Ulixertinib (BVD-523)

別名: VRT752271

目錄號：S7854 Purity: 99.99%

Ulixertinib (BVD-523, VRT752271)是有效的可逆ERK1/ERK2抑制劑，其抑制ERK2的IC50<0.3 nM 。Phase 1。

Ulixertinib (BVD-523) Chemical Structure

CAS: 869886-67-9

規(guī)格	價格	庫存
10mM (1mL in DMSO)	1449.63	現(xiàn)貨
5mg	1222.42	現(xiàn)貨
25mg	3643.55	現(xiàn)貨
100mg	8157.89	現(xiàn)貨
1g	12039.3	現(xiàn)貨
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產(chǎn)品質(zhì)控

批次：純度： 99.99%

99.99

常與Ulixertinib (BVD-523)一起在實驗中被使用的化合物

Encorafenib

在有BRAFV600E突變的CRC中，Ulixertinib、Encorafenib和Cetuximab聯(lián)合治療對腫瘤生長的抑制效果較好。

Knoerzer D, et al. Cancer Res (2023) 83 (7_Supplement): 2693.

SHP099

Ulixertinib和SHP099抑制SK-N-AS和CHP-212細胞中的下游MAPK信號傳導，并導致異種移植小鼠模型中的腫瘤生長延遲。

Valencia-Sama I, et al. Cancer Res. 2020 Aug 15;80(16):3413-3423.

Trametinib (GSK1120212)

Ulixertinib和Trametinib加上Trastuzumab deruxtecan非常有效，可在所有PDX模型中實現(xiàn)腫瘤完全消退。

Bulle AS, et al. Cancer Res (2022) 82 (12_Supplement): 5333.

Palbociclib

Ulixertinib和Palbociclib在MB1998患者來源的異種移植(PDX)模型中表現(xiàn)出顯著的腫瘤生長抑制作用。

Nassar KW, et al. Mol Cancer Ther. 2021 Oct;20(10):2049-2060.

Gemcitabine

Ulixertinib增強Gemcitabine在HPNE-KRAS G12D細胞中的促凋亡作用，有效抑制MIA Paca-2異種移植物的腫瘤生長。

Jiang H, et al. Mol Cancer Ther. 2018 Oct;17(10):2144-2155.

Ulixertinib (BVD-523)相關產(chǎn)品

相關靶點	ERK1 ERK2 ERK5 ERK1/2	點擊展開
相關產(chǎn)品	SCH772984 Ravoxertinib (GDC-0994) Temuterkib (LY3214996) FR 180204 XMD8-92 VX-11e AZD0364 (ATG-017) ERK5-IN-1 MK-8353 (SCH900353) DEL-22379 Astragaloside IV KO-947 Magnolin Senkyunolide I Pluripotin (SC1) DMU-212 CC-90003 BAY-885 AG-126	點擊展開
相關化合物庫	激酶抑制劑庫 MAPK抑制劑庫細胞周期化合物庫 TGF-beta/Smad信號通路庫抗阿爾茨海默病化合物庫	點擊展開

細胞實驗數(shù)據(jù)示例

細胞系	實驗類型	孵育時間	活性描述	文獻信息
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
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生物活性

產(chǎn)品描述

Ulixertinib (BVD-523, VRT752271)是有效的可逆ERK1/ERK2抑制劑，其抑制ERK2的IC50<0.3 nM 。Phase 1。

靶點

ERK1 ^[1]	ERK2 ^[1]
	<0.3 nM

體外研究(In Vitro)
體外研究活性	在一個包含b-RAFV600E突變體的A375黑色素瘤細胞中，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分別為4.1/0.14 μM。Ulixertinib也會抑制A375細胞增殖，IC50為180 nM。^[1]
激酶實驗	ERK2催化抑制的Rapidfire質(zhì)譜分析試驗
激酶實驗	MEK U911活化的ERK2蛋白在組織內(nèi)部表達并純化。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的試驗緩沖液中制備。1.2 nM ERK2蛋白質(zhì)在試驗緩沖液中制備，將10μL加入包含測試和對照品化合物的聚丙烯384孔板的每個孔中。化合物板預先加入范圍為100μM 到0.1 nM 的12個不同劑量，以計算化合物IC50s，與1%試驗化合物中總DMSO濃度。酶和化合物在室溫下預培養(yǎng)20分鐘后，10μL 底物溶液加入16μM Erktide (IPTTPITTTYFFFK)和120μM ATP (測量Km) 組成的試驗緩沖液中。反應在室溫下進行20分鐘，然后加入80μL 1% (v/v)甲酸淬滅反應。然后試驗板在RapidFire質(zhì)譜分析平臺上運行以測量底物(未磷酸化的Erktide)和產(chǎn)物(磷酸化的Erktide)。
細胞實驗	細胞系	A375 細胞
	濃度	~30 μM
	孵育時間	72小時
	方法	A375細胞在DMEM，10% (v/v)胎牛血清和1% (v/v) L-谷氨酰胺組成的細胞培養(yǎng)基中培養(yǎng)。采集后，將細胞分別加入黑色384孔Costar板，在40μL總體積的細胞培養(yǎng)基中使每孔含有200個細胞，然后在37℃，90%相對濕度和5% CO₂旋轉(zhuǎn)式培養(yǎng)基中培養(yǎng)過夜。使用Labcyte Echo 555聲控分配器將測試化合物和對照品直接給藥至細胞板內(nèi)部308孔。細胞在30 μM到0.03 nM范圍內(nèi)以12個不同濃度給藥，計算化合物IC50s，與0.3%試驗化合物中總DMSO濃度。然后細胞板在37℃下培養(yǎng)72小時。將細胞中加入20 μL 含12%甲醛的PBS/A (4%終濃度) 和1:2000稀釋的Hoechst 33342固定并著色，在室溫下培育30分鐘，然后用PBS/A洗滌。使用Cellomics ArrayScanTM VTI成像平臺在著色的細胞平板上計數(shù)細胞。在第0天，細胞板依然固定，著色，并讀取數(shù)據(jù)生成細胞計數(shù)基線，以測定化合物細胞毒性以及抗增殖作用。
實驗圖片	檢測方法	檢測指標	實驗圖片	PMID
	Western blot	p-ERK / ERK / RRM2		28797284
	Growth inhibition assay	Cell viability		30771617

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試驗信息 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT04488003	Terminated	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	Completed	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

參考文獻
[1] Ward RA, et al. J Med Chem. 2015, 58(11), 4790-4801.

參考文獻

[1] Ward RA, et al. J Med Chem. 2015, 58(11), 4790-4801.