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JAK/STAT
JAK inhibitor
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Autophagy activator
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Mitophagy activator
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Apoptosis related activator
Ruxolitinib
僅限科研使用
Ruxolitinib
別名: INCB018424 中文名稱：魯索替尼
Ruxolitinib是第一個應(yīng)用于臨床的，有效的，選擇性JAK1/2抑制劑，在無細胞試驗中IC50為3.3 nM/2.8 nM。作用于JAK1， JAK2與作用于JAK3相比，選擇性高130多倍。Ruxolitinib 通過毒性線粒體自噬殺死腫瘤細胞。Ruxolitinib 可誘導(dǎo)自噬并增強細胞凋亡。
Ruxolitinib Chemical Structure
CAS: 941678-49-5
產(chǎn)品質(zhì)控
批次：
純度：
99.98%
99.98
常與Ruxolitinib一起在實驗中被使用的化合物
Ruxolitinib和Linifanib聯(lián)合對急性髓性白血病(AML)患者的FMS樣酪氨酸激酶3 (FLT3)抑制具有協(xié)同作用。
Ruxolitinib和Ibrutinib聯(lián)合使用可有效抑制JAK信號，并在慢性淋巴細胞白血病(CLL)患者中具有良好的耐受性。
Ruxolitinib和TP-3654聯(lián)合用藥對MPLW515L小鼠骨髓(BM)纖維化的抑制作用顯著增強。
Ruxolitinib和Sonidegib聯(lián)合使用可顯著降低血細胞計數(shù)、突變等位基因負擔(dān)和骨髓纖維化。
Ruxolitinib和Hydroxyurea在減脾和提高OS方面具有顯著優(yōu)勢，是一種有益的骨髓纖維化(MF)靶向治療方法。
Ruxolitinib相關(guān)產(chǎn)品
相關(guān)信號通路圖
細胞實驗數(shù)據(jù)示例
| 細胞系 | 實驗類型 | 給藥濃度 | 孵育時間 | 活性描述 | 文獻信息 |
|---|---|---|---|---|---|
| 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 | ||
| 點擊查看更多細胞系數(shù)據(jù) | |||||
生物活性
| 產(chǎn)品描述 | Ruxolitinib是第一個應(yīng)用于臨床的，有效的，選擇性JAK1/2抑制劑，在無細胞試驗中IC50為3.3 nM/2.8 nM。作用于JAK1， JAK2與作用于JAK3相比，選擇性高130多倍。Ruxolitinib 通過毒性線粒體自噬殺死腫瘤細胞。Ruxolitinib 可誘導(dǎo)自噬并增強細胞凋亡。 | ||||
|---|---|---|---|---|---|
| 靶點 |
|
| 體外研究(In Vitro) | ||||
| 體外研究活性 | 在Ba/F3細胞和HEL細胞中，INCB018424有效地和有選擇性地抑制JAK2V617F介導(dǎo)的信號傳導(dǎo)和細胞增殖。INCB018424以劑量依賴性的方式顯著地增加Ba/F3細胞的細胞凋亡。在Ba/F3細胞中，INCB018424(64 nM)致使線粒體去極化細胞增加一倍。INCB018424抑制來自正常捐助者和真性紅細胞增多癥患者的紅細胞前體細胞的增殖，IC50分別是407 nM 和223 nM。 INCB018424有效抑制紅細胞集落形成，IC50是67 nM。[1] | |||
|---|---|---|---|---|
| 激酶實驗 | 結(jié)合試驗 | |||
| 重組蛋白是使用Sf21細胞和桿狀病毒載體表達的，并通過親和層析純化。JAK激酶測定使用肽底物（-EQEDEPEGDYFEWLE）的均相時間分辨熒光測定法。酶反應(yīng)是用Ruxolitinib或?qū)φ?，JAK酶，500 nM肽，三磷酸腺苷（ATP; 1mM），和2％的二甲基亞砜（DMSO）反應(yīng)1小時。 50％抑制濃度（IC50）時需要抑制50％熒光信號的INCB018424濃度。 | ||||
| 細胞實驗 | 細胞系 | Ba/F3和HEL細胞 | ||
| 濃度 | 3 μM | |||
| 孵育時間 | 48小時 | |||
