| 名稱 | LMPTP INHIBITOR 1 hydrochloride |
| 描述 | LMPTP INHIBITOR 1 hydrochloride is a selective inhibitor of low molecular weight protein tyrosine phosphatase ( LMPTP ), with an IC 50 of 0.8 μM for LMPTP-A. |
| 細胞實驗 | Human HepG2 cells are cultured in Eagle's Minimal Essential Medium (ATCC) containing 10% fetal bovine serum (FBS), 100 U/mL penicillin and 100 μg/mL streptomycin. The absence of Mycoplasma contamination in HepG2 cultures is confirmed using the Lonza MycoAlert Mycoplasma Detection Kit. Cells are treated with 10 μM LMPTP inhibitor 1 in serum-starvation media (0.1% FBS) overnight, following which cells are stimulated with 10 nM bovine insulin for 5 min at 37°C. For detection of IR tyrosine phosphorylation by immunoprecipitation/Western blotting, cells are lysed in radioimmunoprecipitation assay buffer containing 1 mM phenylmethylsulfonyl fluoride, 10 μg/mL aprotinin/leupeptin, 10 mM sodium orthovanadate, 5 mM sodium fluoride, and 2 mM sodium pyrophosphate, and the IR is immunoprecipitated using the anti-IRβ Ab. IR tyrosine phosphorylation of immunoprecipitates is determined by Western blotting with the anti-pIR/pIGFR-Y1162/Y1163 Ab [1]. |
| 激酶實驗 | Phosphatase assays are performed in buffer containing 50 mM Bis-Tris, pH 6.0, 1 mM DTT and 0.01% Triton X-100 at 37°C. For assays conducted with 3-O-methylfluorescein phosphate (OMFP) as substrate, fluorescence is monitored continuously at λex = 485 and λem = 525 nm. For assays conducted with para-nitrophenyl phosphate (pNPP) as substrate, the reaction is stopped by addition of 2X reaction volume of 1 M NaOH, and absorbance is measured at 405 nm. IC50 values are determined from plots of LMPTP inhibitor 1 concentration versus percentage of enzyme activity. For inhibitor selectivity assays, each PTP is incubated with either 0.4 mM OMFP or 5 mM pNPP in the presence of 40 μM LMPTP inhibitor 1 or DMSO. Equal units of enzyme activity, comparable to the activity of 10 nM human LMPTP-A, are used. For the inhibitor reversibility assay, 50 nM human LMPTP-A is pre-incubated with 10 μM LMPTP inhibitor 1 or DMSO for 5 min. The enzyme is diluted 100X in phosphatase assay buffer containing 0.4 mM OMFP and fluorescence is measured at the indicated time points [1]. |
| 動物實驗 | LMPTP inhibitor 1 is administered to male B6 or Acp1fl/fl albumin-Cre+ DIO mice at 0.05% w/w in high-fat diet (HFD) rodent chow. Control groups consist of male B6 or Acp1fl/fl albumin-Cre+ littermate mice administered HFD rodent chow alone. Mice are allowed food and water ad libitum and weighed daily. Randomization is not used in these experiments; rather littermate mice are assigned to treatment or control groups in a manner to maintain similar mean body weights between the 2 groups at the start of the study. Insulin-induced liver IR phosphorylation, IPGTT, and fasting insulin levels are assessed after treatment. Diabetic (displaying overnight [13 hr] fasting blood glucose levels ≥140 mg/dL) B6 DIO mice are used in experiments to assess IPGTT and fasting insulin levels [1]. |
| 體外活性 | LMPTP INHIBITOR 1 (hydrochloride) 是一種對低分子量蛋白質(zhì)酪氨酸磷酸酶具有選擇性抑制作用的抑制劑，對LMPTP-A的IC 50值為0.8 μM。LMPTP INHIBITOR 1 對LMPTP-A的抑制效果較之于LMPTP-B更為強大。LMPTP抑制劑1還在人類HepG2肝細胞中，通過胰島素刺激后增強了HepG2 IR的磷酸化[1]。 |
| 體內(nèi)活性 | LMPTP inhibitor 1 具有口服生物可用性，0.03% w/w 的處理約產(chǎn)生 680 nM 的平均血清濃度，而0.05% w/w 的處理則產(chǎn)生 >3 μM；該物質(zhì)還能逆轉(zhuǎn)肥胖小鼠的糖尿病。LMPTP inhibitor 1（0.05% w/w）抑制 LMPTP 活性，顯著改善糖尿病 DIO 小鼠的葡萄糖耐受性并降低空腹胰島素水平，但不影響體重[1]。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 9 mg/mL (18.71 mM)
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| 關(guān)鍵字 | LMPTP INHIBITOR 1 Hydrochloride | LMPTP INHIBITOR 1 hydrochloride |
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| 相關(guān)庫 | 抑制劑庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | 磷酸酶抑制劑化合物庫 | 代謝化合物庫 | NO PAINS 化合物庫 | 糖代謝化合物庫 |