Citarinostat | ACY-241 | CAS#1316215-12-9 | HDAC inhibitor

MedKoo Cat#: 206471 | Name: Citarinostat

Description:

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

Citarinostat, also known as ACY-241, is a potent, selective and orally available histone deacetylase (HDAC) inhibitor, with potential antineoplastic activity. Upon oral administration, ACY-241 inhibits the activity of HDACs; this results in an accumulation of highly acetylated chromatin histones, the induction of chromatin remodeling and an altered pattern of gene expression. This leads to the inhibition of tumor oncogene transcription, and the selective transcription of tumor suppressor genes, which inhibit tumor cell division and induce tumor cell apoptosis.

Chemical Structure

Citarinostat

CAS#1316215-12-9

Theoretical Analysis

MedKoo Cat#: 206471

Name: Citarinostat

CAS#: 1316215-12-9

Chemical Formula: C24H26ClN5O3

Exact Mass: 467.1724

Molecular Weight: 467.95

Elemental Analysis: C, 61.60; H, 5.60; Cl, 7.58; N, 14.97; O, 10.26

Price and Availability

Size	Price	Availability
10mg	USD 120.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 650.00	Ready to ship
200mg	USD 1,150.00	Ready to ship
500mg	USD 1,850.00	Ready to ship
1g	USD 2,750.00	Ready to ship
2g	USD 4,250.00	2 weeks

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Related CAS #

1316215-12-9

Synonym

ACY-241; ACY 241; ACY241; HDAC-IN-2; Citarinostat.

IUPAC/Chemical Name

2-((2-chlorophenyl)(phenyl)amino)-N-(7-(hydroxyamino)-7-oxoheptyl)pyrimidine-5-carboxamide

InChi Key

VLIUIBXPEDFJRF-UHFFFAOYSA-N

InChi Code

InChI=1S/C24H26ClN5O3/c25-20-12-7-8-13-21(20)30(19-10-4-3-5-11-19)24-27-16-18(17-28-24)23(32)26-15-9-2-1-6-14-22(31)29-33/h3-5,7-8,10-13,16-17,33H,1-2,6,9,14-15H2,(H,26,32)(H,29,31)

SMILES Code

ClC1=CC=CC=C1N(C2=CC=CC=C2)C3=NC=C(C=N3)C(NCCCCCCC(NO)=O)=O

Appearance

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#A8T11K02

QC Data

View QC data: current batch, Lot#A8T11K02

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Citarinostat (ACY241) is a HDAC6 inhibitor with an IC50 of 2.6 nM.

In vitro activity:

First, enzymatic inhibitory activities of ACY-241 and JQ1 were confirmed by observing their target proteins, acetyl α-tubulin and c-Myc, respectively. ACY-241 increased acetylation of α-tubulin, and JQ1 decreased c-Myc in both HPV-positive 2A3 and HPV-negative FaDu HNSCC (head and neck squamous carcinoma) cells. Furthermore, HDAC6 protein level remained unchanged by ACY-241 (Figure 2C,D). It has been previously reported that JQ1 did not modify BRD4 protein level. It was also confirmed that mRNA levels of HDAC6, BRD2, and BRD4 were unaffected after ACY-241 and JQ1 treatments (Figure S1A–C). As c-Myc oncogene is known to induce proliferation, we next performed immunoblotting to determine whether ACY-241 and JQ1 disrupt the apoptotic signaling pathway. PARP and caspase-3 were synergistically cleaved by combination treatment to exhibit pro-apoptotic effects. On the other hand, expression levels of anti-apoptotic proteins XIAP and Bcl-xL were synergistically reduced in both HPV-positive and HPV-negative HNSCC cells (Figure 3A,B). However, Bcl-2 associated pro-apoptotic proteins, such as Bak, Bax, and Bad, remained unchanged by ACY-241 and JQ1 combination (Figure S2). To further determine the apoptotic effect of HDAC6 and BET inhibition, flow cytometry analysis was performed to examine apoptosis after annexin V/propidium iodide staining. After 72 hours of combination treatment, early and late apoptosis were synergistically promoted in both HPV-positive and HPV-negative HNSCC cells. The percentage of apoptotic cells was as much as 9-fold higher than the additive effect of single inhibitor treatments (Figure 3C,D). Collectively, these data show that simultaneous inhibition of HDAC6 and BET is an effective treatment strategy to promote apoptosis in both HPV-positive and HPV-negative HNSCC cells. Reference: Int J Mol Sci. 2020 Sep 19;21(18):6873. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554925/

