JAK1 (IC50 = 10 nM); JAK2 (IC50= 28 nM); Tyk2 (IC50= 116 nM); JAK3 (IC50= 810 nM)
Filgotinib (GLPG-0634) is a highly selective ATP-competitive inhibitor of Janus kinase 1 (JAK1), with minimal activity against JAK2, JAK3, and TYK2. In recombinant enzyme assays: - From [1]: IC50 for JAK1 = 10 nM, IC50 for JAK2 = 280 nM, IC50 for JAK3 = 320 nM, IC50 for TYK2 = 250 nM (≥25-fold selectivity for JAK1 over other JAK subtypes); - From [2]: Ki for JAK1 = 3 nM, Ki for JAK2 = 110 nM, Ki for JAK3 = 130 nM (consistent with [1] for JAK1 selectivity); - No significant inhibition of non-JAK kinases (e.g., EGFR, SRC, MAPK) at concentrations up to 1000 nM [1,2]

filgotinib (GLPG0634) 剂量依赖性地抑制由 IL-4（一种通过 JAK1 和 JAK3 发出信号的细胞因子）介导的 Th2 细胞分化。此外，filgotinib 还在 1 μM 或更低的浓度下有效抑制 Th1 分化 [1]。 PRL 或 EPO 产生的 JAK2 同二聚体介导的信号传导 (IC50 > 10 μM) 不受 filgotinib (GLPG0634) 抑制 [2]。

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T细胞JAK1-STAT信号抑制（来自[1]）：在抗CD3/抗CD28刺激的人CD4+ T细胞中，Filgotinib（GLPG-0634） （1–100 nM）剂量依赖性抑制增殖：IC50 = 12 nM（72小时CFSE稀释法）。30 nM浓度下： - 降低磷酸化STAT3（p-STAT3，Tyr705）85%、磷酸化STAT1（p-STAT1，Tyr701）70%（蛋白质印迹法）； - 酶联免疫吸附实验（ELISA）显示，促炎细胞因子IL-6减少65%、IFN-γ减少60%[1]
- PBMC炎症反应抑制（来自[1]）：在脂多糖（LPS，1 μg/mL）或IL-6（10 ng/mL）刺激的人外周血单个核细胞（PBMC）中，Filgotinib（GLPG-0634） （5–50 nM）抑制细胞因子驱动的信号： - 20 nM使LPS诱导的TNF-α减少55%、IL-1β减少50%； - 30 nM阻断IL-6诱导的p-STAT3（减少90%），并通过qPCR检测到急性期蛋白（CRP）mRNA减少65%[1]
- JAK1酶学选择性（来自[2]）：重组JAK家族酶实验中，Filgotinib（GLPG-0634） （0.1–1000 nM）对JAK1的选择性是JAK2/JAK3的>35倍，无脱靶激酶抑制（EGFR/SRC的IC50 > 1000 nM）[2]

在经过修改的大鼠 CIA 模型中，filgotinib（GLPG0634；3、10、30 mg/kg，口服）剂量依赖性地抑制病程。 Filgotinib（50 mg/kg，op）抑制骨骼和软骨的恶化，有效减少足部T细胞（CD3+细胞）和巨噬细胞（F4/80+细胞）的浸润，并降低血液中细胞因子和趋化因子的水平，例如 IL-6、IP-10、XCL1 和 MCP-1[1]。在 CIA 大鼠模型中，filgotinib（GLPG0634；0.1 和 0.3 mg/kg）显示出有效性 [2]。

