Home Neuronal Signaling BACE inhibitor Lanabecestat (AZD3293)

research use only

Lanabecestat (AZD3293) BACE inhibitor

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

Lanabecestat (AZD3293) BACE inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 412.53

Purity & Quality Control

Related Products

Signaling Pathway

BACE Signaling Pathways

BACE Signaling Pathway

Mechanism of Action

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 this compound with respect to secretion of Aβ40 and sAβPPβ is studied in a range of cellular models, it 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). It 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. 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

After incubation with different concentrations of Lanabecestat (AZD3293) for 5 to 16 h, 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 studies in mice, guinea pigs, and dogs demonstrated that Lanabecestat (AZD3293) produces significant dose- and time-dependent reductions in plasma, cerebrospinal fluid, and brain concentrations of Aβ40, Aβ42, and sAβPPβ. In the dog PK study, its bioavailability was determined to be 80% (F = 0.8). The preclinical data strongly support the clinical development of this compound, and patients with AD are currently being recruited into a combined Phase 2/3 study to test its disease-modifying properties[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

References
  • https://pubmed.ncbi.nlm.nih.gov/26890753/

Chemical Information

Molecular Weight 412.53 Formula

C26H28N4O
CAS No. 1383982-64-6 SDF Download SDF
Synonyms LY3314814
Smiles CC#CC1=CC(=CN=C1)C2=CC3=C(CC4(C35N=C(C(=N5)N)C)CCC(CC4)OC)C=C2

Storage and Stability

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


Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.


In vivo Formulation Calculator

Preparing Stock Solutions

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

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

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.