PTP1B Inhibitor
(Synonyms: 3-(3,5-二溴-4-羟基苯甲酰基)-2-乙基-N-[4-[(2-噻唑氨基)磺酰基]苯基]-6-苯并呋喃磺酰胺) 目录号 : GC44775A cell-permeable allosteric inhibitor of PTP1B
Cas No.:765317-72-4
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
- Datasheet
Protein tyrosine phosphatase 1B (PTP1B) has critical roles in cell signaling relevant to diabetes, obesity, and cancer. PTP1B inhibitor is a cell-permeable allosteric inhibitor of PTP1B (IC50s = 4 and 8 µM for 403 and 298 residue PTP1B forms, respectively). It binds reversibly and non-competitively, altering the conformation of the catalytic pocket. PTP1B inhibitor selectively increases the phosphorylation of the insulin receptor, insulin receptor substrate 1, and Akt, mimicking the action of insulin.
| Cas No. | 765317-72-4 | SDF | |
| 别名 | 3-(3,5-二溴-4-羟基苯甲酰基)-2-乙基-N-[4-[(2-噻唑氨基)磺酰基]苯基]-6-苯并呋喃磺酰胺 | ||
| Canonical SMILES | O=S(NC1=CC=C(S(NC2=NC=CS2)(=O)=O)C=C1)(C3=CC=C(C(C(C4=CC(Br)=C(O)C(Br)=C4)=O)=C(CC)O5)C5=C3)=O | ||
| 分子式 | C26H19Br2N3O7S3 | 分子量 | 741.5 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS(pH7.2) (1:1): 0.5 mg/ml,Ethanol: 10 mg/ml | 储存条件 | Store at -20°C, protect from light |
| 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 | 1.3486 mL | 6.7431 mL | 13.4862 mL |
| 5 mM | 0.2697 mL | 1.3486 mL | 2.6972 mL |
| 10 mM | 0.1349 mL | 0.6743 mL | 1.3486 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。
PTP1B Inhibitor alleviates deleterious microglial activation and neuronal injury after ischemic stroke by modulating the ER stress-autophagy axis via PERK signaling in microglia
Aging (Albany NY) 2021 Jan 20;13(3):3405-3427.PMID:33495405DOI:10.18632/aging.202272.
Cerebral ischemia/reperfusion (IR) after ischemic stroke causes deleterious microglial activation. Protein tyrosine phosphatase 1B (PTP1B) exacerbates neuroinflammation, yet the effect of the inhibition on microglial activation and cerebral IR injury is unknown. A cerebral IR rat model was induced by middle cerebral artery occlusion (MCAO) and reperfusion. The PTP1B Inhibitor, sc-222227, was administered intracerebroventricularly. Neurologic deficits, infarct volume, and brain water content were examined. An in vitro oxygen glucose deprivation/reoxygenation (OGD/R) model was established in primary microglia and BV-2 cells. Microglial activation/polarization, endoplasmic reticulum (ER) stress, autophagy, and apoptosis were detected using western blot, immunohistology, ELISA, and real-time PCR. Protein interaction was assessed by a proximity ligation assay. The results showed a significant increase in microglial PTP1B expression after IR injury. Sc-222227 attenuated IR-induced microglial activation, ER stress, and autophagy and promoted M2 polarization. Upon OGD/R, sc-222227 mitigated microglial activation by inhibiting ER stress-dependent autophagy, the effect of which was abolished by PERK activation, and PERK inhibition attenuated microglial activation. The PTP1B-phosphorylated PERK protein interaction was significantly increased after OGD/R, but decreased upon sc-222227 treatment. Finally, sc-222227 mitigated neuronal damage and neurologic deficits after IR injury. Treatment targeting microglial PTP1B might be a potential therapeutic strategy for ischemic stroke treatment.
PTP1B as a drug target: recent developments in PTP1B Inhibitor discovery
Drug Discov Today 2007 May;12(9-10):373-81.PMID:17467573DOI:10.1016/j.drudis.2007.03.011.
