Home JAK/STAT JAK inhibitor Ruxolitinib (INCB18424)

연구용

Ruxolitinib (INCB18424) JAK1/2 inhibitor

제품 번호S1378

Ruxolitinib (INCB18424) is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM in cell-free assays, >130-fold selectivity for JAK1/2 versus JAK3. This compound kills tumor cells through toxic mitophagy. It induces autophagy and enhances apoptosis.
Ruxolitinib (INCB18424) JAK inhibitor Chemical Structure

화학 구조

분자량: 306.37

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품질 관리 (Quality Control)

배치: 순도: 99.98%
99.98

함께 자주 사용되는 제품 Ruxolitinib (INCB18424)

Linifanib (ABT-869)

It and Linifanib (ABT-869) combination have a synergistic effect on FMS-like tyrosine kinase 3 (FLT3) inhibition in acute myeloid leukemia (AML) patients.

TP-3654

It and TP-3654 combination exhibit a significantly greater reduction of bone marrow (BM) fibrosis in MPLW515L mice.

SB431542

Explore avenues to prevent or treat age-related metabolic dysfunction using this compound.

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
SNU423 Function Assay 50 μM 24 h DMSO Inhibition of STAT1 and STAT3 phosphorylation significantly 23941832
SNU182 Function Assay 50 μM 24 h DMSO Inhibition of STAT1 and STAT3 phosphorylation significantly 23941832
HuH7 Function Assay 50 μM 24 h DMSO Inhibition of STAT1 and STAT3 phosphorylation significantly 23941832
SNU423 Growth Inhibition Assay 50 μM 48 h DMSO >81% reduction 23941832
SNU182 Growth Inhibition Assay 50 μM 48 h DMSO >64% reduction 23941832
HuH7 Growth Inhibition Assay 50 μM 48 h DMSO >82% reduction 23941832
RKO Apoptosis Assay 25 μM 48 h DMSO Induces apoptosis by activating caspase 3 24050550
DLD-1 Apoptosis Assay 25 μM 48 h DMSO Induces apoptosis by activating caspase 3 24050550
DLD-1 Growth Inhibition Assay 50 μM 48 h DMSO IC50=15.51 μM 24050550
RKO Growth Inhibition Assay 50 μM 48 h DMSO IC50=14.76 μM 24050550
RKO Kinase Assay 25 μM 48 h DMSO does not inhibit JAK1 phosphorylation 24050550
DLD-1 Kinase Assay 25 μM 48 h DMSO Inhibition of JAK2 phosphorylation 24050550
RKO Kinase Assay 25 μM 48 h DMSO Inhibition of JAK1 phosphorylation 24050550
DLD-1 Kinase Assay 25 μM 48 h DMSO Inhibition of JAK1 phosphorylation 24050550
BaF3 Kinase Assay 80 nM 6 h DMSO Reduces the phosphorylation of STAT5 in JAK2V617F-mutated BAF3-EPOR cell 24237791
Huh7 Function Assay 1 μM 16 h DMSO Impaires the capacity of IHCA-associated gp130 mutants to signal to STAT3 24501689
HepG2 Function Assay 1 μM 16 h DMSO Impaires the capacity of IHCA-associated gp130 mutants to signal to STAT3 24501689
Hep3B Function Assay 1 μM 16 h DMSO Impaires the capacity of IHCA-associated gp130 mutants to active STAT3 with IC50 of ~50 μM 24501689
NCI-H2347 Apoptosis Assay 30 nM 48 h DMSO Induction of apoptosis 25213670
NCI-H1299 Apoptosis Assay 30 nM 48 h DMSO Induction of apoptosis 25213670
A549/DDP Apoptosis Assay 30 nM 48 h DMSO Induction of apoptosis 25213670
NCI-H1299 Function Assay 30 nM 48 h DMSO Down-regulation of STAT3 phosphorylation 25213670
NCI-H2347 Function Assay 30 nM 48 h DMSO Decrease in Bcl2 expression 25213670
A549/DDP Function Assay 30 nM 48 h DMSO Down-regulation of STAT3 phosphorylation 25213670
NCI-H2347 Growth Inhibition Assay DMSO IC50=0.17 μM 25213670
NCI-H1299 Growth Inhibition Assay DMSO IC50=0.28 μM 25213670
