Ulixertinib (hydrochloride)
(Synonyms: BVD-523盐酸盐,BVD-523,VRT-752271) 目录号 : GC11422
An ERK1/2 inhibitor
Cas No.:1956366-10-1
Sample solution is provided at 25 µL, 10mM.
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Ulixertinib, also named as BVD-523, is a novel and reversible inhibitor of ERK1/2. Ulixertinib potently and selectively inhibits the activity of ERK1 and ERK2 kinases in a reversible, ATP-competitive fashion [1].
The Ras-dependent extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein (MAP) kinase pathway plays a central role in cell proliferation control. In normal cells, sustained activation of ERK1/ERK2 is necessary for G1- to S-phase progression and is associated with induction of positive regulators of the cell cycle and inactivation of antiproliferative genes. The RAF-MEK-ERK1/2 signal pathway plays a dominant role in promoting cell survival [2].
In vitro: In two lymphoma cell lines (SUDHL-10 and Raji), treatment with ulixertinib significantly reduced the expression of ERK1/2 phosphorylation in a dose-dependent manner. Treatment with 0.4 nM ulixertinib decreased the percentage of G2-M phase cells in the SUDHL-10 cells. In the Raji cells, treated with ulixertinib at 0.4 and 1.0 nM increased the percentage of G0-G1 phase cells and decreased S phase cells [1]. Treatment of ulixertinib at the dose of 0.1, 0.4 and 1.0 nM for 48 h dose-dependently increased the number of early apoptotic SUDHL- 10 and Raji cells [1]. In SUDHL-10 and Raji cells, ulixertinib reduced mRNA and protein expression of VEGFR2 and Bcl-2 genes and increased the expression of Bax and caspase-3 genes [1].
In vivo: BVD-523 inhibited tumor growth in BRAF-mutant melanoma and colorectal xenografts as well as in KRAS-mutant colorectal and pancreatic models. BVD-523 treatment in combination with dabrafenib inhibited tumor growth in a BRAF-mutant melanoma model [3]. Single-agent BVD-523 inhibited the growth of a patient-derived tumor xenograft harboring cross-resistance to dabrafenib, trametinib, and the combination treatment following clinical progression on a MEK inhibitor [3].
Clinical trials: In patients (pts) with advanced solid tumors, BVD-523 (ulixertinib) achieved pharmacologically relevant exposure and manageable tolerability at its MTD of 600 mg twice a day [4].
References:
[1] Ding W J, Tao W P, Zeng T, et al. Selective ERK inhibitor ulixertinib inhibits proliferation and induces apoptosis in lymphoma cell lines[J]. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, 2016, 9(6): 10955-10962.
[2] Meloche S, Pouysségur J. The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1-to S-phase transition[J]. Oncogene, 2007, 26(22): 3227-3239.
[3] Germann U, Furey B, Roix J, et al. The selective ERK inhibitor BVD-523 is active in models of MAPK pathway-dependent cancers, including those with intrinsic and acquired drug resistance[J]. 2015.
[4] Infante J R, Janku F, Tolcher A W, et al. Dose escalation stage of a first-in-class phase I study of the novel oral ERK 1/2 kinase inhibitor BVD-523 (ulixertinib) in patients with advanced solid tumors[J]. 2015
.| Cas No. | 1956366-10-1 | SDF | |
| 别名 | BVD-523盐酸盐,BVD-523,VRT-752271 | ||
| 化学名 | 4-[5-chloro-2-[(1-methylethyl)amino]-4-pyridinyl]-N-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide, monohydrochloride | ||
| Canonical SMILES | CC(C)NC1=CC(C2=CNC(C(N[C@H](CO)C3=CC(Cl)=CC=C3)=O)=C2)=C(Cl)C=N1.Cl | ||
| 分子式 | C21H22Cl2N4O2 • HCl | 分子量 | 469.8 |
| 溶解度 | ≤1mg/ml in ethanol;30mg/ml in DMSO;30mg/ml in dimethyl formamide | 储存条件 | Store at -20°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 | 2.1286 mL | 10.6428 mL | 21.2857 mL |
| 5 mM | 0.4257 mL | 2.1286 mL | 4.2571 mL |
| 10 mM | 0.2129 mL | 1.0643 mL | 2.1286 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet