AEP-IN-3 | AEP-IN-3 : Inhibitor of LGMN
RATINGS:
Cellular Use: (2 reviews)

In Model Organisms: (1 reviews)
Vendors

Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
LGMN
  • IC50:7.8 ± 0.9 nM
  • EC50:126 ± 48 nM
  • EC50:75 nM
Inhibitor
1 µM
up to 5 μM

Selectivity

In Vitro Selectivity Assessment
Potency Assay Off-Target:
CEREP protease screen @ 10 uM, with clone to no inhibition of Caspase 3 and Cathepsin S.
Selectivity Assessment Description:
radiometric-based biochemical counter screen panel assay against other proteases/peptidases
In Vitro Selectivity Assessment
Potency Assay Off-Target:
hERG inhibition assay
Selectivity Assessment Description:
No hERG inhibition
In Vitro Selectivity Assessment
Potency Assay Off-Target:
GSH adduct formation
Selectivity Assessment Description:
No flag

Potency
Cellular
In Vitro

LGMN

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acs.jmedchem.3c01804

In Vivo Validations

Mouse
Dose: 1 mg/kg
Route of delivery: Intravenous
Plasma half life: 0.94 hr
Systemic clearance: 10.8 mL/min/kg
Fb : 19%
Volume of Distribution at Steady-State: 0.73 L/kg

DOI Reference: 10.1021/acs.jmedchem.3c01804

Dose: 20 mg/kg
Route of delivery: Oral
Bioavailability: 83%

DOI Reference: 10.1021/acs.jmedchem.3c01804

Negative Control Compounds

canSAR7067859
Notes: AEP-6C is 1.127 uM,144 fold less potent compared to AEP-18 (7.8 nM) in recombinant protein assay J. Med. Chem. 2023, 66, 24, 17026–17043 https://doi.org/10.1021/acs.jmedchem.3c01804

Chemical Information

Molecular Formula C21H21F4N3O4
InChI InChI=1S/C21H21F4N3O4/c1-2-14(10-17(26)29)27-18(30)16-9-13(22)11-28(16)19(31)20(7-8-20)12-3-5-15(6-4-12)32-21(23,24)25/h1,3-6,13-14,16H,7-11H2,(H2,26,29)(H,27,30)/t13-,14-,16+/m1/s1
Molecular weight 455.15 Da
AlogP 0.0
HBond acceptors 7
HBond donors 3
Atoms 53

Expert Reviews


(on 8 Apr 2025 )
Cellular Use Rating
In Model Organisms
AEP-IN-3 is a potent orthosteric inhibitor of Asparagine endopeptidase (AEP). The primary reference describes the structure activity relationship and is disclosing orthogonal structural analogs from the...
(on 7 May 2025 )
Cellular Use Rating
This concentration seems a little high for a ~ 200 nM covalent inhibitor that hasn't been profiled in selectivity assays (e.g. by ABPP). Therefore up to 1 µM would be a safer concentration range.
Note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars. Read more about our evaluation criteria