Belumosudil mesylate
(Synonyms: KD025 mesylate; SLx-2119 mesylate) 目录号 : GC26330Belumosudil mesylate是一种选择性的ROCK2抑制剂，对ROCK2的IC50值为105nM，对ROCK1的IC50值为24µM。
Cas No.:2109704-99-4
Sample solution is provided at 25 µL, 10mM.
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Belumosudil mesylate is a selective ROCK2 inhibitor, with IC50 values of 105nM for ROCK2 and 24µM for ROCK1[1]. ROCK2 is a critical regulator of immune modulation and fibrosis[2].The selective inhibitor of ROCK2 belumosudil mesylate can reduces fibrosis by downregulating both transforming growth factor-β signaling and profibrotic gene expression and usually be utilized in research on chronic graft-versus-host disease (cGVHD)[3][4]. Additionally, belumosudil mesylate can also be used for research in other immune-related diseases such as systemic sclerosisue to its anti-inflammatory and antifibrotic activities[5].
In vitro, treatment of cardiac fibroblasts(CFs) with different concentrations of belumosudil mesylate (0.625, 1.25, 2.5 and 5μM) for 24h after serum starvation for 24h selectively inhibits ROCK2 and reduces the phosphorylation of Smad2 in a dose-dependent manner[6]. Treatment of PASMC cells with belumosudil mesylate ( 40µM; 24h) induces significant down-regulations of Tsp-1 and CTGF mRNA levels[1].
In vivo, belumosudil mesylate(100, 200 or 300mg/kg) was administered every 12h via orogastric gavage for a total of five doses to young adult (C57BL/6, 2–3 months old, male 22–30g, female 16–23g), aged (C57BL/6, 12 months old, 33–52g), or type 2 diabetic mice，it dose-dependently reduces infarct volume after transient middle cerebral artery occlusion,and it is at least as efficacious in aged, diabetic or female mice, as in normal adult males[7].
References:
[1] Boerma, M., Fu, Q., Wang, J., Loose, D. S., Bartolozzi, A., Ellis, J. L., McGonigle, S., Paradise, E., Sweetnam, P., Fink, L. M., Vozenin-Brotons, M. C., & Hauer-Jensen, M. (2008). Comparative gene expression profiling in three primary human cell lines after treatment with a novel inhibitor of Rho kinase or atorvastatin. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis, 19(7), 709–718.
[2] Zanin-Zhorov, A., & Blazar, B. R. (2021). ROCK2, a critical regulator of immune modulation and fibrosis has emerged as a therapeutic target in chronic graft-versus-host disease. Clinical immunology (Orlando, Fla.), 230, 108823.
[3] N., Toyosaki, M., Katayama, Y., Murayama, S., Sasagawa, Y., Maeda, Y., Hatake, K., & Teshima, T. (2024). An open-label study of belumosudil, a selective ROCK2 inhibitor, as second or subsequent line of therapy for steroid-dependent/steroid-resistant chronic GVHD. American journal of hematology, 99(10), 1917–1926.
[4] Taylor, B., Cohen, J., Tejeda, J., & Wang, T. P. (2022). Belumosudil for chronic graft-versus-host disease. Drugs of today (Barcelona, Spain : 1998), 58(5), 203–212.
[5] Gunes, I., Bernstein, E., Cowper, S. E., Panse, G., Pradhan, N., Camacho, L. D., Page, N., Bundschuh, E., Williams, A., Carns, M., Aren, K., Fantus, S., Volkmann, E. R., Bukiri, H., Correia, C., Wang, R., Kolachalama, V., Wilson, F. P., Mawe, S., Mahoney, J. M., … Hinchcliff, M. (2024). Neural network analysis as a novel skin outcome in a trial of belumosudil in patients with systemic sclerosis. Research square, rs.3.rs-4889334.
[6] Liu, Q., Li, H. Y., Wang, S. J., Huang, S. Q., Yue, Y., Maihemuti, A., Zhang, Y., Huang, L., Luo, L., Feng, K. N., & Wu, Z. K. (2022). Belumosudil, ROCK2-specific inhibitor, alleviates cardiac fibrosis by inhibiting cardiac fibroblasts activation. American journal of physiology. Heart and circulatory physiology, 323(1), H235–H247.
[7] Lee, J. H., Zheng, Y., von Bornstadt, D., Wei, Y., Balcioglu, A., Daneshmand, A., Yalcin, N., Yu, E., Herisson, F., Atalay, Y. B., Kim, M. H., Ahn, Y. J., Balkaya, M., Sweetnam, P., Schueller, O., Poyurovsky, M. V., Kim, H. H., Lo, E. H., Furie, K. L., & Ayata, C. (2014). Selective ROCK2 Inhibition In Focal Cerebral Ischemia. Annals of clinical and translational neurology, 1(1), 2–14.