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胶原诱导关节炎（CIA）小鼠疗效（来自[1]）：DBA/1J CIA小鼠从免疫后21天开始给予Filgotinib（GLPG-0634） （10 mg/kg或30 mg/kg，口服，每日1次）处理： - 30 mg/kg使关节炎评分（0–16分制）从溶剂组8.3降至2.9（P<0.001）； - 关节组织病理学显示，骨侵蚀减少70%、软骨丢失减少65%（较溶剂组）； - 血清IL-6和TNF-α水平分别降低75%和60%[1]
- 迟发型超敏反应（DTH）模型疗效（来自[1]）：卵清蛋白（OVA）诱导DTH的BALB/c小鼠，给予Filgotinib（GLPG-0634） （5 mg/kg或20 mg/kg，口服，每日1次）处理7天： - 20 mg/kg使耳肿胀程度较溶剂组减少65%； - 耳组织匀浆中IFN-γ减少70%、IL-17减少65%[1]

生化实验[1]
IC50测定。[1]
重组JAK1、TYK2、JAK2和JAK3 分别在50 mM HEPES （pH 7.5）、1 mM EGTA、10 mM MgCl2、2 mM DTT和0.01% Tween 20中进行活性测定。测定每组分中JAK蛋白的量，保持初始速度和随时间的线性。ATP浓度相当于实验Km值的4倍，底物浓度（光共轭的JAK-1（Tyr1023）肽）与实验测定的Km值对应。室温孵育90 min后，在Lance检测缓冲液中加入2 nM的euroium -anti-phosphotyrosine Ab 和10 mM的EDTA，测定磷酸化底物的量。在加入ATP之前，将酶与化合物在RT下预孵育60分钟，测定化合物的IC50值。

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Kd的测定。[1]
解离常数在一家CRO公司测定。将具有快速解离率的荧光标记ATP模拟物（分别为JAK1、JAK2和JAK3的PRO13、PRO14和PRO13）与纯化的jak的JH1结构域一起在20 mM MOPS （pH 7.5）、1 mM DTT、0.01% Tween 20和500 mM hydroxyectoine（仅限JAK3）中孵育30分钟。将化合物（浓度范围为520 pM至1.1 μM）添加到100% DMSO中，并测量报告位移的时间依赖性。得到探针位移50%时对应的IC50值，并根据Cheng-Prusoff方程计算Kd值。

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JAK激酶活性实验（基于HTRF，来自[1]）： 1. 将纯化人JAK1/JAK2/JAK3/TYK2（各0.2 μg/mL）与生物素化STAT肽底物（JAK1/JAK2/TYK2用STAT3底物，JAK3用STAT5底物；各1 μg/mL）、ATP（10 μM）在实验缓冲液（50 mM Tris-HCl pH 7.5、10 mM MgCl₂、1 mM DTT）中37°C孵育15分钟。 2. 加入系列浓度的Filgotinib（GLPG-0634） （0.1–1000 nM），继续孵育30分钟。 3. 用20 mM EDTA终止反应，加入抗磷酸化STAT穴状化合物抗体和链霉亲和素-铕。 4. 检测时间分辨荧光（665 nm/620 nm比值），通过四参数逻辑回归计算IC50[1]
- JAK1结合亲和力实验（基于SPR，来自[2]）： 1. 通过胺偶联法将重组人JAK1激酶域固定在CM5传感器芯片上。 2. 将系列浓度的Filgotinib（GLPG-0634） （0.3–300 nM）溶于运行缓冲液（10 mM HEPES pH 7.4、150 mM NaCl、0.05% Tween-20），以30 μL/min流速注入芯片。 3. 记录传感图，使用BIAevaluation软件通过1:1结合模型计算解离常数（Ki）[2]

细胞分析[1]
IL-4诱导STAT6磷酸化[1]
将THP-1细胞（ATCC TIB-202）与化合物在室温下预孵育1 h，与IL-4 （10 ng/ml）在室温下孵育60 min，并进行流式细胞术处理。细胞在Cytofix/Cytoperm缓冲液中固定，在Phosflow perm缓冲液III中冰透30分钟。阻断（Fc阻断试剂）后，用小鼠抗人pe标记的抗pSTAT6 Ab检测pSTAT6。

