ACY-738 | CAS# 1375465-91-0 | HDAC6 Inhibitor

MedKoo Cat#: 407295 | Name: ACY-738

Description:

WARNING: This product is for research use only, not for human or veterinary use.

ACY-738 is a potent and selective HDAC6 inhibitor with improved brain bioavailability. ACY-738 inhibits HDAC6 with low nanomolar potency and a selectivity of 60- to 1500-fold over class I HDACs. ACY-738 induces dramatic increases in α-tubulin acetylation in brain and stimulate mouse exploratory behaviors in novel, but not familiar environments.

Chemical Structure

ACY-738

CAS# 1375465-91-0

Theoretical Analysis

MedKoo Cat#: 407295

Name: ACY-738

CAS#: 1375465-91-0

Chemical Formula: C14H14N4O2

Exact Mass: 270.1117

Molecular Weight: 270.29

Elemental Analysis: C, 62.21; H, 5.22; N, 20.73; O, 11.84

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 750.00	Ready to ship
500mg	USD 1,650.00	Ready to ship
1g	USD 2,950.00	Ready to ship
2g	USD 5,250.00	Ready to ship

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

Synonym

ACY-738; ACY 738; ACY738.

IUPAC/Chemical Name

N-Hydroxy-2-[(1-phenylcyclopropyl)amino]-5-pyrimidinecarboxamide

InChi Key

LIIWIMDSZVNYHY-UHFFFAOYSA-N

InChi Code

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)

SMILES Code

O=C(C1=CN=C(NC2(C3=CC=CC=C3)CC2)N=C1)NO

Appearance

White to off-white solid powder

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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#B7B07C17

QC Data

View QC data: current batch, Lot#B7B07C17

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

ACY-738 inhibits HDAC6 with low nanomolar potency (IC50=1.7 nM) and a selectivity of 60- to 1500-fold over class I HDACs.

In vitro activity:

To confirm that the patient-derived L0 (high grade), S3 (high grade), and S7 (low grade) glioma cell lines are sensitive to HDAC6 inhibitors, dissociated cells in serum-free media were treated with different concentrations of ACY-738 (738). After five days, 0.5 to 5 µM treatment significantly reduced the size of L0 and S7 (Figure S1A–G) and S3 gliomaspheres (Figure S1K), suggesting decreased tumor cell proliferation. The proliferation of adherent murine KR158 glioma cells was also decreased following treatment with 5-µM 738 but remained unchanged with a lower concentration (500 nM) (Figure S1J). Compared to vehicle-treated cells, it was unexpectedly difficult to find aaTub+ cilia across S3, L0, and S7 human glioma cells following treatment with 738. The presence of aaTub+ cilia on S3 cells was reduced 1 h after treatment with 738 (Figure 1E). Importantly, the decrease in aaTub+ in cilia was not indicative of cilia loss because cilia were present and identified by co-labeling with an antibody against ADP ribosylation factor 13B (ARL13B) (Figure 1E). To assess whether HDAC6 inhibitors disrupted the microtubular structure of the ciliary axoneme, leading to the reduced aaTub observed by immunostaining, the cilia of treated cells were examined using TEM. The ciliary structure of L0 cells 24 h were fixed and examined after 5-µM 738 exposure; it was found that cilia with organized, longitudinally aligned arrays of microtubules along the axoneme (Figure S3A,B), suggesting that the ciliary microtubular structure was conserved following treatment with 738. Reference: Cancers (Basel). 2021 Apr 1;13(7):1644. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/33915983/

In vivo activity:

From 22 to 38weeks-of-age, mice were injected intraperitoneally with 5 or 20mg/kg of ACY-738, or vehicle control. Body weight and proteinuria were measured every 2weeks, while sera anti-dsDNA, Ig isotypes, and cytokine levels were measured every 4weeks. Kidney disease was determined by evaluation of sera, urine, immune complex deposition, and renal pathology. Flow cytometric analysis assessed thymic, splenic, bone marrow, and peripheral lymphocyte differentiation patterns. The results showed HDAC6 inhibition decreased SLE disease by inhibiting immune complex-mediated glomerulonephritis, sera anti-dsDNA levels, and inflammatory cytokine production and increasing splenic Treg cells. Inhibition of HDAC6 increased the percentage of cells in the early-stage developmental fractions of both pro- and pre-B cells. These results suggest that specific HDAC6 inhibition may be able to decrease SLE disease by altering aberrant T and B cell differentiation. Reference: Clin Immunol. 2016 Jan;162:58-73. https://linkinghub.elsevier.com/retrieve/pii/S1521-6616(15)30064-4

