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Chemical Structure| 910462-43-0 Chemical Structure| 910462-43-0

Structure of Domatinostat
CAS No.: 910462-43-0

Chemical Structure| 910462-43-0

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Domatinostat is a selective class I HDAC inhibitor with IC50 of 1.20 μM, 1.12 μM, and 0.57 μM for HDAC1, HDAC2, and HDAC3, respectively. Also displays inhibitory activity against Lysine specific demethylase 1 (LSD1).

Synonyms: 4SC-202 free base; 4SC-202

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Product Details of Domatinostat

CAS No. :910462-43-0
Formula : C23H21N5O3S
M.W : 447.51
SMILES Code : O=C(NC1=CC=CC=C1N)/C=C/C2=CN(S(=O)(C3=CC=C(C4=CN(C)N=C4)C=C3)=O)C=C2
Synonyms :
4SC-202 free base; 4SC-202
MDL No. :MFCD28155264
InChI Key :PRXXYMVLYKJITB-IZZDOVSWSA-N
Pubchem ID :15985904

Safety of Domatinostat

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

Related Pathways of Domatinostat

epigenetics

Isoform Comparison

Biological Activity

Target
  • HDAC10

    HDAC10, IC50:21 μM

  • HDAC3

    HDAC3, IC50:0.57 μM

  • HDAC9

    HDAC9, IC50:50 μM

  • HDAC11

    HDAC11, IC50:9.7 μM

In Vitro:

Cell Line
Concentration Treated Time Description References
PANC1 and ASPC1 cells 0.5 μM and 1 μM 16 hours To evaluate the effect of Domatinostat on CD133 protein expression, results showed Domatinostat reduced CD133 expression. PMC9004159
HFOB 1.19 1 μM 24 h Inhibits cell growth and proliferation, increases histone H3 acetylation levels PMC8394112
SJSA-1 1 μM 24 h Inhibits cell growth and proliferation, increases histone H3 acetylation levels PMC8394112
Primary skin fibroblasts 2.5 μM 24 hours No G2M arrest or apoptosis observed PMC7987731
UM-MCC34 cells 2.5 μM 24 hours Induced G2M cell cycle arrest and apoptosis, upregulated APM component gene expression PMC7987731
MKL-2 cells 2.5 μM 24 hours Induced G2M cell cycle arrest and apoptosis, upregulated APM component gene expression PMC7987731
MKL-1 cells 2.5 μM 24 hours Induced G2M cell cycle arrest and apoptosis, upregulated APM component gene expression PMC7987731
WaGa cells 2.5 μM 24 hours Induced G2M cell cycle arrest and apoptosis, upregulated APM component gene expression PMC7987731
Panc1 cells 1 μM 24 or 72 hours 4SC-202 significantly inhibited the proliferation of Panc1 cells and induced p21 expression. PMC5499659
BxPC3 cells 1 μM 24 or 72 hours 4SC-202 significantly inhibited the proliferation of BxPC3 cells and induced p21 expression. PMC5499659
L3.6 cells 1 μM 24 or 72 hours 4SC-202 significantly inhibited the proliferation of L3.6 cells and induced p21 expression. PMC5499659
IMR90 human normal lung fibroblasts 500 nM 3 days Domatinostat did not affect cell viability PMC10341571
SKOV3 ovarian serous cancer cells 125-250 nM 3 days Domatinostat reduced FOXM1 mRNA and protein expression levels in a concentration-dependent manner PMC10341571
TOV21G ovarian clear cell cancer cells 125-250 nM 3 days Domatinostat reduced FOXM1 mRNA and protein expression levels in a concentration-dependent manner PMC10341571
Human lung fibroblasts (IMR90) 500 nM 3 days To evaluate the effect of Domatinostat on normal cells, results showed no significant impact on the growth of IMR90 cells at 500 nM. PMC9332065
Glioma stem cells (TGS01) 500 nM 3 days To evaluate the inhibitory effect of Domatinostat on the growth of glioma stem cells, results showed that Domatinostat significantly inhibited the growth of TGS01 cells at 500 nM. PMC9332065
Glioma stem cells (GS-Y03) 500 nM 3 days To evaluate the inhibitory effect of Domatinostat on the growth of glioma stem cells, results showed that Domatinostat significantly inhibited the growth of GS-Y03 cells at 500 nM. PMC9332065
Glioma stem cells (GS-Y01) 500 nM 3 days To evaluate the inhibitory effect of Domatinostat on the growth of glioma stem cells, results showed that Domatinostat significantly inhibited the growth of GS-Y01 cells at 500 nM. PMC9332065
MDA-MB-231 cells 100 nM to 10 µM 6 days To evaluate the cytotoxic and cytostatic effects of 4SC-202 on MDA-MB-231 cells, showing significant reduction in colony formation at concentrations of 100 nM to 10 µM PMC8996906
MCF10A cells 1 to 10 µM 7 days To evaluate the toxicity of 4SC-202 on normal breast epithelial cells, showing no cytotoxicity to MCF10A cells at concentrations ranging from 1 to 10 µM PMC8996906
PANC1 and ASPC1 spheroid cultures 0.5 μM 7 days To evaluate the effect of Domatinostat on pancreatic cancer stem cell spheroid formation, results showed Domatinostat reduced spheroid numbers. PMC9004159
4T1 cells 0.1 nM to 10 µM 72 hours To evaluate the cytotoxic effects of 4SC-202 on 4T1 cells, showing significant reduction in cell viability at concentrations ranging from 0.1 µM to 10 µM PMC8996906
PANC28 0.5 μM 96 hours To evaluate the anti-tumor effect of Domatinostat in combination with chemotherapeutic agents, showing synergistic anti-proliferative and pro-apoptotic effects. PMC8892808
ASPC1 0.5 μM 96 hours To evaluate the anti-tumor effect of Domatinostat in combination with chemotherapeutic agents, showing synergistic anti-proliferative and pro-apoptotic effects. PMC8892808
PANC1 0.5 μM 96 hours To evaluate the anti-tumor effect of Domatinostat in combination with chemotherapeutic agents, showing synergistic anti-proliferative and pro-apoptotic effects. PMC8892808
PANC1 and ASPC1 spheroids 0.5 μM and 1 μM To evaluate the effect of Domatinostat on spheroid viability, results showed Domatinostat reduced spheroid viability. PMC9004159