Belumosudil mesylate是一种选择性的ROCK2抑制剂，对ROCK2的IC50值为105nM，对ROCK1的IC50值为24µM[1]。ROCK2 是免疫调节和纤维化过程中的关键调控因子[2]。Belumosudil mesylate 是一种选择性的 ROCK2 抑制剂，通过下调转化生长因子-β（TGF-β）信号通路和促纤维化基因的表达来减少纤维化，通常用于慢性移植物抗宿主病（cGVHD）的研究[3][4]。此外，因其具有抗炎和抗纤维化活性，Belumosudil mesylate 还可以用于系统性硬化症等其他免疫相关疾病的研究[5]。
在体外实验中，心肌成纤维细胞（CFs）在血清饥饿24小时后，用不同浓度的 Belumosudil mesylate（0.625、1.25、2.5 和 5μM）处理24小时，能够选择性抑制 ROCK2，并以剂量依赖性方式减少 Smad2 的磷酸化[6]。在肺动脉平滑肌细胞（PASMC）中，用 Belumosudil mesylate（40μM，处理24小时）处理可显著下调 Tsp-1 和 CTGF mRNA 水平[1]。
在体内实验中，Belumosudil mesylate（100、200 或 300 mg/kg）每12小时通过口胃管给药共5次，用于年轻成年（C57BL/6，2-3个月龄，雄性22-30克，雌性16-23克）、老年（C57BL/6，12个月龄，33-52克）或2型糖尿病小鼠，Belumosudil mesylate 剂量依赖性地减少短暂性中脑动脉阻塞后的梗死体积，并且在老年、糖尿病或雌性小鼠中的疗效至少与正常成年雄性小鼠一样有效[7]。
| Cell experiment [1]: | |
Cell lines | Cardiac fibroblasts(CFs) |
Preparation Method | Tissue culture plastic was used as the experimental platform. Adult CFs were cultured in DMEM containing 10% FBS, 100U/mL penicillin, and 100μg/mL streptomycin with media changed every other day. When nearly confluence, CFs were trypsinized and sub-cultured at 1:3 ratio. CFs were serum-starved for 24h before TGF-β1 treatment (10ng/ml) with or without different concentrations of belumosudil mesylate (0.625, 1.25, 2.5 and 5μM) for 24h. Proteins were extracted for western blot analysis. |
Reaction Conditions | 0.625, 1.25, 2.5 and 5μM; 24h |
Applications | Belumosudil mesylate selectively inhibits ROCK2 and reduces the phosphorylation of Smad2 in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Young adult (C57BL/6, 2–3 months old, male 22–30g, female 16–23g), aged (C57BL/6, 12 months old, 33–52g), or type 2 diabetic mice (db/db, B6.BKS(D)-Lepr db/J, Jackson Laboratory; 2–3 months old, male, 33–50g) |
Preparation Method | Animals received 100, 200 or 300mg/kg belumosudil mesylate twice a day for a total of five doses via orogastric gavage. fMCAO was induced in mice under isoflurane anesthesia (2.5% induction, 1.2% maintenance, in 70% N2O/30% O2). At 48h after fMCAO, infarct areas were measured on ten 1 mm-thick 2,3,5-triphenyltetrazolium chloride (TTC)-stained coronal sections, integrated to calculate the infarct volume, and corrected for ischemic edema by subtracting the volume of ipsilateral non-infarcted tissue from the contralateral hemisphere. |
Dosage form | 100, 200 or 300 mg/kg; i.g. |
Applications | Belumosudil mesylate dose-dependently reduces infarct volume after transient middle cerebral artery occlusion. |
References: | |
| Cas No. | 2109704-99-4 | SDF | |
| 别名 | KD025 mesylate; SLx-2119 mesylate | ||
| 分子式 | C27H28N6O5S | 分子量 | 548.61 |
| 溶解度 | DMSO : 12.5 mg/mL (22.78 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) | 储存条件 | 4°C, sealed storage, away from moisture |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8228 mL | 9.1139 mL | 18.2279 mL |
| 5 mM | 0.3646 mL | 1.8228 mL | 3.6456 mL |
| 10 mM | 0.1823 mL | 0.9114 mL | 1.8228 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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1. 首先保证母液是澄清的；
2.
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Quality Control & SDS
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