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AM-6494 | AM-6494 : Inhibitor of BACE1, BACE2
RATINGS:
Cellular Use: (2 reviews)

In Model Organisms: (2 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
BACE1
  • IC50:0.4 nM
  • IC50:1.2 nM
BACE2
  • IC50:186 nM
  • IC50:19 nM
up to 100 nM

Selectivity

In Vitro Selectivity Assessment
Potency Assay Off-Target:
AM-6494 is 47 fold selective against BACE2; Tested for selectivity against Related Aspartyl Protease ...

Potency
Cellular
In Vitro

BACE1

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acs.jmedchem.9b01034

BACE2

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acs.jmedchem.9b01034

In Vivo Validations

Rat
Dose: 1 mg/Kg
Route of delivery: Intravenous
Plasma half life: 1.5 h
Systemic clearance: 1.3 L/h/Kg
Volume of Distribution at Steady-State: 1.7 L/Kg

DOI Reference: 10.1021/acs.jmedchem.9b01034

Dose: 3 mg/Kg
Route of delivery: Oral
Area Under the Curve:: 2.4 uM/h
Fb : 99.45%
Bioavailability: 48%

DOI Reference: 10.1021/acs.jmedchem.9b01034

Dog
Dose: 1 mg/Kg
Route of delivery: Intravenous
Plasma half life: 2.0 h
Systemic clearance: 0.9 L/h/Kg
Volume of Distribution at Steady-State: 3.2 L/Kg

DOI Reference: 10.1021/acs.jmedchem.9b01034

Dose: 10 mg/Kg
Route of delivery: Oral
Area Under the Curve:: 22 uM/h
Fb : 97.8%
Bioavailability: 100%

DOI Reference: 10.1021/acs.jmedchem.9b01034

Monkey (Cynomolgus)
Dose: 1 mg/Kg
Route of delivery: Intravenous
Plasma half life: 8.3 h
Systemic clearance: 2.1 L/h/Kg
Volume of Distribution at Steady-State: 17 L/Kg

DOI Reference: 10.1021/acs.jmedchem.9b01034

Dose: 3 mg/Kg
Route of delivery: Oral
Systemic clearance: 28%
Area Under the Curve:: 2.3 uM/h
Fb : 93.9%

DOI Reference: 10.1021/acs.jmedchem.9b01034

Chemical Information

Molecular Formula C22H21F2N5O3S
SMILEs C#CCOc1cnc(C(=O)Nc2cc(F)c(F)c([C@@]3(C)N=C(N)S[C@@]4(COC)C[C@H]43)c2)cn1
InChI InChI=1S/C22H21F2N5O3S/c1-4-5-32-17-10-26-15(9-27-17)19(30)28-12-6-13(18(24)14(23)7-12)21(2)16-8-22(16,11-31-3)33-20(25)29-21/h1,6-7,9-10,16H,5,8,11H2,2-3H3,(H2,25,29)(H,28,30)/t16-,21+,22+/m0/s1
Molecular weight 473.13 Da
AlogP 2.7009000000000007
HBond acceptors 8
HBond donors 3
Atoms 54

Vendors

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Expert Reviews

by SERP
(on 5 Mar 2024)
Cellular Use Rating
In Model Organisms
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,...
by SERP
(on 24 May 2024)
Cellular Use Rating
In Model Organisms
(The reviewer did not leave any public comments)
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