A549/DDP Growth Inhibition Assay DMSO IC50=0.22 μM 25213670
A549 Growth Inhibition Assay DMSO IC50=0.04 μM 25213670
NCI-H358 Growth Inhibition Assay DMSO IC50=0.1 μM 25213670
NCI-H460 Growth Inhibition Assay DMSO IC50=0.13 μM 25213670
CMK Growth Inhibition Assay Inhibition of CMK carrying the WT JAK cell proliferation with IC50 of 0.075 μM 25352124
CMK Growth Inhibition Assay Inhibition of CMK carrying the JAK3A63D mutation cell proliferation with IC50 of 0.163 μM 25352124
CMK Growth Inhibition Assay Inhibition of CMK carrying the JAK3A572V mutation cell proliferation 25352124
HT93A Growth Inhibition Assay 320 nM 5 d DMSO Inhibition of GCS-F induced granulocytic differentiation 25805962
SET-2 Cytotoxic Assay 5 μM 48 h Cytotoxic index=18.7% 25931349
HEL Cytotoxic Assay 5 μM 48 h Cytotoxic index=12.2% 25931349
Human monocyte Kinase Assay Inhibition of JAK2/1 in human monocytes expressing CD14 assessed as inhibition of IFNgamma-stimulated STAT1 phosphorylation with IC50 of 0.031μM 23540648
Human monocyte Kinase Assay Inhibition of JAK2 in human monocytes expressing CD14 assessed as inhibition of GM-CSF-stimulated STAT5a phosphorylation with IC50 of 0.026μM 23540648
Human T cell Kinase Assay Inhibition of JAK3/1 in human T cells expressing CD3 assessed as inhibition of IL2-stimulated STAT5a phosphorylation with IC50 of 0.023μM 23540648
TF1 Kinase Assay 20 min DMSO Inhibition of JAK1 in human TF1 cells assessed as inhibition of IL6-induced STAT3 phosphorylation with IC50 of 0.024μM 22698084
TF1 Kinase Assay 20 min DMSO Inhibition of JAK2 in human TF1 cells assessed as inhibition of EPO-induced STAT5 phosphorylation with IC50 of 0.012μM 22698084
Sf9 cells JAK inhibition assay 1 h Ki = 0.0001 μM 23668484
Sf9 cells JAK inhibition assay 1 h Ki = 0.0002 μM 23668484
Sf9 cells JAK inhibition assay 1 h Ki = 0.0005 μM 23668484
SET2 cells JAK inhibition assay IC50 = 0.00184 μM 23061660
Sf21 cells JAK inhibition assay 1 h IC50 = 0.0028 μM 22591402
Sf21 cells JAK inhibition assay 60 min IC50 = 0.003 μM 27137359
Sf9 cells JAK inhibition assay 1 h Ki = 0.0032 μM 23668484
Sf21 cells JAK inhibition assay 1 h IC50 = 0.0033 μM 22591402
TF1 cells JAK inhibition assay 30 min IC50 = 0.00685 μM 23061660
CD34+ cells JAK inhibition assay IC50 = 0.008 μM 26927423
TF1 cells JAK inhibition assay 20 min EC50 = 0.012 μM 22698084
Sf21 cells TYK2 inhibition assay 1 h IC50 = 0.019 μM 22591402
T cells JAK inhibition assay IC50 = 0.023 μM 23540648
T cells JAK inhibition assay IC50 = 0.023 μM 23540648
TF1 cells JAK inhibition assay 20 min EC50 = 0.024 μM 22698084
T cells JAK inhibition assay IC50 = 0.031 μM 23540648
T cells JAK inhibition assay IC50 = 0.031 μM 23540648
PBMC cells JAK inhibition assay IC50 = 0.04 μM 26927423
Sf21 cells JAK inhibition assay 1 h IC50 = 0.428 μM 22591402
PBMC cells STAT5 inhibition assay IC50 = 0.448 μM 26927423
CD34+ cells JAK inhibition assay 45 min IC50 = 0.677 μM 24417533
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 306.37 화학식

C17H18N6

 보관 (수령일로부터) 3 years-20°C(in the dark) powder
CAS 번호 941678-49-5 SDF 다운로드 원액 보관

동의어 INCB018424 Smiles C1CCC(C1)C(CC#N)N2C=C(C=N2)C3=C4C=CNC4=NC=N3

용해도 (Solubility)

In vitro
배치:

DMSO : 300 mg/mL (979.2 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Ethanol : 12 mg/mL