In vivo activity:

The efficacy of treating mice harboring H929 MM (multiple myeloma) xenografts with ACY-241 and/or pomalidomide was assessed. Mice harboring palpable tumors were treated with either vehicle, ACY-241 (50 mg/kg QD), pomalidomide (1 mg/kg QD), or both agents in combination. Consistent with reduced toxicity of selective HDAC inhibitors, no significant toxicity or adverse effects on the health of the animals as body weight increased while on treatment and no clinical signs were observed (Fig 5A). While ACY-241 did not significantly impact tumor growth as a single agent, pomalidomide treatment did suppress tumor growth relative to the vehicle treated group (Fig 5B). Importantly, combination treatment with ACY-241 plus pomalidomide resulted in significantly greater tumor growth inhibition relative to pomalidomide alone (Fig 5B). Reference: PLoS One. 2017 Mar 6;12(3):e0173507. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338861/

	Solvent	mg/mL	mM
Solubility
	DMSO	42.7	91.18
	Ethanol	93.0	198.74
	DMF	5.0	10.68
	DMSO:PBS (pH 7.2) (1:1)	0.5	1.07

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 467.95 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. Cho HY, Lee SW, Jeon YH, Lee DH, Kim GW, Yoo J, Kim SY, Kwon SH. Combination of ACY-241 and JQ1 Synergistically Suppresses Metastasis of HNSCC via Regulation of MMP-2 and MMP-9. Int J Mol Sci. 2020 Sep 19;21(18):6873. doi: 10.3390/ijms21186873. PMID: 32961679; PMCID: PMC7554925. 2. North BJ, Almeciga-Pinto I, Tamang D, Yang M, Jones SS, Quayle SN. Enhancement of pomalidomide anti-tumor response with ACY-241, a selective HDAC6 inhibitor. PLoS One. 2017 Mar 6;12(3):e0173507. doi: 10.1371/journal.pone.0173507. PMID: 28264055; PMCID: PMC5338861.

In vitro protocol:

In vivo protocol:

1. North BJ, Almeciga-Pinto I, Tamang D, Yang M, Jones SS, Quayle SN. Enhancement of pomalidomide anti-tumor response with ACY-241, a selective HDAC6 inhibitor. PLoS One. 2017 Mar 6;12(3):e0173507. doi: 10.1371/journal.pone.0173507. PMID: 28264055; PMCID: PMC5338861.

