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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
Inhibitor
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

References

Publications

Cross References

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 comments )
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