ACY-1083 |
Catalog No.GC34458
One-Click Copy Product Info
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ACY-1083 is a brain-penetrant, highly selective histone deacetylase 6 (HDAC6) inhibitor (IC₅₀≈3nM).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1708113-43-2
Sample solution is provided at 25 µL, 10mM.
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ACY-1083 is a brain-penetrant, highly selective histone deacetylase 6 (HDAC6) inhibitor (IC₅₀≈3nM). ACY-1083 inhibits HDAC6 to elevate α-tubulin acetylation, thereby improving microtubule/axonal transport and mitochondrial function. ACY-1083 is primarily used in mechanistic studies of HDAC6 function, chemotherapy-induced peripheral neuropathy (CIPN), and pharmacological research in nervous system injury-related models[1-4].
In vitro, during the oxygen-glucose deprivation/reoxygenation injury paradigm, ACY-1083 (30nM or 300nM) had been added to mouse hippocampal HT22 cells for 4h in the deprivation period. ACY-1083 had increased cell viability in a concentration-dependent manner, suppressed hypoxia-inducible factor-1α (HIF-1α) expression, and upregulated pro-survival signaling proteins such as phosphorylated mammalian target of rapamycin (p-mTOR) and heat shock protein 70 (HSP70)[5]. ACY-1083 (10μM) had been co-treated with TNF (5–50ng/ml) in human bronchial epithelial cells at the air-liquid interface for 8 days. ACY-1083 had reduced FITC-4kDa dextran paracellular permeability across the epithelium, and had attenuated TNF-stimulated secretion of IL-6, CCL2, and CXCL10[6].
In vivo, ACY-1083 (3mg/kg or 10mg/kg; once daily) had been intraperitoneally injected into adult male C57BL/6J mice with "stocking-glove" mechanical allodynia due to peripheral neuropathy for 7 or 14 consecutive days. ACY-1083 had effectively restored the mechanical withdrawal threshold in mice. ACY-1083 had elevated acetylated α-tubulin levels in the tibial nerve and improved mitochondrial oxygen consumption parameters (basal, ATP-coupled, proton leak, maximal respiration)[7]. ACY-1083 (10mg/kg/day; once daily) had been intraperitoneally injected into C57BL/6J mice in a doxorubicin-related cognitive impairment model for 14 consecutive days. ACY-1083 had significantly restored spatial/working memory and executive function in mice[8].
References:
[1] Vieson MD, Gojmerac AM, Khan D, et al. Treatment with a selective histone deacetylase 6 inhibitor decreases lupus nephritis in NZB/W mice. Histol Histopathol. 2017 Dec;32(12):1317-1332.
[2] Biesterveld BE, Wakam GK, Kemp MT, et al. Histone deacetylase 6 inhibition improves survival in a swine model of lethal hemorrhage, polytrauma, and bacteremia. J Trauma Acute Care Surg. 2020 Nov;89(5):932-939.
[3] Porter NJ, Mahendran A, Breslow R, et al. Unusual zinc-binding mode of HDAC6-selective hydroxamate inhibitors. Proc Natl Acad Sci U S A. 2017 Dec 19;114(51):13459-13464.
[4] Martinez VK, McAlpin BR, Singh AK, et al. Single-Nucleus RNA Sequencing of HDAC6 Inhibition in Resolving Doxorubicin-Induced Cognitive Impairment. Mol Neurobiol. 2025 Oct;62(10):13557-13575.
[5] Nikolian VC, Dennahy IS, Weykamp M, et al. Isoform 6-selective histone deacetylase inhibition reduces lesion size and brain swelling following traumatic brain injury and hemorrhagic shock. J Trauma Acute Care Surg. 2019 Feb;86(2):232-239.
[6] Horndahl J, Svärd R, Berntsson P, et al. HDAC6 inhibitor ACY-1083 shows lung epithelial protective features in COPD. PLoS One. 2022 Oct 12;17(10):e0266310.
[7] Krukowski K, Ma J, Golonzhka O, et al. HDAC6 inhibition effectively reverses chemotherapy-induced peripheral neuropathy. Pain. 2017 Jun;158(6):1126-1137.
[8] McAlpin BR, Mahalingam R, Singh AK, et al. HDAC6 inhibition reverses long-term doxorubicin-induced cognitive dysfunction by restoring microglia homeostasis and synaptic integrity. Theranostics. 2022 Jan 1;12(2):603-619.
| Cell experiment [1]: | |
Cell lines | HT22 cells (mouse hippocampal immortalized cell line) |
Preparation Method | HT22 cells were maintained in Dulbecco's modified Eagle medium (DMEM) supplemented with 10% fetal calf serum, 100U/mL penicillin, and 100μg/mL streptomycin at 37°C, 95% air/5% CO₂. HT22 cells were seeded in plates and, after 24h, subjected to oxygen–glucose deprivation (0% O₂, 95% N₂, 5% CO₂, glucose-free medium, 0.5% serum, 18h) followed by re-oxygenation (21% O₂, normal culture medium, 4h). During the OGD period, culture medium was supplemented with ACY-1083 at 30nM or 300nM. |
Reaction Conditions | 30 or 300nM; 4h |
Applications | ACY-1083 increased HT22 cell viability in a dose-dependent manner. ACY-1083 at 300nM significantly suppressed HIF-1α expression and up-regulated the pro-survival effectors HSP70, phosphorylated mTOR, supporting a cytoprotective, pro-survival phenotype under oxygen–glucose deprivation stress. |
| Animal experiment [2]: | |
Animal models | Female C57BL/6J mice |
Preparation Method | Mice were first intraperitoneally administered doxorubicin hydrochloride (5mg/kg/week) for 4 consecutive weeks (cumulative 20mg/kg) followed by 1 week of rest, and then intraperitoneally administered ACY-1083 (10mg/kg/day) once daily for 14 days; behavioral testing (puzzle box test and novel object/place recognition test) was performed beginning 4 weeks after the final ACY-1083 dose, and mice were euthanized 6 weeks after the final ACY-1083 dose for perfusion fixation and brain/tissue analysis. |
Dosage form | 10mg/kg/day; i.p.; once daily for 14 days |
Applications | ACY-1083 reversed long-term doxorubicin-induced deficits in executive function/spatial memory (puzzle box test) and in spatial/working memory (novel object/place recognition test), restored hippocampal CA3 postsynaptic marker PSD95 expression, and reversed doxorubicin-associated microglial deramification/loss of ramification and a stage-1 DAM–like transcriptomic shift toward a more homeostatic microglial state. |
References: | |
| Cas No. | 1708113-43-2 | SDF | |
| Canonical SMILES | FC(CC1)(F)CCC1(NC2=NC=C(C(NO)=O)C=N2)C3=CC=CC=C3 | ||
| Formula | C17H18F2N4O2 | M.Wt | 348.35 |
| Solubility | DMSO: 100 mg/mL (287.07 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8707 mL | 14.3534 mL | 28.7068 mL |
| 5 mM | 574.1 μL | 2.8707 mL | 5.7414 mL |
| 10 mM | 287.1 μL | 1.4353 mL | 2.8707 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 22 reference(s) in Google Scholar.)