1: Pulya S, Amin SA, Adhikari N, Biswas S, Jha T, Ghosh B. HDAC6 as privileged target in drug discovery: A perspective. Pharmacol Res. 2021 Jan;163:105274. doi: 10.1016/j.phrs.2020.105274. Epub 2020 Nov 7. PMID: 33171304. 2: Cosenza M, Civallero M, Marcheselli L, Sacchi S, Pozzi S. Citarinostat and Momelotinib co-target HDAC6 and JAK2/STAT3 in lymphoid malignant cell lines: a potential new therapeutic combination. Apoptosis. 2020 Jun;25(5-6):370-387. doi: 10.1007/s10495-020-01607-3. PMID: 32394008; PMCID: PMC7244621. 3: Gordon MS, Shapiro GI, Sarantopoulos J, Juric D, Lu B, Zarotiadou A, Connarn JN, Le Bruchec Y, Dumitru CD, Harvey RD. Phase Ib Study of the Histone Deacetylase 6 Inhibitor Citarinostat in Combination With Paclitaxel in Patients With Advanced Solid Tumors. Front Oncol. 2022 Jan 7;11:786120. doi: 10.3389/fonc.2021.786120. PMID: 35070991; PMCID: PMC8779022. 4: Wu CP, Hung CY, Lusvarghi S, Chang YF, Hsiao SH, Huang YH, Hung TH, Yu JS, Ambudkar SV. Overexpression of Human ABCB1 and ABCG2 Reduces the Susceptibility of Cancer Cells to the Histone Deacetylase 6-Specific Inhibitor Citarinostat. Int J Mol Sci. 2021 Mar 5;22(5):2592. doi: 10.3390/ijms22052592. PMID: 33807514; PMCID: PMC7961520. 5: Awad MM, Le Bruchec Y, Lu B, Ye J, Miller JA, Lizotte PH, Cavanaugh ME, Rode AJ, Dumitru CD, Spira A. Corrigendum: Selective Histone Deacetylase Inhibitor ACY-241 (Citarinostat) Plus Nivolumab in Advanced Non-Small Cell Lung Cancer: Results From a Phase Ib Study. Front Oncol. 2022 Jun 7;12:889996. doi: 10.3389/fonc.2022.889996. Erratum for: Front Oncol. 2021 Sep 06;11:696512. PMID: 35747830; PMCID: PMC9210944. 6: Awad MM, Le Bruchec Y, Lu B, Ye J, Miller J, Lizotte PH, Cavanaugh ME, Rode AJ, Dumitru CD, Spira A. Selective Histone Deacetylase Inhibitor ACY-241 (Citarinostat) Plus Nivolumab in Advanced Non-Small Cell Lung Cancer: Results From a Phase Ib Study. Front Oncol. 2021 Sep 6;11:696512. doi: 10.3389/fonc.2021.696512. Erratum in: Front Oncol. 2022 Jun 07;12:889996. PMID: 34552864; PMCID: PMC8451476. 7: Nawar N, Bukhari S, Adile AA, Suk Y, Manaswiyoungkul P, Toutah K, Olaoye OO, Raouf YS, Sedighi A, Garcha HK, Hassan MM, Gwynne W, Israelian J, Radu TB, Geletu M, Abdeldayem A, Gawel JM, Cabral AD, Venugopal C, de Araujo ED, Singh SK, Gunning PT. Discovery of HDAC6-Selective Inhibitor NN-390 with in Vitro Efficacy in Group 3 Medulloblastoma. J Med Chem. 2022 Feb 24;65(4):3193-3217. doi: 10.1021/acs.jmedchem.1c01585. Epub 2022 Feb 4. PMID: 35119267. 8: Yoo J, Jeon YH, Lee DH, Kim GW, Lee SW, Kim SY, Park J, Kwon SH. HDAC6-selective inhibitors enhance anticancer effects of paclitaxel in ovarian cancer cells. Oncol Lett. 2021 Mar;21(3):201. doi: 10.3892/ol.2021.12462. Epub 2021 Jan 12. PMID: 33574940; PMCID: PMC7816281. 9: Laino AS, Betts BC, Veerapathran A, Dolgalev I, Sarnaik A, Quayle SN, Jones SS, Weber JS, Woods DM. HDAC6 selective inhibition of melanoma patient T-cells augments anti-tumor characteristics. J Immunother Cancer. 2019 Feb 6;7(1):33. doi: 10.1186/s40425-019-0517-0. PMID: 30728070; PMCID: PMC6366050. 10: North BJ, Almeciga-Pinto I, Tamang D, Yang M, Jones SS, Quayle SN. Enhancement of pomalidomide anti-tumor response with ACY-241, a selective HDAC6 inhibitor. PLoS One. 2017 Mar 6;12(3):e0173507. doi: 10.1371/journal.pone.0173507. PMID: 28264055; PMCID: PMC5338861. 11: Bag A, Schultz A, Bhimani S, Stringfield O, Dominguez W, Mo Q, Cen L, Adeegbe D. Coupling the immunomodulatory properties of the HDAC6 inhibitor ACY241 with Oxaliplatin promotes robust anti-tumor response in non-small cell lung cancer. Oncoimmunology. 2022 Feb 22;11(1):2042065. doi: 10.1080/2162402X.2022.2042065. PMID: 35223194; PMCID: PMC8865306. 12: Gawel JM, Shouksmith AE, Raouf YS, Nawar N, Toutah K, Bukhari S, Manaswiyoungkul P, Olaoye OO, Israelian J, Radu TB, Cabral AD, Sina D, Sedighi A, de Araujo ED, Gunning PT. PTG-0861: A novel HDAC6-selective inhibitor as a therapeutic strategy in acute myeloid leukaemia. Eur J Med Chem. 2020 Sep 1;201:112411. doi: 10.1016/j.ejmech.2020.112411. Epub 2020 Jun 6. PMID: 32615502. 13: Craig JM, Turner TH, Harrell JC, Clevenger CV. Prolactin Drives a Dynamic STAT5A/HDAC6/HMGN2 Cis-Regulatory Landscape Exploitable in ER+ Breast Cancer. Endocrinology. 2021 May 1;162(5):bqab036. doi: 10.1210/endocr/bqab036. PMID: 33589921. 14: Park SJ, Joo SH, Lee N, Jang WJ, Seo JH, Jeong CH. ACY-241, an HDAC6 inhibitor, overcomes erlotinib resistance in human pancreatic cancer cells by inducing autophagy. Arch Pharm Res. 2021 Dec;44(12):1062-1075. doi: 10.1007/s12272-021-01359-x. Epub 2021 Nov 10. PMID: 34761352.