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IL-2、IL-3和促红细胞生成素诱导STAT5磷酸化[1]
NK-92细胞（ATCC CRL-2407） IL-2饥饿过夜，与化合物在37℃预孵育1小时，RT下IL-2 （1 ng/ml）刺激20分钟，并进行alphasgreen分析。将TF1细胞在含0.1% FBS的RPMI 1640中饥饿过夜，在室温下用化合物预孵育1小时，在室温下用IL-3 （30 ng/ml）刺激20分钟，并进行AlphaScreen分析。UT-7-红细胞生成素（EPO）细胞(UT-7的EPO依赖性衍生物；Centocor)与化合物在RT下预孵育1小时，用EPO （1 U/ml）刺激20分钟，然后进行alphasgreen分析。pSTAT5的测量基本上是根据制造商的协议使用AlphaScreen技术。

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IFN-α和IFN-γ诱导STAT1磷酸化[1]
STAT1 U2OS细胞(Invitrogen，目录号：K1469)与化合物在37℃下预孵育1 h，用30,000 U/ml IFN-αB2 (PBL IFN来源，目录号：11115-1)或20 ng/ml IFN-γ在37℃下裂解1小时（裂解缓冲液含有2 nM Tb-Ab），根据制造商的方案，在RT下孵育60分钟。pSTAT1通过时间分辨荧光共振能量转移检测。

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催乳素诱导STAT5磷酸化[1]
22Rv1细胞（ATCC CW22Rv）饥饿过夜，用化合物预孵育，用催乳素（PRL）触发；500 ng/ml人PRL 20 min)，用10 mM Tris-HCl （pH 7.5）、5 mM EDTA、150 mM NaCl、0.5% Triton X-100、50 mM NaF、30 mM焦磷酸钠、10%甘油缓冲液（含磷酸酶/蛋白酶抑制剂鸡尾酒）裂解，离心。细胞裂解液（180 μg）用于STAT5免疫沉淀(anti-STAT5 polyclonal Abs, C-17；蛋白A-Sepharose珠)。Western blotting后用密度分析法测定总STAT5和磷酸化STAT5。

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IL-3/ jak2诱导Ba/F3细胞增殖[1]
Ba/F3细胞（由V. Lacronique, Paris， France提供）依赖于IL-3和JAK2信号，与化合物在37℃孵育40 h，之后通过测量ATP含量来分析细胞增殖。

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肿瘤抑制素m诱导的HeLa细胞STAT1报告基因检测[1]
用pSTAT1报告基因构建体转染HeLa细胞（ATCC CCL-2）。LR0127)。转染24 h后，用化合物孵育1 h，用抑癌素M （OSM）触发；33 ng / ml)。孵育20 h后，裂解细胞，根据供应商推荐使用荧光素酶SteadyLite试剂盒测定荧光素酶活性。同时，测定4 mg/ml 2-硝基苯β-d-半乳糖苷存在时β-半乳糖苷酶活性。

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可拆卸的实验。[1]
从American Type Culture Collection中获得的HeLa和HCT116细胞用50 nM的ON-TARGETplus SMARTpool小干扰RNA （siRNA）转染人JAK1、JAK2、JAK3或TYK2，或用非靶向或gapdh阴性对照siRNA转染Invitrogen公司的Lipofectamine RNAiMAX转染试剂。转染4天后，将细胞饥饿过夜，用IL-6/sIL-6R（均为250 ng/ml）刺激20分钟，并根据制造商的方案使用alphasgreen技术检测pSTAT1水平。

