| 规格 | 价格 | 库存 | 数量 |
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| 10 mM * 1 mL in DMSO |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| Other Sizes |
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| 靶点 |
Bruton Tyrosine Kinase (BTK) (recombinant human BTK, IC50 = 1.1 nM); >300-fold selectivity over EGFR (IC50 = 350 nM), ITK (IC50 = 420 nM), JAK3 (IC50 = 480 nM); no activity against Src, Abl, VEGFR2 (IC50 > 1000 nM) [1]
- Confirmed BTK as primary target (platelet microparticle model; consistent with [1]’s IC50) [2] - Confirmed BTK targeting (lupus nephritis model; no additional IC50 values) [3] |
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| 体外研究 (In Vitro) |
单核细胞中 Fcγ 受体接合介导的肿瘤坏死因子 α 产生 (IC50 = 7 nM)、肥大细胞中 Fcε 受体交联诱导的脱粒 (IC50 = 2.9 nM) 以及 B 细胞抗原受体诱导的激活标记物表达，全血 B 细胞中的 CD69 (IC50 = 21 nM) 均被 RN486 阻断[1]。在包括人原代滑膜 FLS 和活化的人血小板的共培养系统中，惊厥素刺激导致促炎细胞因子 IL-6 和 IL-8 的产生增加。这种效应受到 RN486 剂量依赖性抑制[2]。
抑制B细胞介导的免疫反应：15 nM RN486处理小鼠脾B细胞72小时，抗IgM诱导的增殖减少90%；B细胞活化标志物CD69、CD86分别降低88%、85%（流式细胞术）[1] - 阻断血小板微粒（PMP）生成：50 nM RN486处理人血小板30分钟，胶原诱导的PMP释放减少78%；活化血小板中p-BTK（Tyr223）降低92%（Western blot检测）[2] - 抑制肾小球炎症反应：200 nM RN486处理小鼠肾小球系膜细胞24小时，LPS诱导的TNF-α/IL-6分泌减少75%/70%；NF-κB p65核转位抑制80%（免疫荧光）[3] |
| 体内研究 (In Vivo) |
在大鼠佐剂诱导关节炎 (AIA) 和小鼠 CIA 模型中，RN486 具有很强的抗炎和骨保护特性。在 AIA 模型中，RN486 (1–30 mg/kg) 可以减少爪子水肿和血液中的炎症标志物，这也可以减少关节和全身炎症[1]。
大鼠被动皮肤过敏（PCA）模型（[1]）：口服RN486（10 mg/kg/天）持续7天，耳肿胀较溶剂组减少72%；皮肤组胺含量降低68%[1] - 小鼠胶原诱导关节炎（CIA）模型（[1]）：口服RN486（25 mg/kg/天）持续21天，关节炎评分从溶剂组8.3降至2.2；关节炎症细胞浸润减少75%（组织病理学）[1] - 狼疮倾向NZB×NZW小鼠模型（[3]）：口服RN486（20 mg/kg/天）持续12周，蛋白尿较溶剂组减少70%；血清抗dsDNA抗体降低65%；肾小球硬化评分从3.8降至1.2[3] - 小鼠血小板依赖炎症模型（[2]）：单次口服RN486（30 mg/kg），给药后4小时胶原诱导的腹腔PMP水平减少70%[2] |
| 酶活实验 |
BTK激酶活性实验[1]：重组人BTK激酶结构域（50 ng/孔）与RN486（0.01-100 nM）在反应缓冲液（25 mM HEPES pH 7.5，10 mM MgCl₂，1 mM DTT，0.1 mM 钒酸钠）中于37°C孵育20分钟。加入10 μM ATP和荧光标记肽底物（序列：biotin-GGEEEEYFELVAKKKK），30°C继续孵育60分钟。链霉亲和素包被的96孔板捕获磷酸化底物，抗磷酸酪氨酸抗体检测，均相时间分辨荧光（HTRF，激发光340 nm，发射光665 nm）定量激酶活性；非线性回归分析计算IC50[1]
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| 细胞实验 |
小鼠B细胞活化实验[1]：从C57BL/6小鼠分离脾B细胞，接种于96孔板（4×10³个/孔）。RN486（0.1 nM-1 μM）预处理1小时后，抗小鼠IgM（10 μg/mL）刺激72小时。[³H]-胸腺嘧啶掺入法检测增殖；FITC标记抗体流式分析CD69/CD86表达[1]
- 人血小板PMP实验[2]：人血小板（2×10⁸个/mL）用RN486（5-200 nM）预处理15分钟，胶原（2 μg/mL）刺激30分钟。离心（10,000×g，30分钟）分离PMP，CD41a（血小板标志物）抗体流式定量[2] - 肾小球系膜细胞实验[3]：小鼠肾小球系膜细胞接种于24孔板（1×10⁵个/孔），RN486（50-200 nM）处理2小时后，LPS（1 μg/mL）刺激24小时。收集上清液，ELISA检测TNF-α/IL-6；Alexa Fluor 488标记抗p65抗体免疫荧光观察NF-κB p65核转位[3] |
| 动物实验 |
Rodent models
Rat PCA model (Sprague-Dawley rats, [1]): Rats were intradermally injected with anti-DNP IgE (1 μg/site) on ears. 24 hours later, rats received RN486 (10 mg/kg/day, oral gavage) for 7 days, then challenged with DNP-BSA (1 mg/mL) via tail vein. Ear swelling was measured via caliper; skin histamine was quantified via HPLC. Drug was dissolved in 0.5% methylcellulose + 0.2% Tween 80 [1] - Mouse CIA model (C57BL/6 mice, [1]): Arthritis was induced by intradermal injection of bovine type II collagen (200 μg/mouse). 14 days post-induction, mice received RN486 (25 mg/kg/day, oral gavage) for 21 days. Drug was dissolved in 0.5% methylcellulose; arthritis score (0-10, based on joint redness/swelling) was recorded every 3 days [1] - NZB×NZW lupus model ([3]): 12-week-old female NZB×NZW mice were randomized to vehicle or RN486 groups. RN486 (20 mg/kg/day, oral gavage) was administered for 12 weeks. Drug was dissolved in 0.5% methylcellulose; proteinuria was measured weekly via urine dipstick; serum anti-dsDNA antibodies were detected via ELISA at study end [3] |
| 药代性质 (ADME/PK) |
In mice (literature 1): Oral bioavailability of RN486 = 60% (25 mg/kg dose); plasma half-life (t₁/₂) = 4.5 hours; maximum plasma concentration (Cmax) = 5.1 μM at 1.3 hours post-oral administration [1]
- In rats (literature 1): Intravenous administration (10 mg/kg) showed a clearance rate of 11 mL/min/kg; volume of distribution at steady state (Vss) = 1.0 L/kg [1] - Plasma protein binding: 99.5% binding to human plasma proteins (measured via ultrafiltration method) [1] |
| 毒性/毒理 (Toxicokinetics/TK) |
In 21-day CIA study ([1]): No significant weight loss (>8%); serum ALT (27 ± 4 U/L), AST (51 ± 6 U/L), BUN (18 ± 3 mg/dL) were within normal ranges [1]
- In 12-week lupus study ([3]): 1/10 mice showed mild gastrointestinal discomfort (resolved by day 14); no histopathological changes in liver, kidney, or spleen [3] - In 7-day PCA study ([2]): No treatment-related mortality; peripheral blood platelet count remained normal (1.8 ± 0.2×10⁹/L vs. vehicle 1.9 ± 0.3×10⁹/L) [2] |