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
NMRI foxn1nu/nu mice Subcutaneous xenograft model of pancreatic cancer with L3.6 cells Oral gavage 120 mg/kg Twice daily for 4 days 4SC-202 significantly inhibited tumor growth. PMC5499659
Athymic mice PANC28 and PANC1 xenograft models Oral 20 mg/kg 5 days/week, for 3 weeks To evaluate the anti-tumor effect of Domatinostat in combination with chemotherapeutic agents, showing significant reduction in tumor volume and synergistic anti-tumor effects. PMC8892808
Athymic mice Pancreatic cancer xenograft model Oral 20 mg/kg 5 days/week for two weeks To evaluate the effect of Domatinostat alone or in combination with chemotherapy on pancreatic cancer xenografts, results showed Domatinostat enhanced chemotherapy efficacy. PMC9004159
BALB/c mice CT26 tumor model Oral 20 mg/kg twice daily or 60 mg/kg once daily 12-14 days (CT26) or up to 24 days (C38) Domatinostat reduced tumor volume in immunocompetent mice, increased the number of CTLs in the tumor core, improved the CTL/Treg ratio, and enhanced antitumor immune responses. PMC6839078
BALB/c mice 4T1 breast cancer model Intraperitoneal injection 50 mg/kg Three times per week for 21 days To evaluate the effects of 4SC-202 on tumor growth and metastasis, showing that 50 mg/kg dose significantly reduced tumor burden and lung metastasis PMC8996906
Athymic nude mice Human osteosarcoma xenograft model Intraperitoneal injection 50 mg/kg/day Once daily for 16 days Reduces tumor growth, tumor mass significantly decreased by 70.56% PMC8394112

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT01344707 Advanced Hematologic Malignanc... More >>ies Less << PHASE1 COMPLETED 2025-03-15 Universi?tsklinikum K?ln, K?ln... More >>, Germany|Robert-Bosch-Krankenhaus, Stuttgart, Germany|Universit?tsklinikum Würzburg, Würzburg, Germany Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.23mL

0.45mL

0.22mL

11.17mL

2.23mL

1.12mL

22.35mL

4.47mL

2.23mL

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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