Water : 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
JAK2
(Cell-free assay)
2.8 nM
JAK1
(Cell-free assay)
3.3 nM
시험관 내(In vitro)
Ruxolitinib (INCB18424) potently and selectively inhibits JAK2V617F-mediated signaling and proliferation in Ba/F3 cells and HEL cells. This compound markedly increases apoptosis in a dose dependent manner in Ba/F3 cells. It (64 nM) results in a doubling of cells with depolarized mitochondria in Ba/F3 cells. This chemical inhibits proliferating of erythroid progenitors from normal donors and polycythemia vera patients with IC50 of 407 nM and 223 nM, respectively. It demonstrates remarkable potency against erythroid colony formation with IC50 of 67nM.
키나아제 분석
Binding assay
Recombinant proteins are expressed using Sf21 cells and baculovirus vectors and purified with affinity chromatography. JAK kinase assays use a homogeneous time-resolved fluorescence assay with the peptide substrate (-EQEDEPEGDYFEWLE). Each enzyme reaction is carried out with Ruxolitinib (INCB18424) or control, JAK enzyme, 500 nM peptide, adenosine triphosphate (ATP; 1mM), and 2% dimethyl sulfoxide (DMSO) for 1 hour. The 50% inhibitory concentration (IC50) is calculated as the concentration of this compound required for inhibition of 50% of the fluorescent signal.
생체 내(In vivo)
INCB018424 (180 mg/kg, orally, twice a day) results in a survival rate of greater than 90% by day 22 in a JAK2V617F-driven mouse model. This compound (180 mg/kg, orally, twice a day) markedly reduces splenomegaly and circulating levels of inflammatory cytokines, and preferentially eliminates neoplastic cells, resulting in significantly prolonged survival without myelosuppressive or immunosuppressive effects in a JAK2V617F-driven mouse model. In the double-blind trial of myelofibrosis, the primary end point is reached in 41.9% of patients in the Ruxolitinib (INCB18424) group as compared with 0.7% in the placebo group. It results in maintaining reduction in spleen volume and improvement of 50% or more in the total symptom score. A total of 28% of the patients in the group receiving this compound (15 mg twice daily) has at least a 35% reduction in spleen volume at week 48 in patients with myelofibrosis, as compared with 0% in the group receiving the best available therapy. The mean palpable spleen length has decreased by 56% with it but has increased by 4% with the best available therapy at week 48. Patients in the ruxolitinib group has an improvement in overall quality-of-life measures and a reduction in symptoms associated with myelofibrosis.
참조

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot cleaved PARP / cleaved caspase3 p-JAK2 / p-AKT / p-MAPK / Bcl-xl / MCL-1 c-Myc / c-Jun / Cyclin B / Cyclin D / Bcl-2 / HIF-1α p-STAT3
S1378-WB2
29849942
Growth inhibition assay Cell viability Cell apoptosis Cell proliferation
S1378-viability1
29849942
Immunofluorescence α-tubulin
S1378-IF1
26356819

임상시험 정보 (Clinical Trial Information)

(데이터 출처 https://clinicaltrials.gov, 업데이트 날짜 2024-05-22)

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT06397313 Not yet recruiting
Myelofibrosis
Ryvu Therapeutics SA
 September 2024 Phase 2
NCT06388564 Not yet recruiting
Chronic Graft-versus-host-disease
Incyte Corporation
 July 8 2024 Phase 2
NCT06251102 Not yet recruiting
Polycythemia Vera
Gruppo Italiano Malattie EMatologiche dell''Adulto
 July 2024 --
NCT06343792 Not yet recruiting
Steroid Refractory GVHD
ReAlta Life Sciences Inc.
 May 2024 Phase 2

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
What is the difference between S2902 and S1378 which seem to have same structure formula according to the product information?

답변:
These two chemicals are the two different chiral forms of this compound. S2902 S-Ruxolitinib is the S form and S1378 Ruxolitinib is the D form. One of the carbon atoms in it is asymmetric, making the two molecules mirror images of each other. The biological activities of these two molecules can be very different because of the confirmation differences.

질문 2:
How about the half-life of this compound? How long is the duration of its inhibitory effect on JAK-STAT signaling?

답변:
According to previous study, the half-life of this compound in body is about 2~3 hours. Generally, it is longer in vitro culture medium than in vivo. It was also used for 24 hours in paper. http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=24711661.