AZD7986 (Synonyms: Brensocatib; INS 1007) |
| رقم الكتالوجGC19052 |
AZD7986 (AZD7986) هو مثبط ثنائي ببتيدل ببتيداز 1 (DPP1) عن طريق الفم مع pIC50s 6.85 و 7.6 و 7.7 و 7.8 و 7.8 في الإنسان والفأر والجرذ والكلب والأرانب ، على التوالي.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1802148-05-5
Sample solution is provided at 25 µL, 10mM.
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AZD7986 is a Dipeptidyl peptidase 1 (DPP1) inhibitor with pIC50s of 6.85, 7.6, 7.7, 7.8, and 7.8 in human, mouse, rat, dog and rabbit, respectively.
Results from cell assay show that AZD7986 is a Dipeptidyl peptidase 1 (DPP1) inhibitor with pIC50s of 6.85, 7.6, 7.7, 7.8, and 7.8 in human, mouse, rat, dog and rabbit, respectively. AZD7986 is stable in the propionaldehyde reactivity assay, with a half-life over 50 h. After differentiation in the presence of AZD7986 (38 pM to 10 uM), concentration-dependent decreases in cell lysate enzyme activity are observed for DPP1, as well as for all of the three NSPs, NE, Pr3, and CatG. AZD7986 inhibits activation of all three NSPs in a concentration dependent manner, with pIC50 values of around 7 for all three NSPs. The reduction of the activities is almost complete, with NE, Pr3, and CatG activities reduced to 4 to 10% of control at 10 uM AZD7986[1].
AZD7986 shows good stability in plasma, with a half life of >10 h. AZD7986 inhibits activation of NE and Pr3, but not CatG, in bone marrow cell lysates in a dose dependent manner in vivo[1].
References:
[1]. Doyle K, et al. Discovery of Second Generation Reversible Covalent DPP1 Inhibitors Leading to an Oxazepane Amidoacetonitrile Based Clinical Candidate (AZD7986). J Med Chem. 2016 Oct 27;59(20):9457-9472.
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Kinase experiment: |
Activation of neutrophil serine proteases (NSPs) 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[1]. |
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Cell experiment: |
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 5×105 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[1]. |
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Animal experiment: |
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. Attermination, bone marrow is taken by femural aspiration for neutrophil serine proteases (NSPs) activity analysis using commercial synthetic peptide substrates[1]. |
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References: [1]. Doyle K, et al. Discovery of Second Generation Reversible Covalent DPP1 Inhibitors Leading to an Oxazepane Amidoacetonitrile Based Clinical Candidate (AZD7986). J Med Chem. 2016 Oct 27;59(20):9457-9472. |
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| Cas No. | 1802148-05-5 | SDF | |
| المرادفات | Brensocatib; INS 1007 | ||
| Canonical SMILES | O=C([C@H]1OCCCNC1)N[C@H](C#N)CC2=CC=C(C3=CC=C(OC(N4C)=O)C4=C3)C=C2 | ||
| Formula | C23H24N4O4 | M.Wt | 420.46 |
| الذوبان | DMSO : ≥ 100 mg/mL (237.83 mM);Water : < 0.1 mg/mL (insoluble) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3783 mL | 11.8917 mL | 23.7835 mL |
| 5 mM | 0.4757 mL | 2.3783 mL | 4.7567 mL |
| 10 mM | 0.2378 mL | 1.1892 mL | 2.3783 mL |
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Quality Control & SDS
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- Purity: >99.50%
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- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 37 reference(s) in Google Scholar.)
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