Ruxolitinib

別名：INCB018424

製品コード：S1378 純度：99.98%

ルクソリチニブ (Ruxolitinib (INCB018424)) は、最初に臨床試験が行われた強力で選択的なJAK1/2 阻害剤であり、IC50 はそれぞれ 3.3 nM/ 2.8 nM、JAK1/2 に対して JAK3 の 130 倍の選択性を示します。ルクソリチニブはマイトファジー (mitophagy) によって抗腫瘍作用を示します。また、オートファジー (autophagy) を誘導し、アポトーシス (apoptosis) を促進します。

CAS No. 941678-49-5

サイズ	価格(税別)	在庫状況
5mg	JPY 24000	国内在庫あり
25mg	JPY 48000	国内在庫あり
100mg	JPY 120000	国内在庫あり
1g	JPY 442000	国内在庫あり

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（556）

製品安全説明書

現在のバッチを見る：純度： 99.98%

99.98

Ruxolitinibと併用されることが多い化合物

Linifanib (ABT-869)

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

Hart S, et al. Blood Cancer J. 2011 Nov;1(11):e44.

Ibrutinib

Ruxolitinib and Ibrutinib combination effectively inhibits JAK-signaling and is well-tolerated in patients with chronic lymphocytic leukemia (CLL).

Spaner DE, et al. Cancer Med. 2019 Apr;8(4):1540-1550.

TP-3654

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

Dutta A, et al. Leukemia. 2022 Mar;36(3):746-759.

Sonidegib

Ruxolitinib and Sonidegib combination significantly reduce blood counts, mutant allele burden, and bone marrow fibrosis.

Kaplan JB, et al. EBioMedicine. 2016 Jan 13;3:17-25.

Hydroxyurea

Ruxolitinib and Hydroxyurea combination has significant advantages in spleen reduction and increasing overall survival (OS) and is a beneficial targeted treatment for myelofibrosis (MF).

Li Y, et al. Ann Hematol. 2020 Jun;99(6):1161-1176.

Ruxolitinib関連製品

関連ターゲット	JAK1 JAK2 JAK3 Tyk2	もっと見る
関連製品	Tofacitinib (CP-690550) Citrate Ruxolitinib Phosphate Tofacitinib AZD1480 Fedratinib (TG101348) WP1066 Baricitinib Momelotinib (CYT387) Filgotinib (GLPG0634) AT9283 S-Ruxolitinib (INCB018424) Gandotinib (LY2784544) TG101209 Cerdulatinib (PRT062070) hydrochloride Baricitinib phosphate Pacritinib NVP-BSK805 2HCl WHI-P154 FLLL32 Decernotinib (VX-509) CEP-33779 Upadacitinib AZ 960 Cerdulatinib (PRT062070) ZM 39923 HCl XL019 BMS-911543 Curcumol Solcitinib Oclacitinib maleate Pyridone 6 Abrocitinib (PF-04965842) Creatine Ritlecitinib (PF-06651600) Deucravacitinib (BMS-986165) Itacitinib (INCB39110) Peficitinib BD750 WHI-P97 JANEX-1 Brevilin A 1,2,3,4,5,6-Hexabromocyclohexane Brepocitinib (PF-06700841) FM-381 SAR-20347 Selective JAK3 inhibitor 1	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library FDA-approved Drug Library Natural Product Library Tyrosine Kinase Inhibitor Library JAK/STAT compound library	もっと見る

