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| 10mg |
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| 25mg |
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Purity: ≥98%
Citarinostat (ACY-241; ACY241; HDAC-IN-2) is a novel, potent, orally bioavailable and selective inhibitor of HDAC6 (histone deacetylase) with anticancer activity. It is presently being treated for multiple myeloma in a Phase 1b clinical trial (NCT 02400242). For HDAC6 and HDAC3, its IC50 values are 4 nM and 76 nM, respectively. Due to decreased potency against Class I HDACs, ACY-241 has the potential for a significantly lower side effect profile compared to current nonselective HDAC inhibitor drug candidates, similar to the structurally related analog ACY-1215 (ricolinostat). Despite this, ACY-241 may still be effective against cancer. Solid tumor growth is markedly suppressed when paclitaxel and either ricolinostat or ACY-241 are administered in combination to xenograft models. Compared to either drug alone, combination treatment with ACY-241 and paclitaxel improved the inhibition of proliferation and increased cell death in cell lines from various solid tumor lineages. In line with the observed rise in aneuploid cells, combination treatment with paclitaxel and ACY-241 also led to a higher frequency of mitotic cells with aberrant mitoses and abnormal multipolar spindles. The observation of NuMA-dependent and γ-tubulin-independent multipolar mitotic spindle formation at the molecular level suggests that centrosomal amplification is not a prerequisite for treatment-induced multipolar spindle formation. A compelling case can be made for the clinical development of ACY-241 plus paclitaxel in patients with advanced solid tumors, given the combination's significantly improved efficacy and the expected superior safety profile of a selective HDAC6 inhibitor over pan-HDAC inhibitors.
| Targets |
HDAC6 (IC50 = 2.6 nM); HDAC1 (IC50 = 35 nM); HDAC2 (IC50 = 45 nM); HDAC3 (IC50 = 46 nM); HDAC8 (IC50 = 137 nM); HDAC7 (IC50 = 7300 nM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
Citarinostat is an inhibitor that specifically targets HDAC6; its IC50 values for HDAC6 and HDAC3 are 4 nM and 76 nM, respectively.
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| Cell Assay |
Immunoblotting is done 24 hours after A2780 cells are cultivated with either a vehicle or a range of ACY-241 concentrations.
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| Animal Protocol |
Female athymic nude mice (7-week-old) injected with TOV-21G cells[1]
50 mg/kg Intraperitoneal injection; once daily for five days, followed by two days off; for 3 weeks |
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| References | ||
| Additional Infomation |
Citarinostat is under investigation in clinical trial NCT02886065 (A Study of PVX-410, a Cancer Vaccine, and Citarinostat +/- Lenalidomide for Smoldering MM).
Citarinostat is an orally available histone deacetylase (HDAC) inhibitor, with potential antineoplastic activity. Upon oral administration, citarinostat 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. HDAC, an enzyme upregulated in many tumor types, deacetylates chromatin histone proteins. |
| Molecular Formula |
C24H26CLN5O3
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| Molecular Weight |
467.17
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| Exact Mass |
467.172
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| Elemental Analysis |
C, 61.60; H, 5.60; Cl, 7.58; N, 14.97; O, 10.26
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| CAS # |
1316215-12-9
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| Related CAS # |
1316215-12-9;
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| PubChem CID |
53340426
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.624
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| LogP |
1.8
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
33
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| Complexity |
597
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=C([H])C([H])=C([H])C([H])=C1N(C1C([H])=C([H])C([H])=C([H])C=1[H])C1N=C([H])C(=C([H])N=1)C(N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(N([H])O[H])=O)=O
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| InChi Key |
VLIUIBXPEDFJRF-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
2-(N-(2-chlorophenyl)anilino)-N-[7-(hydroxyamino)-7-oxoheptyl]pyrimidine-5-carboxamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.34 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.34 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.34 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1405 mL | 10.7027 mL | 21.4055 mL | |
| 5 mM | 0.4281 mL | 2.1405 mL | 4.2811 mL | |
| 10 mM | 0.2141 mL | 1.0703 mL | 2.1405 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02886065 | Active Recruiting |
Drug: Hiltonol Drug: Citarinostat |
Smoldering Multiple Myeloma | Massachusetts General Hospital | March 7, 2017 | Phase 1 |
| NCT02551185 | Completed | Drug: ACY-241 | Advanced Solid Tumors | Celgene | December 22, 2015 | Phase 1 |
 Combination treatment with HDAC6 inhibitors and paclitaxel reduced tumor xenograft growth.Oncotarget.2017 Jan 10;8(2):2694-2707. |
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 Reduction of S-phase population, induction of cell death and impact on DNA content after combination treatment with ACY-241 and paclitaxel.Oncotarget.2017 Jan 10;8(2):2694-2707. |
 Combination treatment increased the frequency of multipolar mitotic spindle formation and abnormal nuclei.Oncotarget.2017 Jan 10;8(2):2694-2707. |
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