NIBR-LTSi
目录号 : GC71472NIBR-LTSi是一种高选择性的LATS激酶抑制剂，IC50为2.16µM。
Sample solution is provided at 25 µL, 10mM.
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NIBR-LTSi is a highly selective, active-site binding LATS kinase inhibitor displayed an IC50 of 2.16µM. Since LATS kinases are direct negative regulators of YAP activity, NIBR-LTSi has good oral bioavailability and favorable pharmacokinetic (PK) profile enable YAP activation in vivo[1].
In vitro, HEK293A cells were treated with 5µM NIBR-LTSi for 24 hours increased YAP nuclear translocation, reduced YAP phosphorylation, and enhanced the expression of YAP target genes (CYR61, CTGF, ANKRD1). NIBR-LTSi treatment also increased cell proliferation[1]. 50µM NIBR-LTSi were included in mouse explant cultures and incubated for 24h. NIBR-LTSi treatment activates YAP in basal epithelial cells and induced wound healing in some mouse explants cultured in air-liquid interface conditions[2]. NIBR-LTSi (2.5μM) was added to the culture medium of periodontal ligament stem cell (PDLSCs) at passage 20 with senolytics for 3 days. The inhibition of senescence-associated P21 by senolytics were significantly reversed. NIBR-LTSi treatment increased the expression level of the anti-apoptotic gene BCL2, whereas decreased the expression level of the pro-apoptotic gene BAX[3].
In vivo, NIBR-LTSi oral administrated (100mg/kg) or intravenously injected (1mg/kg) into C57BL/6 mice inhibited YAP phosphorylation in liver tissue, indicating effective LATS inhibition.Treatment of C57BL/6 WT mice with a single dose of NIBR-LTSi(either 30 or 100mg/kg) by oral gavage immediately after partial hepatectomy and monitored proliferation 30 h later. While vehicle-treated mice only showed few proliferating hepatocytes, NIBR-LTSi significantly induced hepatocyte proliferation in a dose dependent manner[1].
References:
[1] Namoto K, Baader C, Orsini V, et al. NIBR-LTSi is a selective LATS kinase inhibitor activating YAP signaling and expanding tissue stem cells in vitro and in vivo. Cell Stem Cell. 2024 Apr 4;31(4):554-569.e17.
[2] Tsissios G, Leleu M, Hu K, et al. Species-specific oxygen sensing governs the initiation of vertebrate limb regeneration. bioRxiv. 2024 Dec;629359
[3] Jia L L, Xiao H, Hao Z H, et al. Senolytic elimination of senescent cells improved periodontal ligament stem cell-based bone regeneration partially through inhibiting YAP. Biochim Biophys Acta Mol Cell Res. 2025 Mar;1872(3):119921.
NIBR-LTSi是一种高选择性的LATS激酶抑制剂，IC50为2.16µM。由于LATS激酶是YAP活性的直接负调节因子，NIBR-LTSi具有良好的口服生物利用度和药代动力学（PK）特性，可在体内激活YAP[1]。
体外实验中，HEK293A细胞经5µM NIBR-LTSi处理24小时后，YAP核转位增加，YAP磷酸化减少，YAP靶基因（CYR61、CTGF、ANKRD1）表达增强。NIBR-LTSi处理还增加了细胞增殖[1]。在小鼠组织培养中加入50µM NIBR-LTSi，孵育24小时。NIBR-LTSi处理激活了基底上皮细胞中的YAP，并在一些培养于气液界面条件下的小鼠组织中诱导了伤口愈合[2]。向第20代牙周韧带干细胞（PDLSCs）的培养基中加入2.5µM NIBR-LTSi，与抗衰老药物共同培养3天。抗衰老药物对衰老相关P21的抑制作用被显著逆转。NIBR-LTSi处理增加了抗凋亡基因BCL2的表达水平，同时降低了促凋亡基因BAX的表达水平[3]。
体内实验中，通过口服（100mg/kg）或静脉注射（1mg/kg）将NIBR-LTSi给予C57BL/6小鼠，在肝脏组织中抑制了YAP的磷酸化，表明LATS被有效抑制。对C57BL/6野生型小鼠进行部分肝切除术后，立即通过口服给予单剂量NIBR-LTSi（30或100mg/kg），并在30小时后监测增殖情况。与给予载体的小鼠相比，NIBR-LTSi显著以剂量依赖性方式诱导肝细胞增殖[1]。
| Cell experiment [1]: | |
Cell lines | Periodontal ligament stem cell |
Preparation Method | NIBR-LTSi (2.5μM) was added to the culture medium of Periodontal ligament stem cell (PDLSCs) at passage 20. |
Reaction Conditions | 2.5μM; 3 days |
Applications | The inhibition of senescence-associated P21 by senolytics were significantly reversed. NIBR-LTSi treatment increased the expression level of the antiapoptotic gene BCL2, whereas decreased the expression level of the proapoptotic gene BAX. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation Method | Partial hepatectomy (PHx) was performed on mice. Dosing of the mice with NIBR-LTSi (30mg/kg, 100mg/kg) or vehicle was performed directly after PHx. The regenerated liver was harvested 30 hours post-surgery. PHx samples were fixed in 10% (vol/vol) neutral-buffered formalin, paraffin embedded and sectioned. |
Dosage form | 30 or 100mg/kg; oral gavage; a single dose |
Applications | NIBR-LTSi robustly activated YAP signaling and induced hepatocyte proliferation. |
References: | |
| Cas No. | SDF | ||
| 分子式 | C18H20N4O | 分子量 | 308.38 |
| 溶解度 | DMSO : 2 mg/mL (6.49 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 | -20°C |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.2428 mL | 16.2138 mL | 32.4275 mL |
| 5 mM | 0.6486 mL | 3.2428 mL | 6.4855 mL |
| 10 mM | 0.3243 mL | 1.6214 mL | 3.2428 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
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，
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 saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >99.50%
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