シグナル伝達経路

JAKシグナル伝達経路

JAK阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
A549/DDP	Function Assay	30 nM	48 h	Down-regulation of STAT3 phosphorylation	25213670
NCI-H2347	Function Assay	30 nM	48 h	Decrease in Bcl2 expression	25213670
NCI-H1299	Function Assay	30 nM	48 h	Down-regulation of STAT3 phosphorylation	25213670
A549/DDP	Apoptosis Assay	30 nM	48 h	Induction of apoptosis	25213670
NCI-H1299	Apoptosis Assay	30 nM	48 h	Induction of apoptosis	25213670
NCI-H2347	Apoptosis Assay	30 nM	48 h	Induction of apoptosis	25213670
Hep3B	Function Assay	1 μM	16 h	Impaires the capacity of IHCA-associated gp130 mutants to active STAT3 with IC50 of ~50 μM	24501689
HepG2	Function Assay	1 μM	16 h	Impaires the capacity of IHCA-associated gp130 mutants to signal to STAT3	24501689
Huh7	Function Assay	1 μM	16 h	Impaires the capacity of IHCA-associated gp130 mutants to signal to STAT3	24501689
BaF3	Kinase Assay	80 nM	6 h	Reduces the phosphorylation of STAT5 in JAK2V617F-mutated BAF3-EPOR cell	24237791
DLD-1	Kinase Assay	25 μM	48 h	Inhibition of JAK1 phosphorylation	24050550
RKO	Kinase Assay	25 μM	48 h	Inhibition of JAK1 phosphorylation	24050550
DLD-1	Kinase Assay	25 μM	48 h	Inhibition of JAK2 phosphorylation	24050550
RKO	Kinase Assay	25 μM	48 h	does not inhibit JAK1 phosphorylation	24050550
RKO	Growth Inhibition Assay	50 μM	48 h	IC50=14.76 μM	24050550
DLD-1	Growth Inhibition Assay	50 μM	48 h	IC50=15.51 μM	24050550
DLD-1	Apoptosis Assay	25 μM	48 h	Induces apoptosis by activating caspase 3	24050550
RKO	Apoptosis Assay	25 μM	48 h	Induces apoptosis by activating caspase 3	24050550
HuH7	Growth Inhibition Assay	50 μM	48 h	>82% reduction	23941832
SNU182	Growth Inhibition Assay	50 μM	48 h	>64% reduction	23941832
SNU423	Growth Inhibition Assay	50 μM	48 h	>81% reduction	23941832
HuH7	Function Assay	50 μM	24 h	Inhibition of STAT1 and STAT3 phosphorylation significantly	23941832
SNU182	Function Assay	50 μM	24 h	Inhibition of STAT1 and STAT3 phosphorylation significantly	23941832
SNU423	Function Assay	50 μM	24 h	Inhibition of STAT1 and STAT3 phosphorylation significantly	23941832
HT93A	Growth Inhibition Assay	320 nM	5 d	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
TF1	Kinase Assay		20 min	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	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
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
TF1 cells	JAK inhibition assay		20 min	EC50 = 0.012 μM	22698084
Sf21 cells	TYK2 inhibition assay		1 h	IC50 = 0.019 μM	22591402
TF1 cells	JAK inhibition assay		20 min	EC50 = 0.024 μM	22698084
Sf21 cells	JAK inhibition assay		1 h	IC50 = 0.428 μM	22591402
CD34+ cells	JAK inhibition assay		45 min	IC50 = 0.677 μM	24417533
NCI-H2347	Growth Inhibition Assay			IC50=0.17 μM	25213670
NCI-H1299	Growth Inhibition Assay			IC50=0.28 μM	25213670
A549/DDP	Growth Inhibition Assay			IC50=0.22 μM	25213670
A549	Growth Inhibition Assay			IC50=0.04 μM	25213670
NCI-H358	Growth Inhibition Assay			IC50=0.1 μM	25213670
NCI-H460	Growth Inhibition Assay			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
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
SET2 cells	JAK inhibition assay			IC50 = 0.00184 μM	23061660
CD34+ cells	JAK inhibition assay			IC50 = 0.008 μM	26927423
T cells	JAK inhibition assay			IC50 = 0.023 μM	23540648
T cells	JAK inhibition assay			IC50 = 0.023 μM	23540648
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
PBMC cells	STAT5 inhibition assay			IC50 = 0.448 μM	26927423
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

