Domatinostat (4SC-202)

Name: Domatinostat (4SC-202)
Brand: Selleck Chemicals
SKU: S7555
Rating: 5 (2 reviews)

For research use only.

Catalog No.S7555 Synonyms: Domatinostat

2 publications

Domatinostat (4SC-202) Chemical Structure

Molecular Weight(MW): 447.51

4SC-202 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). Phase 1.

Selleck's Domatinostat (4SC-202) has been cited by 2 publications

Purity & Quality Control

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Biological Activity

Description

Targets

HDAC3 ^[1] (Cell-free assay)	HDAC2 ^[1] (Cell-free assay)	HDAC1 ^[1] (Cell-free assay)	HDAC11 ^[1] (Cell-free assay)	HDAC5 ^[1] (Cell-free assay)	View More
0.57 μM	1.12 μM	1.20 μM	9.7 μM	11.3 μM	View More

In vitro

In HeLa cells, 4SC-202 induces hyperacetylation of histone H3 with EC50 of 1.1 μM. 4SC-202 induces a G2/M cell cycle arrest by interfering with the normal development of the mitotic spindle and causing collapsed spindle apparatus and multiple nucleation centres. In addition, 4SC-202 shows a broad anti-proliferative activity towards human cancer cell lines with a mean IC50 of 0.7 μM. ^[1]

Cell Data

Cell Lines	Assay Type	Incubation Time	Activity Description	PMID
CRL-2105	MV3D[YxtKH[rYXLpcIl1gSCjc4PhfS=>	NF\EVlc4OuLCiXi=	M3:yXWlEPTB;MUewJI5O	MkOyN\|A5QDV{NUC=
MyLa	Mo\sR4VtdCC4aXHibYxqfHliYYPzZZk>	NXSwbohvPzMkgJno	MoLSTWM2OD1zOUCgcm0>	NXiybWNmOzB6OEWyOVA>
CRL-8294	MXPD[YxtKH[rYXLpcIl1gSCjc4PhfS=>	MnnjO\|LjiImq	Mo\3TWM2OD1{NkCgcm0>	MYKzNFg5PTJ3MB?=
HTB-176	M3LNZmNmdGxidnnhZoltcXS7IHHzd4F6	MV23NwKBkWh?	NV\C[W9ZUUN3ME2zO\|Ahdk1?	MofPN\|A5QDV{NUC=
Se-Ax	MW\D[YxtKH[rYXLpcIl1gSCjc4PhfS=>	NXi4S3dZPzMkgJno	MnP3TWM2OD1{NUCgcm0>	MmTTN\|A5QDV{NUC=
HuT 78	MkW4R4VtdCC4aXHibYxqfHliYYPzZZk>	Mon3O\|LjiImq	NV7obXZzUUN3ME2zN\|Ahdk1?	MlzlN\|A5QDV{NUC=

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	Ac α-tubulin / Ac Histone H3 / Ac Histone H4 ; PubMed: 27250763 Target Oncol Levels of acetylated α-tubulin and histone H3 and H4 were quantified in VM-CUB1 and UM-UC-3 cells after defined 4SC-202 treatment (0.5/2.5 μM, 24/48 h). Treatment with 3 nM romidepsin served as positive control for H3 and H4 acetylation; treatment with 2.5 μM SAHA served as a positive control for acetylated α-tubulin. DMSO was the solvent control. Cyclin A / Cyclin B1 / Cyclin D1 / Cyclin E / p21 ; PubMed: 27250763 Target Oncol Cyclins (A, B1, D1, E) and p21 protein expression levels following 4SC-202 (0.5/2.5 μM) or 2.5 μM SAHA treatment were quantified by western blot analysis in comparison to DMSO treatment in VM-CUB1 and UM-UC-3 cells (24/48 h) Caspase-3 / Cleaved Caspase-3 / H3K4me2 / H3K9ac ; PubMed: 30885250 J Hematol Oncol Total cell lysates harvested after 48 h of drug treatment were subjected to immunoblot analysis using antibodies recognizing the indicated targets (H3K4me2: histone H3 dimethyl lysine 4; H3K9ac: histone H3 acetyl lysine 9)	27250763 30885250
Growth inhibition assay	Cell viability ; PubMed: 27250763 Target Oncol UCCs and control cells were treated with increasing amounts of the class I HDAC specific inhibitor 4SC-202. The dose–response curves after 72 h 4SC-202 treatment are shown exemplarily for the UCCs VM-CUB1 and UM-UC-3 and the non-urothelial control cells HBLAK and HEK-293. IC50; PubMed: 30885250 J Hematol Oncol IC50 doses for 4SC-202 and FK228-treated cells were calculated by nonlinear fitting of the MTS data	27250763 30885250

In vivo

In vivo, 4SC-202 has a high oral bioavailability, and shows high metabolic stability and a low plasma clearance. 4SC-202 (120 mg/kg p.o.) shows pronounced and robust anti-tumor activity in both A549 NSCLC xenograft and RKO27 colon carcinoma model. ^[1]

Protocol

Cell Research:

^[1]

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Cell lines: CRC lines (HT-29, HCT-116, HT-15, and DLD-1)
Concentrations: 0.1, 1, 5, 10 μM
Incubation Time: 72 hours
Method:
CRC cell lines (HT-29, HCT-116, HCT-15, and DLD1), the primary human colon cancer cells, or primary human colon epithelial cells were treated with applied concentrations of 4SC-202, cells were further cultured for indicated time, and cell survival was tested by MTT assay or trypan blue staining assay; cell proliferation was tested by clonogenicity assay. Expression of listed proteins was tested by Western blots.

(Only for Reference)

Animal Research:

^[1]

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Animal Models: A549 NSCLC xenograft model and RKO27 colon carcinoma model
Dosages: 120 mg/kg
Administration: p.o.
(Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	89 mg/mL (198.87 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 2% DMSO+30% PEG 300+5% Tween 80+ddH2O For best results, use promptly after mixing.	10mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download Domatinostat (4SC-202) SDF

Molecular Weight	447.51
Formula	C₂₃H₂₁N₅O₃S
CAS No.	910462-43-0
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	Domatinostat
Smiles	CN1C=C(C=N1)C2=CC=C(C=C2)S(=O)(=O)N3C=CC(=C3)C=CC(=O)NC4=CC=CC=C4N

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Step 2: Enter the in vivo formulation (Different batches have different solubility ratios, please contact Selleck to provide you with the correct ratio)

% DMSO+ % + % Tween 80+ % ddH₂O

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Calculation results:

Working concentration： mg/ml；

Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid 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 DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

Note：1.Please make sure the liquid is clear before adding the next solvent.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Bio Calculators

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

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Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

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This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

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Computed Result

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Molecular Weight Calculator

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Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
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Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2020-09-01)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT01344707	Completed	Drug: 4SC-202	Advanced Hematologic Malignancies	4SC AG	March 2011	Phase 1

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

Frequently Asked Questions

Question 1:
Do you have suggestions about the in vivo formulation of the compound?
Answer:
For in vivo study, we recommend to use 2% DMSO+30% PEG 300+5% Tween 80+ddH2O with solubility up to 10mg/ml.

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Domatinostat (4SC-202)