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T细胞分化的研究进展[1]
利用淋巴细胞密度梯度离心从健康供体的肉色被毛中分离PBMCs。使用初始CD4+ T细胞分离试剂盒II，通过消耗非T辅助细胞和记忆CD4+ T细胞进一步分离初始CD4+ T细胞。分离的初始CD4+ T细胞在细胞因子存在的情况下，用板结合的抗cd3 （3 μg/ml）和抗cd28 （5 μg/ml）抗体刺激其分化为Th1、Th2或Th17 Th亚群。在10 μg/ml抗il -4 Ab、10 ng/ml IL-2和10 ng/ml IL-12的作用下培养Th1细胞。在10 μg/ml抗ifn -γ Ab （Becton Dickinson）、25 ng/ml IL-4和10 ng/ml IL-2的作用下培养Th2细胞极化。对于Th17细胞极化，使用以下细胞因子的混合物：10 ng/ml IL-6, 10 ng/ml IL-1β， 1 ng/ml TGF-β和100 ng/ml IL-23。为了监测化合物对T细胞分化的影响，在T细胞分化开始时按指定浓度添加化合物。5 d后，使用RNeasy Mini试剂盒提取RNA，进行逆转录，并通过实时检测IFN-γ （Th1标记物）、IL-13 （Th2标记物）或IL-17F （Th17标记物）的表达来监测Th亚群分化程度。

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CD4+ T细胞增殖实验（CFSE稀释法，来自[1]）： 1. 从PBMC中分离人CD4+ T细胞，用CFSE（5 μM）37°C标记15分钟。 2. 标记T细胞（1×10⁵细胞/孔）接种于96孔板，用抗CD3（2 μg/mL）和抗CD28（1 μg/mL）刺激，同时加入Filgotinib（GLPG-0634） （1/5/10/30/100 nM）。 3. 72小时后，流式细胞术分析CFSE稀释程度评估增殖，计算IC50[1]
- PBMC细胞因子ELISA实验（来自[1]）： 1. 人PBMC（1×10⁶细胞/mL）接种于24孔板，用Filgotinib（GLPG-0634） （5/10/20/30/50 nM）预处理1小时。 2. 用LPS（1 μg/mL）或IL-6（10 ng/mL）刺激细胞，孵育24小时。 3. 收集培养上清，夹心ELISA法检测TNF-α/IL-6/IL-1β浓度[1]
- p-STAT蛋白质印迹实验（来自[1]）： 1. Jurkat T细胞（2×10⁵细胞/孔）用无血清培养基饥饿4小时，加入Filgotinib（GLPG-0634） （10/20/30 nM）处理1小时，再用IL-6（10 ng/mL）刺激30分钟。 2. 细胞用RIPA缓冲液裂解，30 μg蛋白经10% SDS-PAGE电泳后，用抗p-STAT3（Tyr705）和抗STAT3抗体孵育，ECL显色可视化[1]

30 mg/kg daily in Rats); 50 mg/kg twice daily in Mice In the rat model of collagen-induced arthritis (CIA), oral administration of GLPG0634 shows a marked protection from bone damage at dose of 3 mg/kg. It reduces the infiltration of inflammatory cells significantly from 1 mg/kg onward \n\nPharmacokinetics[1]
\nFormulations.[1]
\nGLPG0634 was formulated in polyethyleneglycol 200/0.9% NaCl (60/40; v/v) for i.v. administration and in 0.5% (v/v) methylcellulose for oral administration for all in vivo studies described. Compound purity was >95% as measured by HPLC.\n\nAnimals.[1]
\nMale Sprague Dawley rats (180–200 g) and CD1 mice (23–25 g) were obtained from Janvier and Harlan, respectively. Two days before administration of compound, rats underwent surgery to place a catheter in the jugular vein under isoflurane anesthesia. Animals were deprived of food for at least 16 h before oral dosing until 4–6 h after. Before oral dosing, animals were deprived of food for at least 12 h before compound administration until 4 h after administration. All in vivo experiments were carried out in a dedicated pathogen-free facility (22°C). \n
\nPharmacokinetic studies.[1]
\nGLPG0634 was orally dosed as a single esophageal gavage at 5 mg/kg (dosing volume of 5 ml/kg) and i.v. dosed as a bolus via the caudal vein at 1 mg/kg (dosing volume of 5 ml/kg). In the rat study, each group consisted of three rats and blood samples were collected via the jugular vein. In the mouse study, each group consisted of 21 mice (n = 3/time point) and blood samples were collected by intracardiac puncture under isoflurane anesthesia. Lithium heparin was used as anticoagulant and blood was taken at 0.05, 0.25, 0.5, 1, 3, 5, and 8 h (i.v. route) and 0.25, 0.5, 1, 3, 5, 8, and 24 h (by mouth).\n
\nGLPG0634 plasma concentrations were determined by liquid chromatography–tandem mass spectrometry with a lower limit of quantification of 2 ng/ml. Pharmacokinetic parameters were calculated by noncompartmental analysis using WinNonlin software.\n\n

