Home MAPK JNK inhibitor SP600125

연구용

SP600125 JNK inhibitor

제품 번호: S1460

SP600125 (Nsc75890) is a broad-spectrum JNK inhibitor for JNK1, JNK2 and JNK3 with IC50 of 40 nM, 40 nM and 90 nM in cell-free assays, respectively; 10-fold greater selectivity against MKK4, 25-fold greater selectivity against MKK3, MKK6, PKB, and PKCα, and 100-fold selectivity against ERK2, p38, Chk1, EGFR etc. This compound is also a broad‐spectrum inhibitor of serine/threonine kinases including Aurora kinase A，FLT3 and TRKA with of IC50 of 60 nM, 90 nM and 70 nM. It inhibits autophagy and activates apoptosis.
SP600125 JNK inhibitor Chemical Structure

화학 구조

분자량: 220.23

바로가기

품질 관리 (Quality Control)

배치: 순도: 99.94%
99.94

함께 자주 사용되는 제품 SP600125

SB203580 (Adezmapimod)

It inhibits autophagy and activates apoptosis whereas, Adezmapimod induces mitophagy and autophagy.

PD 98059

It and PD98059 are two kinases that possess pro-survival activities in TQ-induced cell death.

SCH772984

It and SCH772984 significantly increase apoptosis of both PMN-MDSCs and M-MDSCs in vitro.

LY294002

It and LY294002 suppress cell growth of SNU-216 and NCI-N87 cells.

Bentamapimod (AS602801)

It and Bentamapimod are pan-JNK inhibitors that cause a robust reduction in cell viability in a panel of GBM stem cells (GSCs) cultures.

세포 배양, 처리 및 작업 농도
(Cell Culture, Treatment & Working Concentration)

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
Hep3B Function Assay 10 μM 1 h Blocks autophagy and upregulation of Beclin 1 expression induced by ceramide 19060920
BV-2 Function Assay 2 μM 1 h Inhibits the increase of sBAFF release in Gmix-treated BV-2 cells 19406831
RAW264.7 Function Assay 10 μM 12 h Antiinflammatory activity assessed as inhibition of LPS-induced NO production with IC50 of 17μM 19497418
PC3 Function Assay 20 μM 1 h Decreases the MMP2 and MMP9 expression 19633975
Plasmodium falciparum HB3 Antibacterial Assay 72 h DMSO Antiplasmodial activity with IC50 of 7.94328 μM 19734910
Plasmodium falciparum W2 Antibacterial Assay 72 h DMSO Antiplasmodial activity with IC50 of 7.94328 μM 19734910
Plasmodium falciparum 7G8 Antibacterial Assay 72 h DMSO Antiplasmodial activity with IC50 of 10 μM 19734910
Plasmodium falciparum 3D7 Antibacterial Assay 72 h DMSO Antiplasmodial activity with IC50 of 12.5893 μM 19734910
Plasmodium falciparum GB4 Antibacterial Assay 72 h DMSO Antiplasmodial activity with IC50 of 12.5893μM 19734910
HaCaT Function Assay 20 μM 4 h DMSO Blocks the TNF-α-induced CYP4F11 transcription 19812349
HaCaT Function Assay 20 μM 24 h DMSO Blocks the phosphorylation of c-Jun protein 19812349
A549 Function Assay 20 μM 1 h Inhibition of TPA-induced MMP-2 and u-PA expression 20492175
PC12 Function Assay 10 μM 5 h DMSO Activation of Nrf2/ARE assessed as HO-1 protein induction pretreated with PD98059 21345685
PC12 Function Assay 10 μM 5 h DMSO Activation of Nrf2/ARE assessed as HO-1 protein induction pretreated with U0126 21345685
PC12 Function Assay 10 μM 5 h DMSO Activation of Nrf2/ARE assessed as HO-1 protein induction pretreated with SP600125 21345685
PC12 Function Assay 10 μM 5 h DMSO Activation of Nrf2/ARE assessed as HO-1 protein induction pretreated with SB203580 21345685
B16-F10 Function Assay 1 h Inhibition of TNF-alpha-induced c-JUN phosphorylation 21815634
LoVo Function Assay 1 μM 1 h Inhibition of PGE2-induced expression of uPA and MMP-9 significantly 21859479
LoVo Function Assay 1 μM 1 h BlocksPGE2-induced cell migration significantly 21859479
THP-1 Function Assay 90 nM 30 min Inhibition of tissue factor expression 22940059
PC3 Function Assay 25 μM 24 h Inhibition of AP-1 and p21 luciferase activity induced by S179D PRL 23162652
SH-SY5Y Function Assay 10 μM 1 h DMSO Neuroprotective activity assessed as reduction of anisomycin-induced cell death 23498914
SH-SY5Y Kinase Assay 10 μM 1 h DMSO Inhibition of JNK3 assessed as blockade of anisomycin-induced c-jun phosphorylation at ser73 23498914
RAW264.7 Function Assay 10 μM 24 h Antiinflammatory activity assessed as inhibition of IL-1beta release 23791078
RAW264.7 Function Assay 10 μM 24 h Antiinflammatory activity assessed as inhibition of LPS-induced iNOS expression 23791078
RAW264.7 Function Assay 10 μM 2 h Antiinflammatory activity assessed as inhibition of LPS-induced NO production 23791078
A549 Growth Inhibition Assay 20 μM 72 h DMSO Rapid and potent inhibition of cell proliferation 23912840
RAW264.7 Antiinflammatory assay Antiinflammatory activity in mouse RAW264.7 cells assessed as inhibition of LPS-induced NO production relative to control, IC50 = 17 μM. 22831798
BMMC Function assay 1 to 20 uM 7 days Inhibition of RANKL/M-CSF-stimulated osteoclastogenesis in ICR mouse BMMC assessed as reduction in TRAP positive multinucleated cells at 1 to 20 uM incubated for 7 days by light microscopy 25397676
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
클릭하여 더 많은 세포주 실험 데이터 보기

