| 名称 | Brensocatib |
| 描述 | Brensocatib (AZD7986) is a Dipeptidyl peptidase 1 (DPP1) inhibitor (pIC50s: 6.85, 7.7, 7.6, 7.8, and 7.8 in human, rat, mouse, rabbit, and dog, respectively). |
| 细胞实验 | Cellular potency is studied using the DPP1-expressing monocytic U937 cell line. Briefly, cells grown in RPMI are plated on 384-well polypropylene v-bottom plates at a density of 5×10^5 cells/mL per well. Added to this is 10 μL of AZD7986 at 37°C for 60 min, followed by 350 μM Gly-Phe-AFC. The well fluorescence is read using a multilabel plate reader. Data are analyzed to calculate pIC50 values. |
| 激酶实验 | Activation of neutrophil serine proteases is assessed in vitro using primary bone marrow-derived CD34+ neutrophil progenitor cells. Cells are cultured in media supplemented with rhSCF and rhIL-3 for 7 days, and then for a further 7 days in the presence of G-CSF and different concentrations of AZD7986 (38 pM to 10 μM). After harvesting and lysis with 10% Triton X-100 buffer, cell lysates are kept at -20°C until NSP activity analysis. |
| 动物实验 | Rats are used for the in vivo study. Naive rats are dosed orally twice daily with AZD7986 at 0.2, 2, and 20 mg/kg/day for 8 days. At termination, bone marrow is taken by femural aspiration for neutrophil serine proteases activity analysis using commercial synthetic peptide substrates. |
| 体外活性 | AZD7986在丙醛活性测定中表现稳定，半衰期超过50小时。经AZD7986（38 pM至10 μM）处理后，观察到DPP1及所有三种NSPs（NE、Pr3、CatG）的细胞裂解物酶活性呈浓度依赖性下降。AZD7986以浓度依赖性方式抑制所有三种NSPs的激活，三者的pIC50值均约为7。这种活性降低几乎是完全的，NE、Pr3和CatG的活性在10 μM AZD7986下降至对照的4至10%。 |
| 体内活性 | AZD7986在血浆中显示出良好的稳定性，半衰期超过10小时。在体内，AZD7986以剂量依赖的方式抑制了骨髓细胞裂解物中的Pr3和NE的激活，但不抑制CatG的激活。 |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | 0.5% HPMC and 0.1% Tween 80 in 0.1 M citrate buffer (pH=3) : 1 mg/mL (2.38 mM), Suspension
DMSO : ≥100 mg/mL (237.83 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (4.76 mM), Sonication is recommended.
H2O : Insoluble
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| 关键字 | INS-1007 | INS1007 | Inhibitor | inhibit | DPP1 | DPP | Dipeptidyl peptidase 1 (DPP1) | Dipeptidyl peptidase 1 | Dipeptidyl Peptidase | Brensocatib | AZD-7986 | AZD 7986 |
| 相关产品 | Teneligliptin hydrobromide | MG-132 | Sitagliptin phosphate | 10-Undecenoic acid | Sitagliptin | Anagliptin | Alloxan monohydrate | 10-Undecenoic acid zinc salt | Sitagliptin phosphate monohydrate | 4'-Hydroxychalcone | Vildagliptin | Tripterin |
| 相关库 | 抑制剂库 | 经典已知活性库 | 已知活性化合物库 | ReFRAME 相关化合物库 | 上市药物库 | 蛋白酶抑制剂库 | NO PAINS 化合物库 | FDA 上市药物库 | 血液病分子库 | 临床期小分子药物库 | 药物功能重定位化合物库 | 共价抑制剂库 |