Protein tyrosine phosphatase 1B (PTP1B) is an effective target for the treatment of both type 2 diabetes and obesity; however, targeting PTP1B for drug discovery is challenging because of the highly conserved and positively charged active-site pocket. Tremendous progress has been made in the development of potent and selective PTP1B inhibitors that engage both the active site and no catalytic sites. Several strategies are being pursued to improve the pharmacological properties of PTP1B inhibitors. These new developments suggest that it is feasible to acquire PTP1B-based, small-molecule therapeutics with the requisite potency and selectivity. Future efforts will probably transform the potent and selective PTP1B inhibitors into orally available drugs with desirable physicochemical properties and in vivo efficacies.
PTP1B Inhibitor promotes endothelial cell motility by activating the DOCK180/Rac1 pathway
Sci Rep 2016 Apr 7;6:24111.PMID:27052191DOI:10.1038/srep24111.
Promoting endothelial cell (EC) migration is important not only for therapeutic angiogenesis, but also for accelerating re-endothelialization after vessel injury. Several recent studies have shown that inhibition of protein tyrosine phosphatase 1B (PTP1B) may promote EC migration and angiogenesis by enhancing the vascular endothelial growth factor receptor-2 (VEGFR2) signalling. In the present study, we demonstrated that PTP1B Inhibitor could promote EC adhesion, spreading and migration, which were abolished by the inhibitor of Rac1 but not RhoA GTPase. PTP1B Inhibitor significantly increased phosphorylation of p130Cas, and the interactions among p130Cas, Crk and DOCK180; whereas the phosphorylation levels of focal adhesion kinase, Src, paxillin, or Vav2 were unchanged. Gene silencing of DOCK180, but not Vav2, abrogated the effects of PTP1B Inhibitor on EC motility. The effects of PTP1B Inhibitor on EC motility and p130Cas/DOCK180 activation persisted in the presence of the VEGFR2 antagonist. In conclusion, we suggest that stimulation of the DOCK180 pathway represents an alternative mechanism of PTP1B inhibitor-stimulated EC motility, which does not require concomitant VEGFR2 activation as a prerequisite. Therefore, PTP1B Inhibitor may be a useful therapeutic strategy for promoting EC migration in cardiovascular patients in which the VEGF/VEGFR functions are compromised.
An Isoform-Selective PTP1B Inhibitor Derived from Nitrogen-Atom Augmentation of Radicicol
Biochemistry 2019 Jul 30;58(30):3225-3231.PMID:31298844DOI:10.1021/acs.biochem.9b00499.
A library of natural products and their derivatives was screened for inhibition of protein tyrosine phosphatase (PTP) 1B, which is a validated drug target for the treatment of obesity and type II diabetes. Of those active in the preliminary assay, the most promising was compound 2 containing a novel pyrrolopyrazoloisoquinolone scaffold derived by treating radicicol (1) with hydrazine. This nitrogen-atom augmented radicicol derivative was found to be PTP1B selective relative to other highly homologous nonreceptor PTPs. Biochemical evaluation, molecular docking, and mutagenesis revealed 2 to be an allosteric inhibitor of PTP1B with a submicromolar Ki. Cellular analyses using C2C12 myoblasts indicated that 2 restored insulin signaling and increased glucose uptake.
A Novel PTP1B Inhibitor-Phosphate of Polymannuronic Acid Ameliorates Insulin Resistance by Regulating IRS-1/Akt Signaling
Int J Mol Sci 2021 Nov 24;22(23):12693.PMID:34884501DOI:10.3390/ijms222312693.
Protein tyrosine phosphatase 1B (PTP1B) is a critical negative modulator of insulin signaling and has attracted considerable attention in treating type 2 diabetes mellitus (T2DM). Low-molecular-weight polymannuronic acid phosphate (LPMP) was found to be a selective PTP1B Inhibitor with an IC50 of 1.02 ± 0.17 μM. Cellular glucose consumption was significantly elevated in insulin-resistant HepG2 cells after LPMP treatment. LPMP could alleviate oxidative stress and endoplasmic reticulum stress, which are associated with the development of insulin resistance. Western blot and polymerase chain reaction (PCR) analysis demonstrated that LPMP could enhance insulin sensitivity through the PTP1B/IRS/Akt transduction pathway. Furthermore, animal study confirmed that LPMP could decrease blood glucose, alleviate insulin resistance, and exert hepatoprotective effects in diabetic mice. Taken together, LPMP can effectively inhibit insulin resistance and has high potential as an anti-diabetic drug candidate to be further developed.