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ATABECESTAT | ATABECESTAT : 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
  • IC50:9.8 nM
  • IC50:1.1 nM
BACE2
      Inhibitor
      100 nM (inhibition of both BACE1 and BACE2)

      Selectivity

      In Vitro Selectivity Assessment
      Selectivity Assessment Description:
      Inhibited BACE2 (IC50 = 5.6 nM) with comparable potency as for BACE1, whereas it was extremely selec ...

      Potency
      Cellular
      In Vitro

      BACE1

      Mode of Action: Inhibitor

      Structure-Activity-Relationship data available? No

      DOI Reference: 10.1021/acs.jmedchem.0c01917

      BACE2

      Mode of Action: Inhibitor

      Structure-Activity-Relationship data available? No

      DOI Reference: 10.1021/acs.jmedchem.0c01917

      In Vivo Validations

      Rat
      Dose: 0.3 mg /Kg
      Route of delivery: Intravenous
      Plasma half life: 5.52 h
      Systemic clearance: 22.8 mL/min/Kg
      Volume of Distribution at Steady-State: 4.46 L/Kg

      DOI Reference: 10.1021/acs.jmedchem.0c01917

      Dose: 1 mg/Kg
      Route of delivery: Oral
      Cmax: 73.9 ng/mL
      Area Under the Curve:: 386 ng*h/mL
      Bioavailability: 55%

      DOI Reference: 10.1021/acs.jmedchem.0c01917

      Dog
      Dose: 0.3 mg/Kg
      Route of delivery: Intravenous
      Plasma half life: 8.48 h
      Systemic clearance: 6.02 mL/min/Kg
      Volume of Distribution at Steady-State: 3.13 L/Kg

      DOI Reference: 10.1021/acs.jmedchem.0c01917

      Dose: 1 mg/Kg
      Route of delivery: Oral
      Cmax: 223 ng/mL
      Area Under the Curve:: 2610 ng*h/mL
      Bioavailability: 87%

      DOI Reference: 10.1021/acs.jmedchem.0c01917

      Monkey (Cynomolgus)
      Dose: 0.3 mg/Kg
      Route of delivery: Intravenous
      Plasma half life: 2.72 h
      Systemic clearance: 16.3 mL/min/Kg
      Volume of Distribution at Steady-State: 2.87 L/Kg

      DOI Reference: 10.1021/acs.jmedchem.0c01917

      Dose: 0.3 mg/Kg
      Route of delivery: Oral
      Cmax: 30.7 ng/mL
      Area Under the Curve:: 337 ng*h/mL
      Bioavailability: 32%

      DOI Reference: 10.1021/acs.jmedchem.0c01917

      Negative Control Compounds

      cpd 10
      Notes: BACE1 IC50 1450 nM, Cell IC50 170 nM
      SMILES: CC1(C2=CC=CC(C(NC3=CC=C(Cl)C=N3)=O)=C2)N=C(N)SCC

      Chemical Information

      Molecular Formula C18H14FN5OS
      SMILEs C[C@@]1(c2cc(NC(=O)c3ccc(C#N)cn3)ccc2F)C=CSC(N)=N1
      InChI InChI=1S/C18H14FN5OS/c1-18(6-7-26-17(21)24-18)13-8-12(3-4-14(13)19)23-16(25)15-5-2-11(9-20)10-22-15/h2-8,10H,1H3,(H2,21,24)(H,23,25)/t18-/m0/s1
      Molecular weight 367.09 Da
      AlogP 3.135080000000001
      HBond acceptors 6
      HBond donors 3
      Atoms 40

      References

      Publications

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      Vendors

      Note: This is not an exhaustive list and does not indicate endorsement by the portal.

      Expert Reviews

      by SERP
      (on 14 Apr 2022 )
      Cellular Use Rating
      In Model Organisms
      Overall a good probe in terms of potency and PK profile. However, the lack of selectivity over BACE2 may lead to incorrect conclusions in phenotypic screens. It is recommended to use this probe with a...
      by SERP
      (on 1 May 2022 )
      Cellular Use Rating
      In Model Organisms
      This is a useful probe for BACE1 and BACE2 inhibition. Data obtained from the employment of this probe should be interpreted as inhibition of both targets, not just one.
      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