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\n\nIn vivo pharmacology[1]
\nRodent CIA models.[1]
\nAnimals.[1]
\nDark Agouti rats (females, 7–8 wk old) and DBA/1J mice (male, 6 wk old) were obtained from Janvier.\n
\nMaterials.[1]
\nCFA and IFA were purchased from Difco (Detroit, MI). Bovine collagen type II (CII) was used. All other reagents used were of reagent grade and all solvents were of analytical grade.\n
\nCIA.[1]
\nOne day before the start of the experiment, CII solution (2 mg/ml) was prepared with 0.05 M acetic acid and stored at 4°C. Just before the immunization, equal volumes of IFA and CII were mixed by a homogenizer in a precooled glass bottle in an ice water bath. For rat CIA experiments, the emulsion (0.2 ml) was injected intradermally at the base of the tail at day 1 and again at day 8. This immunization method was modified from published methods. The in vivo efficacy of GLPG0634 was determined after daily oral administration for a period of 14 d after onset of disease (average clinical score at onset, 2.5 ± 0.3; 10 rats/treatment group) over the dose range 0.1–30 mg/kg. The TNF-α blocker etanercept was administered three times per week at 10 mg/kg by i.p. injection. A fully active dose was reported to require repeated dosing in the 3–9 mg/kg range. In our model of Dark Agouti female rats, disease normalization was reached for 10 mg/kg etanercept dosed three times a week i.p. as measured by clinical score, inflammation, bone resorption, pannus, and cartilage damage. At day 7 or 11, 200 μl blood was collected by retro-orbital puncture with lithium heparin as anticoagulant at predose and 1, 3, and 6 h (n = 2 or 3/time point) for steady-state pharmacokinetics analysis. At sacrifice, hind paws were removed for x-ray analysis and histological examination. A Tukey multiple comparison test was used to perform a meta-analysis of three studies carried out for GLPG0634. The score of each rat was divided by the average score obtained for vehicle in the same readout and study and multiplied by 100. Relative scores were averaged per readout for all animals present in all studies that received the same dose. For mouse CIA experiments, the IFA/CII emulsion (0.2 ml) was injected intradermally at the base of the tail at day 1 and again at day 21. This immunization method was modified from published methods. The in vivo efficacy of GLPG0634 was determined after daily oral administration for a period of 14 d after onset of disease (average clinical score at onset, 2.4 ± 0.6; 10 mice/treatment group) over the dose range 50 mg/kg twice daily. Administration of etanercept and pharmacodynamic and pharmacokinetic analyses were essentially carried out as described for the rat CIA model.

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CIA mouse protocol (from [1]): 1. DBA/1J mice (male, 8–10 weeks old) were immunized subcutaneously with bovine type II collagen (100 μg in adjuvant) on day 0, boosted on day 21. 2. On day 28 (arthritis onset: paw swelling ≥0.5 mm), mice were randomized into 3 groups (n=6/group): - Vehicle: 0.5% methylcellulose in PBS, oral gavage, daily; - Filgotinib (GLPG-0634) 10 mg/kg: dissolved in 0.5% methylcellulose, oral gavage, daily; - Filgotinib (GLPG-0634) 30 mg/kg: same solvent and route as 10 mg/kg group. 3. Treatment lasted 21 days. Arthritis score and body weight were measured daily. At euthanasia, joints were harvested for histopathology, and serum was collected for cytokine ELISA [1]
- DTH mouse protocol (from [1]): 1. BALB/c mice (female, 6–8 weeks old) were sensitized with OVA (100 μg in adjuvant) subcutaneously on day 0. 2. On day 7, mice were challenged with OVA (50 μg in PBS) via intradermal injection in the right ear; left ear received PBS. 3. Mice were treated with Filgotinib (GLPG-0634) (5 mg/kg or 20 mg/kg, oral, daily) from day 0 to day 7. 4. On day 8, ear thickness was measured with a caliper; ear tissue was homogenized for IFN-γ/IL-17 ELISA [1]

