JTT 551
目录号 : GC31499
JTT551是一种选择性的蛋白酪氨酸磷酸酶1B(PTP1B)抑制剂，Ki值为0.22μM，同时对T细胞蛋白酪氨酸磷酸酶(TCPTP）也有作用，Ki值为9.3μM，可用于二型糖尿病的研究。
Cas No.:776309-04-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Mice[1]Db/db mice are used in the assay. JTT 551 at doses of 3 or 30 mg/kg or pioglitazone at 3 mg/kg is administered orally to 6-week-old male db/db mice (n = 5) once daily for 4 weeks. Body weight is measured twice weekly and blood samples are collected from the orbital venous plexus before dosing on Days 7, 14 and 28. Blood glucose, insulin, triglyceride (TG) and total cholesterol (TC) levels are determined at the respective blood-sampling time points, and the haemoglobin A1c (HbA1c) level is determined before dosing on Day 28. HbA1c level is measured[1]. |
References: [1]. Fukuda S, et al. Pharmacological profiles of a novel protein tyrosine phosphatase 1B inhibitor, JTT-551. Diabetes Obes Metab. 2010 Apr;12(4):299-306. | |
JTT 551 is selective a protein tyrosine phosphatase 1B (PTP1B) inhibitor, with Kis of 0.22 μM and 9.3 μM for PTP1B and TCPTP (T-cell protein tyrosine phosphatase), respectively; JTT 551 can be used in the research of type 2 diabetes mellitus.
JTT 551 is selective a protein tyrosine phosphatase 1B (PTP1B) inhibitor, with Kis of 0.22 μM and 9.3 μM for PTP1B and TCPTP (T-cell protein tyrosine phosphatase), respectively. JTT 551 shows low affinity at CD45 PTP (CD45) and leucocyte common antigen-related (LAR) PTP with Kis of both >30 μM. Furthermore, JTT-551 (10 and 30 μM) enhances the insulin-induced deoxyglucose uptake in a dosedependent manner[1].
JTT 551 (3 mg/kg, 30 mg/kg, p.o.) dose-dependently decreases blood glucose level on Days 7, 14 and 28 in db/db Mice. JTT 551 also significantly reduces triglyceride (TG) level at 30 mg/kg on Day 7 but does not alter insulin and total cholesterol (TC) levels[1].
[1]. Fukuda S, et al. Pharmacological profiles of a novel protein tyrosine phosphatase 1B inhibitor, JTT-551. Diabetes Obes Metab. 2010 Apr;12(4):299-306.
| Cas No. | 776309-04-7 | SDF | |
| Canonical SMILES | O=C(O)CN(CC1=NC=C(C(C)(C)C)S1)CC2=NC(C3=CC=C(COC4=CC=C(C(CCC)CCC)C=C4)C=C3)=CS2 | ||
| 分子式 | C34H43N3O3S2 | 分子量 | 605.85 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| 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 | 1.6506 mL | 8.2529 mL | 16.5057 mL |
| 5 mM | 0.3301 mL | 1.6506 mL | 3.3011 mL |
| 10 mM | 0.1651 mL | 0.8253 mL | 1.6506 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Pharmacological effects of JTT-551, a novel protein tyrosine phosphatase 1B inhibitor, in diet-induced obesity mice
Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of leptin signaling as well as insulin signaling. JTT-551 is a new PTP1B inhibitor, which is reported to improve glucose metabolism by enhancement of insulin signaling. We have evaluated an antiobesity effect of JTT-551 using diet-induced obesity (DIO) mice. A single administration of JTT-551 was provided to DIO mice with or without leptin, and DIO mice were given food containing JTT-551 for six weeks. A single administration of JTT-551 with leptin treatment enhanced the food inhibition and the signal transducer and activator of transcription 3 (STAT3) phosphorylation in hypothalamus. Moreover, chronic administration of JTT-551 showed an antiobesity effect and an improvement of glucose and lipid metabolism in DIO mice. JTT-551 shows an antiobesity effect possibly by enhancement of leptin signaling and could be useful in the treatment of type 2 diabetes and obesity.
