Ulixertinib (BVD-523)
别名: VRT752271
Ulixertinib (BVD-523, VRT752271)是有效的可逆ERK1/ERK2抑制剂，其抑制ERK2的IC50<0.3 nM 。Phase 1。
Ulixertinib (BVD-523) Chemical Structure
CAS: 869886-67-9
客户使用Selleck的Ulixertinib (BVD-523)发表文献56篇
产品质控
常与Ulixertinib (BVD-523)一起在实验中被使用的化合物
Knoerzer D, et al. Cancer Res (2023) 83 (7_Supplement): 2693.
Valencia-Sama I, et al. Cancer Res. 2020 Aug 15;80(16):3413-3423.
Bulle AS, et al. Cancer Res (2022) 82 (12_Supplement): 5333.
Nassar KW, et al. Mol Cancer Ther. 2021 Oct;20(10):2049-2060.
Ulixertinib (BVD-523)相关产品
相关信号通路图
ERK抑制剂选择性比较
细胞实验数据示例
| 细胞系 | 实验类型 | 给药浓度 | 孵育时间 | 活性描述 | 文献信息 |
|---|---|---|---|---|---|
| A375 | Function assay | 2 hrs | Inhibition of ERK1/2 in human A375 cells harboring B-RAF V600E mutant assessed as decrease in phospho-RSK level after 2 hrs by Cellomics ArrayScanTM VTI imaging analysis, IC50 = 0.14 μM. | 25977981 | |
| A375 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human A375 cells harboring B-RAF V600E mutant after 72 hrs by Cellomics ArrayScanTM VTI imaging analysis, IC50 = 0.18 μM. | 25977981 | |
| SKCO1 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human SKCO1 cells harboring KRAS G12V mutant after 72 hrs by CellTiter-Glo assay, IC50 = 0.356 μM. | 28038940 | |
| BA/F3 | Antiproliferative assay | 72 hrs | Antiproliferative activity against mouse BA/F3 cells harboring KRAS G12D mutant after 72 hrs by CellTiter-Glo assay, IC50 = 0.468 μM. | 28038940 | |
| SW620 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human SW620 cells harboring KRAS G12V mutant after 72 hrs by CellTiter-Glo assay, IC50 = 0.499 μM. | 28038940 | |
| AsPC1 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human AsPC1 cells harboring KRAS G12D mutant after 72 hrs by CellTiter-Glo assay, IC50 = 0.849 μM. | 28038940 | |
| NCI-H23 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human NCI-H23 cells harboring KRAS G12C mutant after 72 hrs by CellTiter-Glo assay, IC50 = 1 μM. | 28038940 | |
| SW156 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human SW156 cells harboring wild type KRAS after 72 hrs by CellTiter-Glo assay, IC50 = 1.24 μM. | 28038940 | |
| BA/F3 | Antiproliferative assay | 72 hrs | Antiproliferative activity against mouse BA/F3 cells after 72 hrs by CellTiter-Glo assay, IC50 = 2.231 μM. | 28038940 | |
| A375 | Function assay | 2 hrs | Inhibition of ERK2 in human A375 cells harboring B-RAF V600E mutant assessed as decrease in phospho-ERK2 level after 2 hrs by Cellomics ArrayScanTM VTI imaging analysis, IC50 = 4.1 μM. | 25977981 | |
| BA/F3 | Antiproliferative assay | 72 hrs | Antiproliferative activity against mouse BA/F3 cells harboring KRAS G12D mutant after 72 hrs in presence of IL-3 by CellTiter-Glo assay, IC50 = 8.608 μM. | 28038940 | |
| A375 | Function assay | Inhibition of ERK2 in human A375 cells harboring BRAF V600E mutant assessed as decrease in phosphorylated RSK levels, IC50 = 0.031 μM. | 28376306 | ||
| A375 | Function assay | Inhibition of ERK2 in human A375 cells harboring BRAF V600E mutant assessed as decrease in phosphorylated ERK2 levels, IC50 = 4.1 μM. | 28376306 | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | Ulixertinib (BVD-523, VRT752271)是有效的可逆ERK1/ERK2抑制剂，其抑制ERK2的IC50<0.3 nM 。Phase 1。 | ||||
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| 靶点 |
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| 体外研究(In Vitro) | ||||
| 体外研究活性 | 在一个包含b-RAFV600E突变体的A375黑色素瘤细胞中，Ulixertinib降低磷酸化的ERK2 (pERK)水平和下游激酶RSK (pRSK)的磷酸化水平，IC50分别为4.1/0.14 μM。Ulixertinib也会抑制A375细胞增殖，IC50为180 nM。[1] | |||
|---|---|---|---|---|
| 激酶实验 | ERK2催化抑制的Rapidfire质谱分析试验 | |||
| MEK U911活化的ERK2蛋白在组织内部表达并纯化。酶和底物溶液在包含50 mM Tris (pH 7.5)，10 mM MgCl2，0.1 mM EGTA，10 mM DTT 和 0.01% (v/v) CHAPS的试验缓冲液中制备。1.2 nM ERK2蛋白质在试验缓冲液中制备，将10μL加入包含测试和对照品化合物的聚丙烯384孔板的每个孔中。化合物板预先加入范围为100μM 到0.1 nM 的12个不同剂量，以计算化合物IC50s，与1%试验化合物中总DMSO浓度。酶和化合物在室温下预培养20分钟后，10μL 底物溶液加入16μM Erktide (IPTTPITTTYFFFK)和120μM ATP (测量Km) 组成的试验缓冲液中。反应在室温下进行20分钟，然后加入80μL 1% (v/v)甲酸淬灭反应。然后试验板在RapidFire质谱分析平台上运行以测量底物(未磷酸化的Erktide)和产物(磷酸化的Erktide)。 | ||||