| 方法 | 2×103細胞接種于的96孔板的一個孔中，用溶于DMSO的INCB018424（0.2％DMSO終濃度）在37℃和5% CO2條件下溫育48小時。存活率是通過使用細胞滴度格洛熒光素酶試劑或活細胞計數(shù)器測定ATP水平。數(shù)值轉(zhuǎn)換為相比對照的抑制百分率， IC50曲線使用Prism的GraphPad數(shù)據(jù)的非線性回歸分析擬合。 | |||
| 實驗圖片 | 檢測方法 | 檢測指標 | 實驗圖片 | 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 | |
| 體內(nèi)研究(In Vivo) | ||
| 體內(nèi)研究活性 | INCB018424（180 mg/kg，口服，每日兩次）導(dǎo)致JAK2V617F驅(qū)動的小鼠模型的生存率在處理22天后大于90％。在JAK2V617F驅(qū)動的小鼠模型中，INCB018424（180 mg/kg，口服，每日兩次）顯著降低脾臟腫大和炎癥因子的循環(huán)水平，并優(yōu)先消滅腫瘤細胞，造成顯著延長的生存期，無骨髓抑制或免疫抑制作用。[1] 在骨髓纖維化的雙盲試驗中，Ruxolitinib組的主要終點達到41.9％，安慰劑組則為0.7％。 Ruxolitinib導(dǎo)致脾體積持續(xù)減少和總癥狀得分提高50％或更多。[2] 在Ruxolitinib（15 mg，每天兩次）組內(nèi)，共28％骨髓纖維化患者至48周時脾臟體積減少至少35％，而接受最好的治療組的比例為0%。Ruxolitinib致使脾臟長度減少了56％，而接受最好的治療組卻增加了4％。Ruxolitinib組患者的生活質(zhì)量得到提高和骨髓纖維化相關(guān)癥狀減少。[3] | |
|---|---|---|
| 動物實驗 | Animal Models | JAK2V617F驅(qū)動的小鼠模型 |
| Dosages | 180 mg/kg | |
| Administration | 口服 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| 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 |
化學(xué)信息&溶解度
| 分子量 | 306.37 | 分子式 | C17H18N6 |
| CAS號 | 941678-49-5 | SDF | Download Ruxolitinib SDF |
| Smiles | C1CCC(C1)C(CC#N)N2C=C(C=N2)C3=C4C=CNC4=NC=N3 | ||
| 儲存條件(自收到貨起) | |||
|
體外溶解度 |
DMSO : 144 mg/mL ( (470.01 mM) Ultrasonicated; ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO) Ethanol : 12 mg/mL (39.16 mM) Water : Insoluble |
摩爾濃度計算器 |
|
體內(nèi)溶解度 現(xiàn)配現(xiàn)用，請按從左到右的順序依次添加，澄清后再加入下一溶劑 |
動物體內(nèi)配方計算器 | ||||
實驗計算
動物體內(nèi)配方計算器（澄清溶液）
第一步：請輸入基本實驗信息（考慮到實驗過程中的損耗，建議多配一只動物的藥量）
mg/kg
g
μL
只
第二步：請輸入動物體內(nèi)配方組成（配方適用于不溶于水的藥物；不同批次藥物配方比例不同，請聯(lián)系Selleck為您提供正確的澄清溶液配方）
% DMSO
%
% Tween 80
% ddH2O
%DMSO
%
計算結(jié)果：
工作液濃度： mg/ml；
DMSO母液配制方法： mg 藥物溶于μL DMSO溶液（母液濃度mg/mL，注：如該濃度超過該批次藥物DMSO溶解度，請先聯(lián)系Selleck）；
體內(nèi)配方配制方法：取μL DMSO母液，加入μL PEG300，混勻澄清后加入μL Tween 80，混勻澄清后加入μL ddH2O，混勻澄清。
體內(nèi)配方配制方法：取μL DMSO母液，加入μL Corn oil，混勻澄清。
注意：1. 首先保證母液是澄清的；
2.一定要按照順序依次將溶劑加入，進行下一步操作之前必須保證上一步操作得到的是澄清的溶液，可采用渦旋、超聲或水浴加熱等物理方法助溶。
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常見問題及建議解決方法
問題 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.
問題 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.
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