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Chemical Structure| 1316215-12-9 Chemical Structure| 1316215-12-9

Structure of Citarinostat
CAS No.: 1316215-12-9

Chemical Structure| 1316215-12-9

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Citarinostat selectively inhibits HDAC6 with IC50 of 4 nM. It can also inhibit HDAC3 (IC50 = 76 nM).

Synonyms: ACY241; HDAC-IN-2

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Product Details of Citarinostat

CAS No. :1316215-12-9
Formula : C24H26ClN5O3
M.W : 467.95
SMILES Code : O=C(C1=CN=C(N(C2=CC=CC=C2Cl)C3=CC=CC=C3)N=C1)NCCCCCCC(NO)=O
Synonyms :
ACY241; HDAC-IN-2
MDL No. :MFCD28023593
InChI Key :VLIUIBXPEDFJRF-UHFFFAOYSA-N
Pubchem ID :53340426

Safety of Citarinostat

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Citarinostat

epigenetics

Isoform Comparison

Biological Activity

Description
Citarinostat (ACY241) is an orally available, and highly selective inhibitor of HDAC6, showing an IC50 of 2.6 nM. Its selectivity extends across other HDAC isoforms as well, with IC50 values of 35 nM, 45 nM, 46 nM, and 137 nM for HDAC1, HDAC2, HDAC3, and HDAC8, respectively, suggesting its potential for anticancer applications[1].
Target
  • HDAC8

    HDAC8, IC50:137 nM

  • HDAC3

    HDAC3, IC50:46 nM

  • HDAC6

    HDAC6, IC50:2.6 nM

  • HDAC2

    HDAC2, IC50:45 nM

  • HDAC1

    HDAC1, IC50:35 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
S1-M1-80 cells 59.66 ± 10.32 µM 72 hours Evaluate the cytotoxicity of Citarinostat on S1-M1-80 cells PMC7961520
S1 cells 2.82 ± 0.40 µM 72 hours Evaluate the cytotoxicity of Citarinostat on S1 cells PMC7961520
KB-V-1 cells 57.96 ± 5.56 µM 72 hours Evaluate the cytotoxicity of Citarinostat on KB-V-1 cells PMC7961520
KB-3-1 cells 3.98 ± 0.73 µM 72 hours Evaluate the cytotoxicity of Citarinostat on KB-3-1 cells PMC7961520
CD4+ CD127loCD25+ Tregs 500nM 72 hours To evaluate the impact of HDAC6-selective inhibitors on regulatory T-cells (Tregs). Results showed that ACY-241 reduced Treg frequencies and FOXP3 expression and decreased their suppressive function. PMC6366050
T-cells from melanoma patient PBMCs 500nM 72 hours To evaluate the impact of HDAC6-selective inhibitors on T-cell viability and function. Results showed that ACY-241 did not impair T-cell viability at concentrations up to 1uM and reduced Th2 cytokine production (i.e. IL-4, IL-5, IL-6, IL-10 and IL-13). PMC6366050
Granta-519 0, 0.5, 1, 2, 4 µM 24-48 hours To evaluate the cytotoxicity of Citarinostat and Momelotinib alone and in combination on Granta-519 cells. Results showed that Granta-519 cells were less sensitive to the combination treatment (CI > 1), exhibiting an antagonistic effect. PMC7244621
WSU-NHL 0, 0.5, 1, 2, 4 µM 24-48 hours To evaluate the cytotoxicity of Citarinostat and Momelotinib alone and in combination on lymphoid malignant cell lines. Results showed that the combination of Citarinostat and Momelotinib exhibited synergistic effects (CI < 1) in most cell lines, significantly inhibiting cell viability and inducing apoptosis. PMC7244621
KP lung cancer cells 10 µg/ml 36 hours To evaluate the effect of ACY241 and Oxaliplatin on the effector function of tumor-associated T cells, results showed that ACY241 or Oxaliplatin alone enhanced the ability of CD8+ T cells to secrete TNFα and IFNγ, and the combination treatment had a more pronounced effect. PMC8865306
MDR19-HEK293 cells 33.83 ± 3.21 µM 72 hours Evaluate the cytotoxicity of Citarinostat on MDR19-HEK293 cells PMC7961520
HEK293 cells 3.01 ± 0.44 µM 72 hours Evaluate the effect of SR9009 on a luciferase reporter driven by the Bmal1 promoter PMC7961520
MM.1s 100-500 nM 18 hours Induced accumulation of ubiquitinated proteins PMC5338861
R482-HEK293 cells 20.11 ± 2.48 µM 72 hours Evaluate the cytotoxicity of Citarinostat on R482-HEK293 cells PMC7961520

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
CB.17 SCID mice H929 MM xenograft model Intraperitoneal injection 50 mg/kg Once daily for 42 consecutive days To evaluate the effect of combination treatment with ACY-241 and pomalidomide on tumor growth in the H929 MM xenograft model. Results showed that combination treatment significantly inhibited tumor growth without significant toxicity or adverse effects. PMC5338861
Mice KP lung cancer model Intraperitoneal injection 25 mg/kg ACY241 3 times/week for 3 weeks; Oxaliplatin 1 time/week for 6 weeks To evaluate the therapeutic effect of ACY241 alone or in combination with Oxaliplatin, results showed that combination therapy significantly prolonged the survival of mice and enhanced the effector function of tumor-associated T cells. PMC8865306

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.14mL

0.43mL

0.21mL

10.68mL

2.14mL

1.07mL

21.37mL

4.27mL

2.14mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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