Targets

JAK2 ^[1] (Cell-free assay)	JAK1 ^[1] (Cell-free assay)
2.8 nM	3.3 nM

In Vitro
In vitro	INCB018424 potently and selectively inhibits JAK2V617F-mediated signaling and proliferation in Ba/F3 cells and HEL cells. INCB018424 markedly increases apoptosis in a dose dependent manner in Ba/F3 cells. INCB018424 (64 nM) results in a doubling of cells with depolarized mitochondria in Ba/F3 cells. INCB018424 inhibits proliferating of erythroid progenitors from normal donors and polycythemia vera patients with IC50 of 407 nM and 223 nM, respectively. INCB018424 demonstrates remarkable potency against erythroid colony formation with IC50 of 67nM. ^[1]
Kinase Assay	Binding assay
Kinase 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 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 INCB018424 concentration required for inhibition of 50% of the fluorescent signal.
細胞実験	細胞株	Ba/F3 and HEL cells
	濃度	3 μM
	反応時間	48 hours
	実験の流れ	Cells are seeded at 2 × 10³/well of white bottom 96-well plates, treated with INCB018424 from DMSO stocks (0.2% final DMSO concentration), and incubated for 48 hours at 37 ℃ with 5% CO₂. Viability is measured by cellular ATP determination using the Cell-Titer Glo luciferase reagent or viable cell counting. Values are transformed to percent inhibition relative to vehicle control, and IC50 curves are fitted according to nonlinear regression analysis of the data using PRISM GraphPad.
実験結果図	Methods	Biomarkers	結果図	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		29849942
	Growth inhibition assay	Cell viability Cell apoptosis Cell proliferation		29849942
	Immunofluorescence	α-tubulin		26356819

In Vivo
In Vivo	INCB018424 (180 mg/kg, orally, twice a day) results in survive rate of greater than 90% by day 22 in a JAK2V617F-driven mouse model. INCB018424 (180 mg/kg, orally, twice a day) markedly reduces splenomegaly and circulating levels of inflammatory cytokines, and preferentially eliminated neoplastic cells, resulting in significantly prolonged survival without myelosuppressive or immunosuppressive effects in a JAK2V617F-driven mouse model. ^[1] The primary end point is reached in 41.9% of patients in the Ruxolitinib group as compared with 0.7% in the placebo group in the double-blind trial of myelofibrosis. Ruxolitinib results in maintaining of reduction in spleen volume and improvement of 50% or more in the total symptom score. ^[2] A total of 28% of the patients in the Ruxolitinib (15 mg twice daily) group 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 Ruxolitinib 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. ^[3]
動物実験	動物モデル	JAK2V617F-driven mouse model
	投与量	180 mg/kg
	投与経路	Oral gavage

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT05762640	Not yet recruiting	Haemophagocytic Lymphohistiocytosis	Assistance Publique - Hôpitaux de Paris	March 2024	Phase 2
NCT05998408	Not yet recruiting	Severe Aplastic Anemia\|Single Lineage Cytopenias T-LGL\|Hypoplastic MDS	National Heart Lung and Blood Institute (NHLBI)\|National Institutes of Health Clinical Center (CC)	January 12 2024	Phase 1\|Phase 2
NCT05998395	Recruiting	Kohlmeier Degos Disease With Neurologic Involvement	National Heart Lung and Blood Institute (NHLBI)\|National Institutes of Health Clinical Center (CC)	September 28 2023	Phase 1\|Phase 2

参考
[1] Quintas-Cardama A, et al. Blood, 2010, 115(15), 3109-3117. [2] Verstovsek S, et al. N Engl J Med, 2012, 366(9), 799-807. [3] Harrison C, et al. N Engl J Med, 2012, 366(9), 787-798.

参考

化学情報

分子量	306.37	化学式	C₁₇H₁₈N₆
CAS No.	941678-49-5	SDF	Download Ruxolitinib SDFをダウンロードする
Smiles	C1CCC(C1)C(CC#N)N2C=C(C=N2)C3=C4C=CNC4=NC=N3
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 61 mg/mL ( (199.1 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 12 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

技術サポート

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

* 必須

よくある質問（FAQ）

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

回答
These two chemicals are the two different chiral forms of Ruxolitinib. S2902 S-Ruxolitinib is the S form and S1378 Ruxolitinib is the D form. One of the carbon atoms in this molecule 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.

質問2:
How about the half-life of the compound (Ruxolitinib)? How long is the duration of the inhibitory effect on JAK-STAT signaling?

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

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):