SCH772984 HCl

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SCH772984 HCl

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:

942183-80-4

包装与价格：

包装	价格(元)
10mM (in 1mL DMSO)	电议
5mg	电议
10mg	电议
25mg	电议
50mg	电议

产品介绍

化学性质

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	624.17
Cas No.	942183-80-4 (free base)
Formula	C₃₃H₃₄ClN₉O₂
Solubility	≥23.5 mg/mL in H2O with gentle warming; insoluble in EtOH; ≥16.27 mg/mL in DMSO
Canonical SMILES	O=C(N1CCN(C2=CC=C(C3=NC=CC=N3)C=C2)CC1)CN4CC[C@@](/C(O)=N/C5=CC(C(C6=CC=NC=C6)=NN7)=C7C=C5)([H])C4.Cl
运输条件	蓝冰运输或根据您的需求运输。
一般建议	为了使其更好的溶解，请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。

资料参考

SCH772984 HCl is a specific inhibitor of extracellular signal-regulated kinase 1/2 (ERK1/2), with IC50 values of 4 nM and 1 nM, respectively [1].

ERK1/2 is a mitogen-activated protein kinase (MAPK) which is involved in the development of various cancers, especially the ones withBRAF orRAS mutations. Phospho-ERK reactivation in cancer cells is associated with resistance to BRAF and MEK inhibitors [1].

InBRAF^V600E-mutant human melanoma cell line LOXIMV1 (LOX), SCH772984 at 0 ~ 300 nM inhibited phosphorylation of the ERK substrate p90 ribosomal S6 kinase in a dose-dependent manner. SCH772984 also reduced phosphorylation of residues in the activation loop of ERK itself. In addition, for approximately 88% and 49% ofBRAF-mutant orRAS-mutant tumor lines, SCH772984 exhibited antiproliferative activity with EC50 values < 500 nM. SCH772984 effectively inhibited MAPK signaling and cell proliferation even in tumor cells resistant to concurrent treatment with BRAF and MAP-ERK kinase (MEK) inhibitors [1].

In female nude mice bearing human LOXBRAF^V600E tumors, SCH772984 (12.5, 25, 50 mg/kg, i.p., b.i.d., for 14 days) induced tumor regressions in a dose-dependent manner, and 98% tumor regression was achieved at the largest dose [1].

Reference:

[1]. Morris E J, Jha S, Restaino C R, et al. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discovery, 2013, 3(7): 742-750.

试验操作

Cell experiment:[1]
Cell lines	BRAF^V600E-mutant human melanoma cell line LOXIMV1 (LOX)
Reaction Conditions	0 ~ 300 nM SCH772984 for 24 h incubation
Applications	SCH772984 inhibited phosphorylation of the ERK substrate p90 ribosomal S6 kinase in a dose-dependent manner. SCH772984 also reduced phosphorylation of residues in the activation loop of ERK itself, a modification catalyzed by the ERK-activating kinases, MEK 1 and MEK 2.
Animal experiment:[1]
Animal models	Female nude mice bearing human LOXBRAF^V600Etumors
Dosage form	12.5, 25, 50 mg/kg Twice daily (b.i.d.) by intraperitoneal route (i.p.) for 14 days
Applications	In female nude mice bearing human LOXBRAF^V600Etumors, SCH772984 (12.5, 25, 50 mg/kg, i.p., b.i.d., for 14 days) induced tumor regressions in a dose-dependent manner, and 98% tumor regression was achieved at the largest dose.
Note	The technical data provided above is for reference only.
	References: 1. Morris E J, Jha S, Restaino C R, et al. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discovery, 2013, 3(7): 742-750.