화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 220.23 화학식

C14H8N2O

 보관 (수령일로부터)
CAS 번호 129-56-6 SDF 다운로드 원액 보관

동의어 Nsc75890 Smiles C1=CC=C2C(=C1)C3=NNC4=CC=CC(=C43)C2=O

용해도 (Solubility)

In vitro
배치:

DMSO : 60 mg/mL (272.44 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

몰농도 계산기

질량 농도 부피 분자량
희석 계산기 분자량 계산기

In vivo
배치:

생체 내 제형 계산기 (투명한 용액)

1단계: 아래 정보 입력 (권장: 실험 중 손실을 고려하여 추가 동물 포함)

mg/kg g μL

2단계: 생체 내 제형 입력 (이것은 계산기일 뿐 제형이 아닙니다. 용해도 섹션에 생체 내 제형이 없는 경우 먼저 당사에 문의하십시오.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

계산 결과:

작업 농도: mg/ml;

DMSO 원액 준비 방법: mg 약물 사전 용해 μL DMSO ( 원액 농도 mg/mL, 농도가 해당 약물 배치의 DMSO 용해도를 초과하는 경우 먼저 당사에 문의하십시오. )

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가μL PEG300, 혼합하고 투명하게 한 다음 추가μL Tween 80, 혼합하고 투명하게 한 다음 추가 μL ddH2O, 혼합하고 투명하게 합니다.

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가 μL 옥수수 기름, 혼합하고 투명하게 합니다.

참고: 1. 다음 용매를 추가하기 전에 액체가 투명한지 확인하십시오.
2. 용매를 순서대로 추가해야 합니다. 다음 용매를 추가하기 전에 이전 추가에서 얻은 용액이 투명한 용액인지 확인해야 합니다. 와동, 초음파 또는 뜨거운 물 중탕과 같은 물리적 방법을 사용하여 용해를 도울 수 있습니다.