| 参考文献 |
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| 其他信息 |
RN486 is a selective, reversible Bruton Tyrosine Kinase (BTK) inhibitor that blocks BTK activation by competing with ATP for binding to the kinase active site [1]
- Its therapeutic potential spans B-cell-mediated autoimmune diseases, including allergic hypersensitivity, rheumatoid arthritis, and lupus nephritis, via inhibiting B-cell activation, platelet inflammatory responses, and glomerular inflammation [1][2][3] - Preclinical data confirm its ability to reduce autoantibody production (e.g., anti-dsDNA) and organ damage (e.g., glomerular sclerosis) in lupus models, supporting its role in treating systemic autoimmune disorders [3] |
| 分子式 |
C35H35FN6O3
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|---|---|---|
| 分子量 |
606.69
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| 精确质量 |
606.275
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| CAS号 |
1242156-23-5
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| 相关CAS号 |
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| PubChem CID |
46908026
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| 外观&性状 |
Off-white to light yellow solid powder
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| 密度 |
1.4±0.1 g/cm3
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| 沸点 |
868.6±65.0 °C at 760 mmHg
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| 闪点 |
479.1±34.3 °C
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| 蒸汽压 |
0.0±0.3 mmHg at 25°C
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| 折射率 |
1.696
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| LogP |
2.95
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| tPSA |
95.63
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| 氢键供体(HBD)数目 |
2
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| 氢键受体(HBA)数目 |
8
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| 可旋转键数目(RBC) |
7
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| 重原子数目 |
45
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| 分子复杂度/Complexity |
1210
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| 定义原子立体中心数目 |
0
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| InChi Key |
ZTUJNJAKTLHBEX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C35H35FN6O3/c1-39-12-14-41(15-13-39)26-8-9-32(37-19-26)38-30-18-25(20-40(2)34(30)44)27-4-3-5-31(28(27)21-43)42-11-10-23-16-24(22-6-7-22)17-29(36)33(23)35(42)45/h3-5,8-11,16-20,22,43H,6-7,12-15,21H2,1-2H3,(H,37,38)
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| 化学名 |
6-cyclopropyl-8-fluoro-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-2H-isoquinolin-1-one
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| 别名 |
RN-486; RN 486; RN486;
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| HS Tariff Code |
2934.99.9001
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| 存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| 溶解度 (体外实验) |
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| 制备储备液 | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6483 mL | 8.2414 mL | 16.4829 mL | |
| 5 mM | 0.3297 mL | 1.6483 mL | 3.2966 mL | |
| 10 mM | 0.1648 mL | 0.8241 mL | 1.6483 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液)：对于大多数产品，InvivoChem推荐用DMSO配置母液 (比如：5、10、20mM或者10、20、50 mg/mL浓度），个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息，或者很难将产品溶解在溶液中，请联系我们;
3、建议使用下列计算器进行相关计算（摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等）;
4、母液配好之后，将其分装到常规用量，并储存在-20°C或-80°C，尽量减少反复冻融循环。
计算结果:
工作液浓度： mg/mL；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度，请首先与我们联系。
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH2O，混匀澄清。
(1) 请确保溶液澄清之后，再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶；
(2) 一定要按顺序加入溶剂 (助溶剂) 。
Inhibitory effect of RN486 on the effector phase of immune arthritis in mice.J Pharmacol Exp Ther.2012 Apr;341(1):90-103. |
Anti-inflammatory and disease-modifying effects of RN486 in the rat AIA model.J Pharmacol Exp Ther.2012 Apr;341(1):90-103. |
Additive inhibitory effects of RN486 and MTX on inflammation and bone erosions in the rat AIA model.J Pharmacol Exp Ther.2012 Apr;341(1):90-103. |
BTK-IN-40
Btk substrate peptide
WS-11
BTK-IN-38
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