Antibodies
AZD3839
- 貨號 Cat. No.
- S7118
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
AZD3839
Catalog No.S7118
AZD3839 is a potent and selective inhibitor of human BACE1 with Ki of 26.1 nM.
| Availability |
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Biological Activity
| Description | AZD3839 is a potent and selective inhibitor of human BACE1 with Ki of 26.1 nM. | |||||
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| Targets | BACE1 | |||||
| IC50 | 26.1 nM (Ki) [1] | |||||
| In vitro | AZD3839 is soaked into crystals of BACE1. AZD3839 binds to BACE1 in a flap-open conformation with the pyridine nitrogen located close to the S2 pocket, interacting with Trp-76 via an important hydrogen bond. In a concentration-dependent manner, AZD3839 inhibited BACE1 activity in a biochemical fluorescence resonance energy transfer (FRET) assay, Aβ and sAPPβ release from modified and wild-type human SH-SY5Y cells and mouse N2A cells as well as from mouse and guinea pig primary cortical neurons. Selectivity against BACE2 and cathepsin D is 14 and >1000-fold, respectively. [1] | |||||
| In vivo | In C57BL/6 mice, orally administrated AZD3839 gave a dose- and time-dependent reduction of plasma and brain Aβ. AZD3839 exhibits dose- and time-dependent lowering of plasma, brain, and cerebrospinal fluid Aβ levels in mouse, guinea pig, and non-human primate. Pharmacokinetic/pharmacodynamic analyses of mouse and guinea pig data shows a good correlation between the potency of AZD3839 in primary cortical neurons and in vivo brain effects. These results suggest that AZD3839 effectively reduces the levels of Aβ in brain, CSF, and plasma in several preclinical species. [1] | |||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay: [1]
| hBACE1 and hBACE2 Time-resolved-FRET Assay | The soluble part of the human β-secretase (recombinant hBACE1 enzyme, amino acids 1–460, or hBACE2 enzyme, amino acids 1–473) is mixed with compound in reaction buffer (sodium acetate, CHAPS, Triton X-100, EDTA, pH 4.5) and preincubated for 10 min. Substrate (Europium)CEVNLDAEFK(Qsy7) is added, and the reaction is allowed to proceed for 6.5 h in darkness under the lid at 22 °C until stopped with the addition of sodium acetate, pH 9. The fluorescence of the product is measured on a Victor II 1420 Multilabel Counter plate reader with an excitation wavelength of 340 nm and an emission wavelength of 615 nm. |
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Animal Study: [1]
| Animal Models | C57BL/6 mice |
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| Dosages | 80 and 160 μmol/kg (35 and 69 mg/kg) |
| Administration | oral |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01348737 | Completed | Alzheimer’s Disease|Safety|Tolerability|Blood Concentration|Healthy Volunteers | AstraZeneca | 2011-06 | Phase 1 |
Chemical Information
| Molecular Weight (MW) | 449.4 |
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| Formula | C24H15F4N5 |
| CAS No. | 1227163-56-5 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Chemical Name | 1H-Isoindol-3-amine, 4-fluoro-1-[3-(5-pyrimidinyl)phenyl]-1-[2-(trifluoromethyl)-4-pyridinyl]- |
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