; 48h |
Applications | XMD8-92 inhibits the proliferation of AsPC-1 cancer cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | 6-week-old NOD/SCID mice |
Preparation Method | Five hundred thousand (5×10⁵) HeLa cells were resuspended in DMEM medium and injected subcutaneously into the right flank of 6-week-old NOD/SCID mice on day 0. On the second day (day 1) after tumor cell injection, the mice were randomized into two groups: one group of 6 mice for the XMD8-92 (1-28 days) group and another group of 18 mice for the control group. The XMD8-92 (1-28 days) group received XMD8-92 at a dose of 50mg/kg via intraperitoneal injection twice daily. The control group received daily injections of the vehicle solution as a control. On day 7, the control group was further randomized into two groups: one group of 6 mice for the XMD8-92 (7-28 days) group and another group of 12 mice that continued as the control group. On day 14, the remaining control group was again randomized into two groups: one group of 6 mice for the XMD8-92 (14-28 days) group and another group of 6 mice that continued as the control group. Treatment with XMD8-92 for the XMD8-92 (7-28 days) and XMD8-92 (14-28 days) groups began on day 7 and day 14, respectively. Tumor size was measured using a caliper, and tumor volume was calculated using the formula: L×W²×0.52, where L is the longest diameter and W is the shortest diameter. |
Dosage form | 50mg/kg/twice a day; 28 days; i.p. |
Applications | XMD8-92 significantly inhibited the growth of tumors in xenografted mice. |
References: | |
| Cas No. | 1234480-50-2 | SDF | |
| 别名 | 2-[[2-乙氧基-4-(4-羟基-1-哌啶基)苯基]氨基]-5,11-二氢-5,11-二甲基-6H-嘧啶并[4,5-B][1,4]苯并二氮杂卓-6-酮 | ||
| 化学名 | 2-[2-ethoxy-4-(4-hydroxypiperidin-1-yl)anilino]-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one | ||
| Canonical SMILES | CCOC1=C(C=CC(=C1)N2CCC(CC2)O)NC3=NC=C4C(=N3)N(C5=CC=CC=C5C(=O)N4C)C | ||
| 分子式 | C26H30N6O3 | 分子量 | 474.57 |
| 溶解度 | ≥ 23.75 mg/mL in DMSO | 储存条件 | Store at 4°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1072 mL | 10.5359 mL | 21.0717 mL |
| 5 mM | 421.4 μL | 2.1072 mL | 4.2143 mL |
| 10 mM | 210.7 μL | 1.0536 mL | 2.1072 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >98.00%
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