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Givinostat hydrochloride monohydrate

Givinostat hydrochloride monohydrate

ArtNr	S2170-200
Hersteller	Selleckchem
CAS-Nr.	732302-99-7
Menge	200 mg
Quantity options	10 mg 100 mg 1 g 10 g 10 mM/1 mL 200 mg 25 mg 5 mg 50 mg 5 g
Kategorie	Oncology Neuroscience Neuroinflammation Metabolism Diabetes Glucose Homeostasis Cholesterol & Lipid Metabolism Regulation of Appetite Inhibitors & Compound Libraries Small Molecules By Organ Lung Cancer Bladder Cancer Colorectal Cancer Heart & Blood Cancer Testicular & Prostate Cancer Lymphatic System Cancer
Typ	Inhibitors
Specific against	other
Smiles	CCN(CC)CC1=CC2=C(C=C1)C=C(C=C2)COC(=O)NC3=CC=C(C=C3)C(=O)NO.O.Cl
ECLASS 10.1	32160490
ECLASS 11.0	32160490
UNSPSC	12000000
Alias	HDAC,HDAC
Similar products	ITF2357
Lieferbar
Storage Conditions	2 years -80 in solvent
Molecular Weight	475, 97
Administration	By gavage in 100 uL water.
Animal Models	Mice. For LPS induction of serum cytokines: BALB/c, for anti-CD3-induced cytokines: CD1, for concanavalin A (Con A)-induced acute hepatitis: BALB/c or C57Bl6.
Cell lines	peripheral blood mononuclear cells (PBMCs)
Clinical Trials	A Phase II clinical trial of ITF2357 in active systemic onset juvenile idiopathic arthritis (SOJIA) has been completed.
Concentrations	1 nM - 1 uM
Dosages	0.01-50 mg/kg
Formulation	Dissolved in water
IC50	7.5 to 16 nM [1], 7.5 to 16 nM [1], 7.5 to 16 nM [1], 7.5 to 16 nM [1], 7.5 to 16 nM [1], 7.5 to 16 nM [1]
In vitro	In LPS-stimulated cultured human peripheral blood mononuclear cells (PBMCs), ITF2357 reduces the release of TNFalpha, IL-1alpha, IL-1beta, and IFNgamma, with IC50 of 10-25 nM, respectively. Using the combination of IL-12 plus IL-18, ITF2357 reduces IFNgamma and IL-6 production with IC50 of 12.5-25 nM, independent of decreased IL-1 or TNFalpha. [1] ITF2357 is cytotoxic in multiple myeloma (MM) cell lines (RPMI8226, NCI-H929, JJN3, KMS 11, KMS 12, KMS 18, and KMS 20) and acute myelogenous leukemia (AML) cell lines (HL-60, THP-1, U937, KASUMI, KG-1, and TF-1), with IC50 of 200 nM. ITF2357 activates the intrinsic apoptotic pathway, upregulates p21 and downmodulates Bcl-2 and Mcl-1. ITF2357 inhibits the production of IL-6, VEGF, and IFNgamma in mesenchymal stromal cells (MSCs) by 80-95%. [2] ITF2357 favors beta-cell survival during inflammatory conditions. ITF2357 at concentrations of 25 and 250 nM increases islet cell viability, enhances insulin secretion, inhibits release of MIP-1alpha and MIP-2, reduces NO production and decreases apoptosis rates. [3]
In vivo	ITF2357 (1-10 mg/kg) reduces LPS-induced serum TNFalpha and IFNgamma by more than 50% in mice. Anti-CD3-induced cytokines are not suppressed by ITF2357 in PBMCs in the circulation in mice. In concanavalin-A-induced hepatitis, ITF2357 (1 or 5 mg/kg) significantly reduces liver damage. [1] ITF2357 (10 mg/kg) significantly prolongs survival of severe combined immunodeficient mice inoculated with the AML-PS in vivo passaged cell line. [2] In a mouse model of closed head injury (CHI), ITF2357 (10 mg/kg) improves neurobehavioral recovery, decreases neuronal degeneration, reduces lesion volume, and induces glial apoptosis. [4]
Incubation Time	24 hours
Kinase Assay	Enzymatic Assay for HDAC Inhibitory Activity of Synthetic Compounds, The assay is performed by adding 100 uL substrate (2x105 cpm), 40 uL buffer (50 mM Tris-HCl, pH 8.0, 750 mM NaCl, 5 mM PMSF, 50% glycerol) and 95 uL distilled water to the crude cellular extract (5 uL). ITF2357 (50 uL) is added to test for HDAC inhibition. The mixture is incubated overnight at room temperature and the reaction quenched by adding 50 uL of a solution containing 259 uL 37% HCl and 28 uL acetic acid in 1 mL distilled water. The [3H]acetyl residues released from the substrate are separated by organic extraction with 600 uL of ethyl acetate, 200 uL of the organic phase is added to standard scintillation fluid, and radioactivity is measured by a beta-counter. Inhibition of HDACs is expressed as the concentration inhibiting 50% of the control activity (by comparing the radioactivity of the samples containing inhibitors to that of the control containing cellular crude extract alone).
Method	After washing, the isolated PBMCs are resuspended in RPMI containing 5% FCS at 5x106/mL, added to a 50-mL conical polypropylene tube, and placed at 4 C overnight. The PBMCs are resuspended the next morning and added to a 96-well flat microtiter plate (100 uL per well). ITF2357 is then added for inhibition studies, and the plates are incubated at 37 C for 1 hour, after which the cells are stimulated with LPS or other stimulants in a final volume of 200 uL per well. The supernatants are removed after incubation at 37 C for 24 hours, and frozen at -80 C until assayed for cytokines.
Solubility (25C)	DMSO 95 mg/mL, Water <1 mg/mL, Ethanol 3 mg/mL
Information	Givinostat (ITF2357) is a potent HDAC inhibitor for maize HD2, HD1B and HD1A with IC50 of 10 nM, 7.5 nM and 16 nM in cell-free assays. Phase 2.
Chemical Name	(6-((diethylamino)methyl)naphthalen-2-yl)methyl 4-(hydroxycarbamoyl)phenylcarbamate hydrochloride hydrate
Features	ITF2357 is an orally active, potent inhibitor of histone deacetylases (HDACs).

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