Home Neuronal Signaling BACE inhibitor Lanabecestat (AZD3293) For research use only.

Lanabecestat (AZD3293)

Synonyms: LY3314814

Lanabecestat (AZD3293, LY3314814) is an oral beta-secretase 1 cleaving enzyme (BACE) inhibitor with an inhibitory constant Ki  of 0.4 nM.

Lanabecestat (AZD3293) Chemical Structure

Lanabecestat (AZD3293) Chemical Structure

CAS No. 1383982-64-6

Purity & Quality Control

Lanabecestat (AZD3293) Related Products

Signaling Pathway

BACE Signaling Pathways

BACE Signaling Pathway

Biological Activity

Description Lanabecestat (AZD3293, LY3314814) is an oral beta-secretase 1 cleaving enzyme (BACE) inhibitor with an inhibitory constant Ki  of 0.4 nM.
Targets
BACE [1]
(Cell-free assay)
0.4 nM(Ki)
In vitro
In vitro Lanabecestat（AZD3293, LY3314814）is a potent, highly permeable, orally active, blood-brain barrier (BBB) penetrating, BACE1 inhibitor with unique slow off-rate kinetics. When the potency of AZD3293 with respect to secretion of Aβ40 and sAβPPβ is studied in a range of cellular models, the compound displays pM potency in primary neuron cultures from mice and guinea pigs and in SH-SY5Y cells over-expressing AβPP (IC50 = 610 pM, 310 pM, and 80 pM, respectively). AZD3293 is also tested in a panel of more than 350 in vitro radioligand binding and enzyme activity assays, covering a diverse range of receptors, ion channels, transporters, kinases, and enzymes, up to a concentration of 10μM of AZD3293. A few significant responses are observed, but these had at least a 1,000-fold selectivity against BACE1, thus indicating specificity to BACE1. The off-rate of AZD3293 has an estimated t1/2 of approximately 9 h[1].
Cell Research Cell lines SH-SY5Y, SH-SY5Y overexpressing wild type AβPP, HEK293 cells overexpressing AβPP with the Swedish mutation (K595N/M596L), N2A cells, and primary cortical neurons isolated from fetal C57BL/6 mice (E16) or Dunkin-Hartley guinea pigs (E25-27)
Concentrations --
Incubation Time 5 to 16 h
Method

The cells are incubated with different AZD3293 concentrations for 5 to 16 h, and the release of sAβPPβ, Aβ1-40, Aβ1-42, or sAβPPα into the medium is analyzed using specific commercial ELISA or kits from Meso Scale Discovery.
In Vivo
In vivo In vivo in mice, guinea pigs, and dogs, AZD3293 displays significant dose- and time-dependent reductions in plasma, cerebrospinal fluid, and brain concentrations of Aβ40, Aβ42, and sAβPPβ. In the dog PK study, the bioavailability of AZD3293 is determined to be 80% (F = 0.8). The preclinical data strongly support the clinical development of AZD3293, and patients with AD are currently being recruited into a combined Phase 2/3 study to test the disease-modifying properties of AZD3293[1].
Animal Research Animal Models C57BL/6 mice
Dosages 50, 100, or 200μmol/kg
Administration oral administration
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03499041 Withdrawn
Hepatic Impairment
Eli Lilly and Company|AstraZeneca
 June 2018 Phase 1
NCT03222427 Completed
Healthy
AstraZeneca|Eli Lilly and Company
 January 15 2018 Phase 1
NCT03019549 Completed
Healthy
AstraZeneca|Eli Lilly and Company
 January 12 2017 Phase 1
NCT02663128 Completed
Healthy
AstraZeneca|Eli Lilly and Company
 January 31 2016 Phase 1

Chemical Information & Solubility

Molecular Weight 412.53 Formula

C26H28N4O
CAS No. 1383982-64-6 SDF Download Lanabecestat (AZD3293) SDF
Smiles CC#CC1=CC(=CN=C1)C2=CC3=C(CC4(C35N=C(C(=N5)N)C)CCC(CC4)OC)C=C2
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 82 mg/mL ( (198.77 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 82 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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