작용 메커니즘 (Mechanism of Action)

Targets/IC50/Ki
serine/threonine kinase
JNK1
(Cell-free assay)
40 nM
JNK2
(Cell-free assay)
40 nM
Aurora A
(Cell-free assay)
60 nM
TrkA
(Cell-free assay)
70 nM
JNK3
(Cell-free assay)
90 nM
FLT3
(Cell-free assay)
90 nM
MKK4
(Cell-free assay)
0.4 μM
MKK6
(Cell-free assay)
1.0 μM
PKB
(Cell-free assay)
1.0 μM
MKK3
(Cell-free assay)
1.5 μM
PKCα
(Cell-free assay)
1.5 μM
시험관 내(In vitro)

SP600125 is originally characterized as a selective ATP-competitive inhibitor of c-Jun N-terminal kinase JNK. In Jurkat T cells, this compound inhibits the phosphorylation of c-Jun with IC50 of 5 μM to 10 μM. In CD4+ cells, such as Th0 cells isolated from either human cord or peripheral blood, it blocks cell activation and differentiation and inhibits the expression of inflammatory genes COX-2, IL-2, IL-10, IFN-γ, and TNF-α, with IC50 of 5 μM to 12 μM. However, later studies reveal that this chemical also suppresses aryl hydrocarbon receptor (AhR) , Mps1 , and a panel of other serine/threonine kinases, including Aurora kinase A, FLT3, MELK, and TRKA . In a mouse beta cells MIN6, this compound (20 μM) induces the phosphorylation of p38 MAPK and its downstream CREB-dependent promoter activation. In HCT116 cells, it (20 μM) blocks the G2 phase to mitosis transition and induces endoreplication. This ability of this inhibitor is independent of JNK inhibition, but due to its inhibition of CDK1-cyclin B activation upstream of Aurora A and Polo-like kinase 1.

키나아제 분석
In Vitro Kinase Assays
The potency of SP600125 towards kinases, including MPS1, JNK, and Aurora kinase A, is determined based on the specific measurement of radioactive phosphotransfer to the substrate. For each enzyme, the absolute Km values for ATP and the specific substrate are initially determined and each assay is then run at optimized [ATP] (2·αKm) and [substrate] (5·Km) concentrations. MPS1 activity is measured using 5 nM of MPS1 recombinant protein in 50 mM HEPES pH 7.5, 2.5 mM MgCl2, 1 mM MnCl2, 1 mM DTT, 3 μM NaVO3, 2 mM β-glycerophosphate, 0.2 mg/mL BSA, 200 μM P38-βtide substrate-peptide (KRQADEEMTGYVATRWYRAE), and 8 μM ATP with 1.5 nM 33P-γ-ATP. Ten serial 1:3 dilutions (from 30 μM to 1.5 nM) of this compound are tested and IC50 determined.
생체 내(In vivo)

In mice, SP600600125 (15 mg/kg or 30 mg/kg) significantly inhibits lipopolysaccharide (LPS)-induced TNF-α expression and anti-CD3-induced apoptosis of CD4+ CD8+ thymocytes.

참조
  • [4] https://pubmed.ncbi.nlm.nih.gov/21159646/
  • [5] https://pubmed.ncbi.nlm.nih.gov/12878189/
  • [6] https://pubmed.ncbi.nlm.nih.gov/20062077/

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot p-JNK p-IGF1R / IGF1R / p-Akt / Akt / p-ERK / ERK p-Src / Src p-c-Jun / c-Jun / pJNK / JNK Survivin / Bcl-2 / PARP p-FADD / FADD / p-c-Jun / c-Jun
S1460-WB1
25226534
Immunofluorescence AIF / Endo G E-cadherin / β-catenin α-catenin / Actin
S1460-IF1
21738692
Growth inhibition assay Cell viability (U-87 MG) Cell viability (A549)
S1460-viability
27176481

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
how to reconstitute the inhibitor for in vivo studies?

답변:
It can be dissolved in 5% DMSO/corn oil at 5 mg/ml as a clear solution for injection. For oral administration, this compound dissolved in vehicle 30% PEG400/0.5% Tween80/5%Propylene glycol, at 30mg/ml is a suspension and can be used.