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ACY-738 | Inhibitor of HDAC6
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (3 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
HDAC6
  • IC50:1.7 nM
Inhibitor
10 nM - 1 uM

Selectivity

In Vitro Selectivity Assessment

Potency: IC50 - HDAC1: 94 nM, HDAC2: 128 nM, HDAC3: 218 nM

Potency Assay Off-Target:
Enzyme assay, recombinant protein
In Cell Selectivity Assessment
Potency Assay Off-Target:
In RN46A-B12 cells, ACY-738 (2.5 uM) did not affect histone H3K9 acetylation.

Potency
Cellular
In Vitro

HDAC6

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? No

In Vivo Validations

male NIH Swiss mice
Dose: 5 mg/kg
Route of delivery: Intraperitoneal
Plasma half life: 0.2 h
Organ of interest (O): Brain
Target engagement assay: In whole-brain lysate after treatment, alpha-tubulin acetylation increased in multiple brain regions (cortex, hippocampus, DRN, and cerebellum). An increase in alpha-tubulin acetlyation was not observed in the brains of flHDAC6^nestin-cre mice (neural-crest specific HDAC6 knock out in C57BL6 mice) beyond the already elevated levels. No changes in the acetylation of H3K9 were detected.

Reference: --

Negative Control Compounds

CANSAR1573319

Orthogonal Probes def

SS-208
TUBACIN
TUBASTATIN A

Chemical Information

Molecular Formula C14H14N4O2
SMILEs O=C(NO)c1cnc(NC2(c3ccccc3)CC2)nc1
InChI InChI=1S/C14H14N4O2/c19-12(18-20)10-8-15-13(16-9-10)17-14(6-7-14)11-4-2-1-3-5-11/h1-5,8-9,20H,6-7H2,(H,18,19)(H,15,16,17)
Molecular weight 270.11 Da
AlogP 1.6967999999999999
HBond acceptors 6
HBond donors 3
Atoms 34

References

Publications

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    Expert Reviews

    by SERP
    (on 30 Apr 2017 )
    Cellular Use Rating
    In Model Organisms
    ACY-738 is a very potent HDAC6 inhibitor (IC50 of 1.7 nM) with >50-100X selectivity against other HDAC isoforms. It has poor PK, and thus has to be administered by either IV or IP routes. Calculated...
    by SERP
    (on 11 May 2017 )
    Cellular Use Rating
    In Model Organisms
    ( The reviewer did not leave any comments )
    by SERP
    (on 14 May 2017 )
    Cellular Use Rating
    In Model Organisms
    While this probe is highly potent for the intended target in vitro, the cellular potency is not discerned as these experiments were only carried out at a single dose (2.5 microM). I would like to see...
    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