	Solvent	mg/mL	mM
Solubility
	DMSO	32.0	118.39

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 270.29 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:

In vitro protocol:

1. Shi P, Hoang-Minh LB, Tian J, Cheng A, Basrai R, Kalaria N, Lebowitz JJ, Khoshbouei H, Deleyrolle LP, Sarkisian MR. HDAC6 Signaling at Primary Cilia Promotes Proliferation and Restricts Differentiation of Glioma Cells. Cancers (Basel). 2021 Apr 1;13(7):1644. doi: 10.3390/cancers13071644. PMID: 33915983; PMCID: PMC8036575. 2. 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.

In vivo protocol:

1. Regna NL, Vieson MD, Luo XM, Chafin CB, Puthiyaveetil AG, Hammond SE, Caudell DL, Jarpe MB, Reilly CM. Specific HDAC6 inhibition by ACY-738 reduces SLE pathogenesis in NZB/W mice. Clin Immunol. 2016 Jan;162:58-73. doi: 10.1016/j.clim.2015.11.007. Epub 2015 Nov 22. PMID: 26604012.

1: LoPresti P. The Selective HDAC6 Inhibitor ACY-738 Impacts Memory and Disease Regulation in an Animal Model of Multiple Sclerosis. Front Neurol. 2019 Jun 28;10:519. doi: 10.3389/fneur.2019.00519. PMID: 31316445; PMCID: PMC6609573. 2: Regna NL, Vieson MD, Luo XM, Chafin CB, Puthiyaveetil AG, Hammond SE, Caudell DL, Jarpe MB, Reilly CM. Specific HDAC6 inhibition by ACY-738 reduces SLE pathogenesis in NZB/W mice. Clin Immunol. 2016 Jan;162:58-73. doi: 10.1016/j.clim.2015.11.007. Epub 2015 Nov 22. PMID: 26604012. 3: Majid T, Griffin D, Criss Z 2nd, Jarpe M, Pautler RG. Pharmocologic treatment with histone deacetylase 6 inhibitor (ACY-738) recovers Alzheimer's disease phenotype in amyloid precursor protein/presenilin 1 (APP/PS1) mice. Alzheimers Dement (N Y). 2015 Oct 11;1(3):170-181. doi: 10.1016/j.trci.2015.08.001. PMID: 29854936; PMCID: PMC5975056. 4: Sakloth F, Manouras L, Avrampou K, Mitsi V, Serafini RA, Pryce KD, Cogliani V, Berton O, Jarpe M, Zachariou V. HDAC6-selective inhibitors decrease nerve- injury and inflammation-associated mechanical hypersensitivity in mice. Psychopharmacology (Berl). 2020 Jul;237(7):2139-2149. doi: 10.1007/s00213-020-05525-9. Epub 2020 May 9. PMID: 32388618; PMCID: PMC7470631. 5: 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. 6: Regna NL, Vieson MD, Gojmerac AM, Luo XM, Caudell DL, Reilly CM. HDAC expression and activity is upregulated in diseased lupus-prone mice. Int Immunopharmacol. 2015 Dec;29(2):494-503. doi: 10.1016/j.intimp.2015.10.006. Epub 2015 Oct 21. PMID: 26471208; PMCID: PMC4666739. 7: Rossaert E, Pollari E, Jaspers T, Van Helleputte L, Jarpe M, Van Damme P, De Bock K, Moisse M, Van Den Bosch L. Restoration of histone acetylation ameliorates disease and metabolic abnormalities in a FUS mouse model. Acta Neuropathol Commun. 2019 Jul 5;7(1):107. doi: 10.1186/s40478-019-0750-2. PMID: 31277703; PMCID: PMC6612190. 8: Shi P, Hoang-Minh LB, Tian J, Cheng A, Basrai R, Kalaria N, Lebowitz JJ, Khoshbouei H, Deleyrolle LP, Sarkisian MR. HDAC6 Signaling at Primary Cilia Promotes Proliferation and Restricts Differentiation of Glioma Cells. Cancers (Basel). 2021 Apr 1;13(7):1644. doi: 10.3390/cancers13071644. PMID: 33915983; PMCID: PMC8036575. 9: Jochems J, Teegarden SL, Chen Y, Boulden J, Challis C, Ben-Dor GA, Kim SF, Berton O. Enhancement of stress resilience through histone deacetylase 6-mediated regulation of glucocorticoid receptor chaperone dynamics. Biol Psychiatry. 