| 细胞实验 | 细胞系 | A375 细胞 | ||
| 浓度 | ~30 μM | |||
| 孵育时间 | 72小时 | |||
| 方法 | A375细胞在DMEM，10% (v/v)胎牛血清和1% (v/v) L-谷氨酰胺组成的细胞培养基中培养。采集后，将细胞分别加入黑色384孔Costar板，在40μL总体积的细胞培养基中使每孔含有200个细胞，然后在37℃，90%相对湿度和5% CO2旋转式培养基中培养过夜。使用Labcyte Echo 555声控分配器将测试化合物和对照品直接给药至细胞板内部308孔。细胞在30 μM到0.03 nM范围内以12个不同浓度给药，计算化合物IC50s，与0.3%试验化合物中总DMSO浓度。然后细胞板在37℃下培养72小时。将细胞中加入20 μL 含12%甲醛的PBS/A (4%终浓度) 和1:2000稀释的Hoechst 33342固定并着色，在室温下培育30分钟，然后用PBS/A洗涤。使用Cellomics ArrayScanTM VTI成像平台在着色的细胞平板上计数细胞。在第0天，细胞板依然固定，着色，并读取数据生成细胞计数基线，以测定化合物细胞毒性以及抗增殖作用。 | |||
| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | p-ERK / ERK / RRM2 |
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28797284 | |
| Growth inhibition assay | Cell viability |
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30771617 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT04488003 | Active not recruiting | Advanced Solid Tumor|BRAF Gene Mutation|BRAF Gene Alteration|MEK Mutation|MEK Alteration|MAP2K1 Gene Mutation|MAP2K1 Gene Alteration|MAP2K2 Gene Mutation|MAP2K2 Gene Alteration |
BioMed Valley Discoveries Inc |
November 3 2020 | Phase 2 |
| NCT04145297 | Active not recruiting | Gastrointestinal Neoplasms |
University of Utah|BioMed Valley Discoveries Inc |
March 17 2020 | Phase 1 |
| NCT03698994 | Active not recruiting | Advanced Malignant Solid Neoplasm|Recurrent Ependymal Tumor|Recurrent Ewing Sarcoma|Recurrent Glioma|Recurrent Hepatoblastoma|Recurrent Histiocytic and Dendritic Cell Neoplasm|Recurrent Langerhans Cell Histiocytosis|Recurrent Malignant Germ Cell Tumor|Recurrent Malignant Solid Neoplasm|Recurrent Medulloblastoma|Recurrent Neuroblastoma|Recurrent Non-Hodgkin Lymphoma|Recurrent Osteosarcoma|Recurrent Peripheral Primitive Neuroectodermal Tumor|Recurrent Primary Malignant Central Nervous System Neoplasm|Recurrent Rhabdoid Tumor|Recurrent Rhabdomyosarcoma|Recurrent Soft Tissue Sarcoma|Refractory Ependymoma|Refractory Ewing Sarcoma|Refractory Glioma|Refractory Hepatoblastoma|Refractory Histiocytic and Dendritic Cell Neoplasm|Refractory Langerhans Cell Histiocytosis|Refractory Malignant Germ Cell Tumor|Refractory Malignant Solid Neoplasm|Refractory Medulloblastoma|Refractory Neuroblastoma|Refractory Non-Hodgkin Lymphoma|Refractory Osteosarcoma|Refractory Peripheral Primitive Neuroectodermal Tumor|Refractory Primary Malignant Central Nervous System Neoplasm|Refractory Rhabdoid Tumor|Refractory Rhabdomyosarcoma|Refractory Soft Tissue Sarcoma|Wilms Tumor |
National Cancer Institute (NCI) |
November 14 2018 | Phase 2 |
| NCT03417739 | Active not recruiting | Uveal Melanoma |
Dana-Farber Cancer Institute|BioMed Valley Discoveries Inc |
March 26 2018 | Phase 2 |
| NCT02994732 | Completed | Healthy |
BioMed Valley Discoveries Inc |
January 2017 | Phase 1 |
化学信息&溶解度
| 分子量 | 433.33 | 分子式 | C21H22Cl2N4O2 |
| CAS号 | 869886-67-9 | SDF | Download Ulixertinib (BVD-523) SDF |
| Smiles | CC(C)NC1=NC=C(C(=C1)C2=CNC(=C2)C(=O)NC(CO)C3=CC(=CC=C3)Cl)Cl | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 86 mg/mL ( (198.46 mM)； DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Ethanol : 86 mg/mL Water : Insoluble |
摩尔浓度计算器 |
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体内溶解度 现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂 |
动物体内配方计算器 | ||||
实验计算
动物体内配方计算器（澄清溶液）
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）
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Selleck为您提供正确的澄清溶液配方）
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，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；
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 ddH2O，混匀澄清。
体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。
注意：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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