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Chemical Structure| 1375465-91-0 Chemical Structure| 1375465-91-0

Structure of ACY-738
CAS No.: 1375465-91-0

Chemical Structure| 1375465-91-0

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ACY-738 inhibits HDAC6 with IC50 value of 1.7 nM.

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Product Details of ACY-738

CAS No. :1375465-91-0
Formula : C14H14N4O2
M.W : 270.29
SMILES Code : O=C(C1=CN=C(NC2(C3=CC=CC=C3)CC2)N=C1)NO
MDL No. :MFCD28347706
InChI Key :LIIWIMDSZVNYHY-UHFFFAOYSA-N
Pubchem ID :57381425

Safety of ACY-738

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of ACY-738

epigenetics

Isoform Comparison

Biological Activity

Target
  • HDAC6

    HDAC6, IC50:1.7 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
N2a cells 3μM ACY-738 significantly increased acetylation levels of α-tubulin and histone 3 PMC6612190
RN46A-B14 cells 2.5μM 1 hour To test the effect of ACY-738 on GR nuclear translocation, results showed that ACY-738 significantly inhibited DEX-induced GR translocation. PMC4297530
RN46A-B14 cells 2.5 μM 4 hours To evaluate the effect of ACY-738 on α-tubulin acetylation. Results showed that ACY-738 significantly increased the acetylation of α-tubulin but had no significant effect on histone H3K9 acetylation. PMC3870780
Motor neurons 1 µM overnight ACY-738, an HDAC6 inhibitor, was used to rescue axonal transport defects in FUS-ALS patient-derived motor neurons. Results showed that ACY-738 treatment significantly increased the number of moving mitochondria and ER vesicles in motor neurons, restoring axonal transport function. PMC5636840
Mec2 cells 1 μM 24 hours ACY738 treatment significantly delayed growth kinetics, reduced cell-cycle progression, and arrested cells in G1 phase, increasing apoptosis. PMC6234358
OSU-CLL cells 1 μM 24 hours ACY738 treatment significantly delayed growth kinetics, reduced cell-cycle progression, and arrested cells in G1 phase, increasing apoptosis. PMC6234358
B cells and T cells 4 μM 24 hours ACY-738 treatment significantly decreased CO2 production from glucose oxidation in B cells and reduced CO2 production from fatty acid oxidation in both T cells and B cells. PMC6823248
HCT-116 cells 800 nM ACY-738 induces tubulin acetylation (a marker of HDAC6 inhibition) at 800nM, whereas histone acetylation (a marker of Class 1 HDAC inhibition) at that concentration is minimal. PMC6823248
Em-TCL1 B cells 0.5μM 24 hours To assess the effect of HDAC6 inhibition on antigen presentation by CLL B cells, results showed that ACY738 pre-treatment dose-dependently enhanced T-cell activation. PMC7719839
CLL patient B cells 0.5μM 24 hours To assess the effect of HDAC6 inhibition on surface markers of CLL patient B cells, results showed increased expression of MHCII and MHCI, and decreased expression of PD-L1. PMC7719839
OSU-CLL cells 0.5μM 24 hours To evaluate the effect of HDAC6 inhibition on CLL B cell engagement with T cells, results showed increased expression of MHCI, MHCII, and CD86, and decreased expression of PD-L1 and 41BB-L. PMC7719839
Mouse neuroblastoma (N2a) cells 1 μM overnight To assess the effect of ACY-738 on α-tubulin acetylation, results showed that ACY-738 significantly enhanced the acetylation of α-tubulin without affecting histone acetylation. PMC5398982
Mouse mesangial cells (MES 13) 0.5, 1 or 5 nM 2 hours pretreatment followed by 24 hours stimulation ACY-738 treatment increased Hsp90 acetylation, decreased iNOS protein, and reduced NF-κB nuclear translocation. PMC4666739
Mouse mesangial cells (MES 13) 1, 2, 5, 10 or 100 nM 24 hours ACY-738 at 5 nM significantly increased α-tubulin acetylation with little to no effect on histone H3 acetylation. PMC4666739
Dorsal root ganglion (DRG) neurons 2.5 μM overnight To evaluate the ability of ACY-738 to restore mitochondrial axonal transport defects, results showed that ACY-738 significantly increased mitochondrial motility and total number. PMC5398982

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Chronic social defeat stress model Intraperitoneal injection 5 mg/kg Once daily for 20 days To test the resilience-promoting effect of ACY-738 in social defeat stress, results showed that ACY-738-treated mice maintained higher interaction ratios, indicating enhanced resilience to stress. PMC4297530
Mice NIH Swiss mice and HDAC6 KO mice on C57BL/6J background Intraperitoneal injection 5 mg/kg and 50 mg/kg Single or repeated administration (24 h, 4 h, and 30 min before killing) To evaluate the effect of ACY-738 on α-tubulin acetylation in the brain and its antidepressant-like behavioral effects. Results showed that ACY-738 significantly increased α-tubulin acetylation in the brain and exhibited antidepressant-like effects in the tail suspension test and social defeat paradigm. These effects were fully abrogated in mice with a neural-specific loss of function of HDAC6. PMC3870780
Mice EuTCL1 transgenic mouse model Oral 25 mg/kg/day Once daily for 3 months ACY738 treatment significantly prolonged overall survival, reduced tumor burden and splenomegaly, decreased proliferation of malignant B cells, and increased sensitivity to apoptosis. PMC6234358
NZB/W F1 mice Systemic lupus erythematosus model Dietary administration 200 mg/kg Daily administration for 4 weeks ACY-738 treatment significantly reduced manifestations of lupus nephritis in NZB/W mice, decreased IgG and C3 deposition in glomeruli, and reduced plasma cell and germinal center formation in the spleen. PMC6823248
Mice TgFUS+/+ mouse model Oral 100 mg/kg Daily administration starting at symptom onset (P30) ACY-738 treatment significantly extended the lifespan of TgFUS+/+ mice, improved motor performance, and reduced weight loss PMC6612190
Mice Em-TCL1 adoptive transfer model Oral 25mg/kg/day Once daily for 2 weeks To evaluate the effect of HDAC6 inhibition on CLL progression, results showed that ACY738 delayed CLL progression, reduced PD-L1 expression, and lowered IL-10 levels. PMC7719839
Mice Mutant HSPB1-induced CMT2 mouse model Intraperitoneal injection 3 mg/kg Once daily for 21 days To assess the ability of ACY-738 to reverse motor and sensory deficits, results showed that ACY-738 significantly improved action potential amplitudes in motor and sensory nerves and increased reinnervation of neuromuscular junctions. PMC5398982
Mice Amyloid precursor protein/presenilin 1 (APP/PS1) mouse model Oral 100 mg/kg Daily for 21 days or 90 days To evaluate the effects of ACY-738 on axonal transport, behavior, and pathology. Results showed that ACY-738 treatment significantly improved axonal transport rates, recovered short-term learning and memory deficits, reduced hyperactivity, and modified tau and tubulin. PMC5975056
Mice Transgenic FUS mice (FUS+/+) expressing wild-type human FUS under the control of the mouse prion promoter (PrP) Oral 100 mg/kg Daily administration starting at symptom onset (30 days) until 60 days ACY-738 treatment restored histone acetylation, slowed down disease progression and significantly expanded the lifespan of transgenic FUS mice. Additionally, ACY-738 restored metabolic alterations in the spinal cord, specifically targeting glycerophospholipid metabolism and reducing cholesteryl esters accumulation. PMC8541517

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

3.70mL

0.74mL

0.37mL

18.50mL

3.70mL

1.85mL

37.00mL

7.40mL

3.70mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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