2015 Feb 15;77(4):345-55. doi: 10.1016/j.biopsych.2014.07.036. Epub 2014 Aug 28. PMID: 25442004; PMCID: PMC4297530. 10: Burg T, Rossaert E, Moisse M, Van Damme P, Van Den Bosch L. Histone Deacetylase Inhibition Regulates Lipid Homeostasis in a Mouse Model of Amyotrophic Lateral Sclerosis. Int J Mol Sci. 2021 Oct 18;22(20):11224. doi: 10.3390/ijms222011224. PMID: 34681883; PMCID: PMC8541517. 11: Lorenzo Pisarello M, Masyuk TV, Gradilone SA, Masyuk AI, Ding JF, Lee PY, LaRusso NF. Combination of a Histone Deacetylase 6 Inhibitor and a Somatostatin Receptor Agonist Synergistically Reduces Hepatorenal Cystogenesis in an Animal Model of Polycystic Liver Disease. Am J Pathol. 2018 Apr;188(4):981-994. doi: 10.1016/j.ajpath.2017.12.016. Epub 2018 Jan 31. PMID: 29366679; PMCID: PMC5963486. 12: 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. 13: Ren J, Catalina MD, Eden K, Liao X, Read KA, Luo X, McMillan RP, Hulver MW, Jarpe M, Bachali P, Grammer AC, Lipsky PE, Reilly CM. Selective Histone Deacetylase 6 Inhibition Normalizes B Cell Activation and Germinal Center Formation in a Model of Systemic Lupus Erythematosus. Front Immunol. 2019 Oct 25;10:2512. doi: 10.3389/fimmu.2019.02512. PMID: 31708928; PMCID: PMC6823248. 14: Maharaj K, Powers JJ, Achille A, Deng S, Fonseca R, Pabon-Saldana M, Quayle SN, Jones SS, Villagra A, Sotomayor EM, Sahakian E, Pinilla-Ibarz J. Silencing of HDAC6 as a therapeutic target in chronic lymphocytic leukemia. Blood Adv. 2018 Nov 13;2(21):3012-3024. doi: 10.1182/bloodadvances.2018020065. PMID: 30425065; PMCID: PMC6234358. 15: Ren J, Liao X, Vieson MD, Chen M, Scott R, Kazmierczak J, Luo XM, Reilly CM. Selective HDAC6 inhibition decreases early stage of lupus nephritis by down- regulating both innate and adaptive immune responses. Clin Exp Immunol. 2018 Jan;191(1):19-31. doi: 10.1111/cei.13046. Epub 2017 Oct 16. PMID: 28876451; PMCID: PMC5721231. 16: Guo W, Naujock M, Fumagalli L, Vandoorne T, Baatsen P, Boon R, Ordovás L, Patel A, Welters M, Vanwelden T, Geens N, Tricot T, Benoy V, Steyaert J, Lefebvre-Omar C, Boesmans W, Jarpe M, Sterneckert J, Wegner F, Petri S, Bohl D, Vanden Berghe P, Robberecht W, Van Damme P, Verfaillie C, Van Den Bosch L. HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS- ALS patients. Nat Commun. 2017 Oct 11;8(1):861. doi: 10.1038/s41467-017-00911-y. PMID: 29021520; PMCID: PMC5636840. 17: Maharaj K, Powers JJ, Mediavilla-Varela M, Achille A, Gamal W, Quayle S, Jones SS, Sahakian E, Pinilla-Ibarz J. HDAC6 Inhibition Alleviates CLL-Induced T-Cell Dysfunction and Enhances Immune Checkpoint Blockade Efficacy in the Eμ- TCL1 Model. Front Immunol. 2020 Nov 23;11:590072. doi: 10.3389/fimmu.2020.590072. PMID: 33329575; PMCID: PMC7719839. 18: Cook C, Carlomagno Y, Gendron TF, Dunmore J, Scheffel K, Stetler C, Davis M, Dickson D, Jarpe M, DeTure M, Petrucelli L. Acetylation of the KXGS motifs in tau is a critical determinant in modulation of tau aggregation and clearance. Hum Mol Genet. 2014 Jan 1;23(1):104-16. doi: 10.1093/hmg/ddt402. Epub 2013 Aug 19. PMID: 23962722; PMCID: PMC3857946. 19: 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.