Synonym
ACY-775; ACY 775; ACY775.
IUPAC/Chemical Name
2-((1-(3-Fluorophenyl)cyclohexyl)amino)-N-hydroxypyrimidine-5-carboxamide
InChi Key
IYBURCQQEUNLDL-UHFFFAOYSA-N
InChi Code
InChI=1S/C17H19FN4O2/c18-14-6-4-5-13(9-14)17(7-2-1-3-8-17)21-16-19-10-12(11-20-16)15(23)22-24/h4-6,9-11,24H,1-3,7-8H2,(H,22,23)(H,19,20,21)
SMILES Code
O=C(C1=CN=C(NC2(C3=CC=CC(F)=C3)CCCCC2)N=C1)NO
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
ACY-775 is an inhibitor of the of histone deacetylase 6 (HDAC6) with an IC50 of 7.5 nM.
In vitro activity:
The HDAC6 inhibitors, ACY-738 and ACY-775, hyperacetylated α-tubulin at a concentration of 1 μM. The histone acetylation was not affected (Fig. 1a–c). Immunocytochemistry was used to visualize the acetylation of α-tubulin, which is present in the cytoplasm, and of histone 3, visible in the nucleus. In vehicle-treated cells, α-tubulin was mainly present in the deacetylated form, while histone 3 was clearly acetylated (Fig. 1a, d). Upon treatment with ACY-738 and ACY-775, a clear enhancement of the acetylation of α-tubulin was visible, while histone acetylation remained unaltered (Fig. 1f–g).
Reference: Neurotherapeutics. 2017 Apr; 14(2): 417–428. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5398982/
In vivo activity:
When ACY-775 (50 mg/kg) was administered repeatedly in wild-type mice at 24 h, 4 h, and 30 min before killing, significant increases in α-tubulin acetylation were observed in all tested brain regions (Figure 2c): cortex, F2, 7=582.5, P<0.0001; hippocampus, F2, 7=260.4, P<0.0001; DRN, F2, 7=54.00, P<0.0001; and cerebellum, F2, 7=136.2, P<0.0001. In contrast, an identical treatment regimen in KO mice did not produce increases in α-tubulin acetylation over baseline levels (Figure 2c).
Reference: Neuropsychopharmacology. 2014 Jan; 39(2): 389–400. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870780/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
35.3 |
106.94 |
| DMF |
20.0 |
60.54 |
| DMF:PBS (pH 7.2) (1:4) |
0.2 |
0.61 |
| Ethanol |
34.5 |
104.43 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
330.36
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Benoy V, Vanden Berghe P, Jarpe M, Van Damme P, Robberecht W, Van Den Bosch L. Development of Improved HDAC6 Inhibitors as Pharmacological Therapy for Axonal Charcot-Marie-Tooth Disease. Neurotherapeutics. 2017 Apr;14(2):417-428. doi: 10.1007/s13311-016-0501-z. PMID: 27957719; PMCID: PMC5398982.
2. Jochems J, Boulden J, Lee BG, Blendy JA, Jarpe M, Mazitschek R, Van Duzer JH, Jones S, Berton O. Antidepressant-like properties of novel HDAC6-selective inhibitors with improved brain bioavailability. Neuropsychopharmacology. 2014 Jan;39(2):389-400. doi: 10.1038/npp.2013.207. Epub 2013 Aug 19. PMID: 23954848; PMCID: PMC3870780.
In vitro protocol:
1. Benoy V, Vanden Berghe P, Jarpe M, Van Damme P, Robberecht W, Van Den Bosch L. Development of Improved HDAC6 Inhibitors as Pharmacological Therapy for Axonal Charcot-Marie-Tooth Disease. Neurotherapeutics. 2017 Apr;14(2):417-428. doi: 10.1007/s13311-016-0501-z. PMID: 27957719; PMCID: PMC5398982.
2. Jochems J, Boulden J, Lee BG, Blendy JA, Jarpe M, Mazitschek R, Van Duzer JH, Jones S, Berton O. Antidepressant-like properties of novel HDAC6-selective inhibitors with improved brain bioavailability. Neuropsychopharmacology. 2014 Jan;39(2):389-400. doi: 10.1038/npp.2013.207. Epub 2013 Aug 19. PMID: 23954848; PMCID: PMC3870780.
In vivo protocol:
1. Benoy V, Vanden Berghe P, Jarpe M, Van Damme P, Robberecht W, Van Den Bosch L. Development of Improved HDAC6 Inhibitors as Pharmacological Therapy for Axonal Charcot-Marie-Tooth Disease. Neurotherapeutics. 2017 Apr;14(2):417-428. doi: 10.1007/s13311-016-0501-z. PMID: 27957719; PMCID: PMC5398982.
2. Jochems J, Boulden J, Lee BG, Blendy JA, Jarpe M, Mazitschek R, Van Duzer JH, Jones S, Berton O. Antidepressant-like properties of novel HDAC6-selective inhibitors with improved brain bioavailability. Neuropsychopharmacology. 2014 Jan;39(2):389-400. doi: 10.1038/npp.2013.207. Epub 2013 Aug 19. PMID: 23954848; PMCID: PMC3870780.
1: Jochems J, Boulden J, Lee BG, Blendy JA, Jarpe M, Mazitschek R, Van Duzer JH, Jones S, Berton O. Antidepressant-like properties of novel HDAC6-selective inhibitors with improved brain bioavailability. Neuropsychopharmacology. 2014 Jan;39(2):389-400. doi: 10.1038/npp.2013.207. Epub 2013 Aug 19. PMID: 23954848; PMCID: PMC3870780.
2: Benoy V, Vanden Berghe P, Jarpe M, Van Damme P, Robberecht W, Van Den Bosch L. Development of Improved HDAC6 Inhibitors as Pharmacological Therapy for Axonal Charcot-Marie-Tooth Disease. Neurotherapeutics. 2017 Apr;14(2):417-428. doi: 10.1007/s13311-016-0501-z. PMID: 27957719; PMCID: PMC5398982.
3: Tago T, Toyohara J, Ishii K. Preclinical Evaluation of an 18F-Labeled SW-100 Derivative for PET Imaging of Histone Deacetylase 6 in the Brain. ACS Chem Neurosci. 2021 Feb 17;12(4):746-755. doi: 10.1021/acschemneuro.0c00774. Epub 2021 Jan 27. PMID: 33502174.
4: Celen S, Rokka J, Gilbert TM, Koole M, Vermeulen I, Serdons K, Schroeder FA, Wagner FF, Bleeser T, Hightower BG, Hu J, Rahal D, Beyzavi H, Vanduffel W, Van Laere K, Kranz JE, Hooker JM, Bormans G, Cawthorne CJ. Translation of HDAC6 PET Imaging Using [18F]EKZ-001-cGMP Production and Measurement of HDAC6 Target Occupancy in Nonhuman Primates. ACS Chem Neurosci. 2020 Apr 1;11(7):1093-1101. doi: 10.1021/acschemneuro.0c00074. Epub 2020 Mar 19. PMID: 32159328; PMCID: PMC7205522.
5: Mithraprabhu S, Khong T, Jones SS, Spencer A. Histone deacetylase (HDAC) inhibitors as single agents induce multiple myeloma cell death principally through the inhibition of class I HDAC. Br J Haematol. 2013 Aug;162(4):559-62. doi: 10.1111/bjh.12388. Epub 2013 May 21. PMID: 23692150.