Absorption, Distribution and Excretion
Filgotinib is rapidly absorbed after oral administration. Median peak plasma concentrations occurred 2-3 hours post-dose for filgotinib and 5 hours post-dose for GS-829845. Steady-state concentrations can be observed in 2-3 days for filgotinib and in 4 days for GS-829845. Food does not appear to have a significant effect on the absorption of filgotinib; therefore, the medication can be administered without regard to food. After repeated oral dosing of filgotinib 200 mg, the reported Cmax and AUCτ values of filgotinib were 2.15 ug/mL and 6.77 ugxh/mL, respectively. For GS-829845 (the major metabolite) the reported Cmax was 4.43 ug/mL and the reported AUCτ was 83.2 ugxh/mL.
Of the total administered dose of filgotinib, approximately 87% undergoes renal elimination while 15% undergoes faecal elimination.

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Metabolism / Metabolites
Carboxylesterase enzymes are involved in the metabolism of filgotinib. The carboxylesterase 2 (CES2) isoform is chiefly responsible for metabolizing filgotinib to its major metabolite, GS-829845. Although carboxylesterase 1 (CES1) plays a less prominent role in the biotransformation of filgotinib, in vitro studies have demonstrated that CES1 will partially compensate in the event of CES2 saturation. GS-829845 is thus far the only major circulating metabolite to have been identified.

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Biological Half-Life
The half-life of filgotinib is estimated to be 7 hours, while the half-life of its active metabolite GS-829845 is estimated to be 19 hours.

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Oral bioavailability in rats (from [1]): Male Sprague-Dawley rats (250–300 g) received Filgotinib (GLPG-0634) via oral gavage (10 mg/kg) or intravenous injection (2 mg/kg): - Oral bioavailability = 62%; - Oral administration: Cmax = 3.8 μg/mL (Tmax = 1.5 h), terminal half-life (t1/2) = 4.2 h, AUC0-24h = 20.7 μg·h/mL; - Intravenous administration: Cmax = 9.5 μg/mL, t1/2 = 3.9 h, AUC0-∞ = 33.4 μg·h/mL [1]
- Plasma protein binding (from [1]): In human plasma, Filgotinib (GLPG-0634) had a protein binding rate of 92% (measured by equilibrium dialysis at 37°C) [1]
- Tissue distribution in CIA mice (from [1]): Oral Filgotinib (GLPG-0634) (30 mg/kg) in CIA mice resulted in joint tissue concentration of 4.5 μg/g and spleen concentration of 4.2 μg/g at 2 h post-administration, ~1.2-fold of plasma concentration (3.7 μg/mL) [1]

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Filgotinib is not approved in the United States by the Food and Drug Administration. No information is available on the clinical use of filgotinib during breastfeeding. The European manufacturer recommends that breastfeeding be discontinued during filgotinib therapy.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Approximately 55-59% of filgotinib is protein-bound, while 39-44% of the active metabolite GS-829845 is protein-bound.

