AM-6494

AM-6494 : Inhibitor of BACE1, BACE2

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(2 ratings)

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Probe AM-6494 is in the process of SERP review.

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Information

BACE1
BACE2

Inhibitor

up to 100 nM

Probe Availability:

In Vitro Validations

Uniprot ID: P56817

Target Class: Enzyme

Target SubClass: Peptidase

Potency: IC50

Potency Value: 0.4 nM

Potency Assay: Enzymatic assay

PDB ID for probe-target interaction (3D structure): 6PZ4

Target aliases:

Beta-secretase 1, KIAA1149, BACE, BACE1, BACE1_HUM ...

DOI Reference: 10.1021/acs.jmedchem.9b01034

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): AM-6494 is 47 fold selective against BACE2; Tested for selectivity against Related Aspartyl Proteases: CatD 137 nM, CatE 1377 nM, pepsin 686 nM, renin 678 nM

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

AM-6494 is a highly potent and orally bioavailable BACE1 inhibitor (IC50: 0.4 nM) with selectivity over BACE2 (IC50: 18.6 nM) and much higher selectivity over other aspartic proteases (Cathepsins D, E, Pepsin, Renin). However, users should note that no data is available on the activity of AM-6494 on other proteases and non-protease targets. Cross-species target activity has been confirmed in rat, mouse, dog and monkey assays with similar IC50 to the human enzyme and in vivo pharmacokinetic data is available in rat, dog and monkey (cynomolgus) indicating good utility in these model organisms. Other small molecule inhibitors with selectivity for BACE1 over BACE2 are available (PF-06751979 and BACE 1-In-4), however AM-6494 appears to be the most potent molecule against BACE1 with detailed in vivo pharmacokinetic profiles across rat, dog and monkey supporting its use in cell and in vivo models.

(last updated: 5 Mar 2024 )

SERP Ratings

In Cell Rating

In Model Organisms

(last updated: 24 May 2024 )