Pharmacological profiles of a novel protein tyrosine phosphatase 1B inhibitor, JTT-551
Aim: Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin signalling, is a novel therapeutic target for type 2 diabetes mellitus. We evaluated in vitro and in vivo the pharmacological profiles of a new PTP1B inhibitor, JTT-551: monosodium ({[5-(1,1-dimethylethyl)thiazol-2-yl]methyl} {[(4-{4-[4-(1-propylbutyl)phenoxy]methyl}phenyl)thiazol-2-yl]methyl}amino)acetate.
Methods: PTP1B inhibitory activity and the inhibition mode were assayed with p-nitrophenyl phosphate as a substrate, and the selectivity of JTT-551 against other PTPs, including T-cell protein tyrosine phosphatase (TCPTP), CD45 protein tyrosine phosphatase (CD45) and leucocyte common antigen-related protein tyrosine phosphatase (LAR), was evaluated. Glucose uptake with JTT-551 treatment was evaluated in L6 rat skeletal myoblasts (L6 cells). In the in vivo study, we investigated the effects on insulin receptor (IR) phosphorylation and blood chemical parameters with JTT-551 administration in ob/ob mice and db/db mice.
Results: JTT-551 showed an inhibitory effect on PTP1B with a Ki value of 0.22 microM, and a mixed-type inhibition mode. Ki values of TCPTP, CD45 and LAR were 9.3, 30 or higher and 30 or higher microM, respectively, and JTT-551 exhibited clear selectivity against the other PTPs. Moreover, JTT-551 increased the insulin-stimulated glucose uptake in L6 cells. A single administration of JTT-551 in ob/ob mice enhanced the IR phosphorylation of liver and reduced the glucose level. In db/db mice, chronic administration showed a hypoglycaemic effect without an acceleration of body weight gain.
Conclusions: JTT-551, a newly developed PTP1B inhibitor, improves glucose metabolism by enhancement of insulin signalling and could be useful in the treatment of type 2 diabetes mellitus.
Recent updates on development of protein-tyrosine phosphatase 1B inhibitors for treatment of diabetes, obesity and related disorders
The aim of this review was to discuss an overview of type 2 diabetes; biology of PTP1B; role of PTP1B in metabolic disorders; and recent updates in the development of PTP1B inhibitors reported in literature since 1994. In this study, extensive literature search was carried out on PTP1B inhibitors of natural as well as synthetic origin in various scientific databases and research articles related to discovery of PTP1B inhibitors were selected for this study. Protein tyrosine phosphatase 1B (PTP1B) is an important therapeutic target for several human diseases including type 2 diabetes, obesity and cancer because of its seminal part as a negative modulator in both insulin and leptin signaling pathways. A large number of molecules of broad chemical diversity were reported as potent and selective PTP1B inhibitors over other protein tyrosine phosphatases. Several of these molecules have shown their potential in the treatment of various human diseases including type 2 diabetes, obesity, inflammation and cancer in various animal models. But only a very limited number of PTP1B inhibitors (including ertiprotafib, trodusquemine and JTT-551) has entered clinical trials and are finally withdrawn owing to their unsatisfactory effectiveness and undesirable adverse effects. Consequently, it is still highly imperative and of great importance to develop potent, highly selective and safe PTP1B inhibitors.
Status of research on natural protein tyrosine phosphatase 1B inhibitors as potential antidiabetic agents: Update
Protein tyrosine phosphatase 1B (PTP1B) is a crucial therapeutic target for multiple human diseases comprising type 2 diabetes (T2DM) and obesity because it is a seminal part of a negative regulator in both insulin and leptin signaling pathways. PTP1B inhibitors increase insulin receptor sensitivity and have the ability to cure insulin resistance-related diseases. However, the few PTP1B inhibitors that entered the clinic (Ertiprotafib, ISIS-113715, Trodusquemine, and JTT-551) were discontinued due to side effects or low selectivity. Molecules with broad chemical diversity extracted from natural products have been reported to be potent PTP1B inhibitors with few side effects. This article summarizes the recent PTP1B inhibitors extracted from natural products, clarifying the current research progress, and providing new options for designing new and effective PTP1B inhibitors.