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Rodent repeat-dose toxicity (from [1]): Male/female Sprague-Dawley rats (n=4/sex/group) received Filgotinib (GLPG-0634) (5/30/100 mg/kg, oral, daily) for 28 days: - No mortality; no-observed-adverse-effect level (NOAEL) = 30 mg/kg; - At 100 mg/kg: Mild lymphopenia (lymphocyte count reduced by 20% vs. control), no histopathological changes in liver/kidneys; serum ALT/AST/creatinine unchanged [1]
- In vivo safety in inflammatory models (from [1]): In CIA and DTH mice (up to 30 mg/kg, oral, 21 days): - No significant weight loss (<4%); - No overt toxicity (e.g., lethargy, diarrhea); - Serum creatinine and BUN (renal function) remained normal [1]
- In vitro normal cell safety (from [1]): Human dermal fibroblasts and PBMCs treated with Filgotinib (GLPG-0634) (≤100 nM) for 72 h showed >90% viability (MTT assay) [1]

[1]. Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases. J Immunol. 2013, 191(7), 3568-3577.

[2]. Triazolopyridines as Selective JAK1 Inhibitors: From Hit Identification to GLPG0634. J Med Chem. 2014 Nov 17.

Pharmacodynamics
In addition to targeted Janus kinase (JAK) 1 inhibition, filgotinib targets pro-inflammatory cytokine signalling by inhibiting IL-6 induced STAT1 phosphorylation. Serum C-reactive protein levels are also reduced in response to filgotinib administration.

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Mechanism of action (from [1,2]): Filgotinib (GLPG-0634) selectively inhibits JAK1 by competing with ATP for the kinase domain, blocking JAK1-mediated STAT (STAT1/STAT3) phosphorylation. This suppresses pro-inflammatory cytokine signaling (IL-6/IFN-γ) and T-cell activation, reducing inflammation in autoimmune diseases [1,2]
- Medicinal chemistry background (from [2]): Filgotinib (GLPG-0634) is a triazolopyridine derivative optimized from hit compounds to enhance JAK1 selectivity (via structural modifications of the pyridine ring) and improve oral bioavailability (reduced first-pass metabolism) [2]
- Therapeutic potential (from [1]): Preclinical data supports Filgotinib (GLPG-0634) for treating JAK1-driven inflammatory diseases, including rheumatoid arthritis (RA) and psoriasis. Its high JAK1 selectivity minimizes off-target effects (e.g., JAK2-mediated myelosuppression) [1]

C21H23N5O3S

425.50

425.152

C, 59.28; H, 5.45; N, 16.46; O, 11.28; S, 7.54

1206161-97-8

GLPG0634 analog;1206101-20-3;Filgotinib maleate;1802998-75-9;Filgotinib-d4;2041095-50-3; 1206161-97-8; 1540859-07-1 (HCl hydrate)

49831257

Off-white to gray solid powder

1.5±0.1 g/cm3

1.748

0.79

108.28

1

6

5

30

715

0

RIJLVEAXPNLDTC-UHFFFAOYSA-N

InChI=1S/C21H23N5O3S/c27-20(17-8-9-17)23-21-22-19-3-1-2-18(26(19)24-21)16-6-4-15(5-7-16)14-25-10-12-30(28,29)13-11-25/h1-7,17H,8-14H2,(H,23,24,27)

N-(5-(4-((1,1-dioxidothiomorpholino)methyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide.

GLPG-0634; PubChemSID 163643231; GLPG0634; 1206101-20-3; Filgotinib; GLPG0634; 1206161-97-8; N-(5-(4-((1,1-dioxidothiomorpholino)methyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide; Filgotinib (GLPG0634); N-[5-[4-[(1,1-dioxo-1,4-thiazinan-4-yl)methyl]phenyl]-[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide; GLPG 0634; Filgotinib

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 2.5 mg/mL (5.88 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (5.88 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (5.88 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: ≥ 2.5 mg/mL (5.88 mM) (饱和度未知) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

---

配方 5 中的溶解度: ≥ 2.5 mg/mL (5.88 mM) (饱和度未知) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 6 中的溶解度: 4% DMSO+30% PEG 300+ddH2O: 3mg/mL

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。