Givinostat (ITF2357)

Catalog No.S2170

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.

Price Stock Quantity  
USD 320 In stock
USD 170 In stock
USD 320 In stock
USD 970 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

Givinostat (ITF2357) Chemical Structure

Givinostat (ITF2357) Chemical Structure
Molecular Weight: 475.97

Validation & Quality Control

3 customer reviews :

Quality Control & MSDS

Related Compound Libraries

Givinostat (ITF2357) is available in the following compound libraries:

HDAC Inhibitors with Unique Features

Product Information

  • Compare HDAC Inhibitors
    Compare HDAC Products
  • Research Area
  • Inhibition Profile

Product Description

Biological Activity

Description 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.
Targets HD1-B [1]
(Cell-free assay)
HD2 [1]
(Cell-free assay)
HD1-A [1]
(Cell-free assay)
IC50 7.5 nM 10 nM 16 nM
In vitro In LPS-stimulated cultured human peripheral blood mononuclear cells (PBMCs), ITF2357 reduces the release of TNFα, IL-1α, IL-1β, and IFNγ, with IC50 of 10-25 nM, respectively. Using the combination of IL-12 plus IL-18, ITF2357 reduces IFNγ and IL-6 production with IC50 of 12.5-25 nM, independent of decreased IL-1 or TNFα. [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 IFNγ in mesenchymal stromal cells (MSCs) by 80-95%. [2] ITF2357 favors β-cell survival during inflammatory conditions. ITF2357 at concentrations of 25 and 250 nM increases islet cell viability, enhances insulin secretion, inhibits release of MIP-1α and MIP-2, reduces NO production and decreases apoptosis rates. [3]
In vivo ITF2357 (1-10 mg/kg) reduces LPS-induced serum TNFα and IFNγ 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]
Features An orally active, potent inhibitor of histone deacetylases (HDACs).

Protocol(Only for Reference)

Kinase Assay: [1]

Enzymatic Assay for HDAC Inhibitory Activity of Synthetic Compounds The assay is performed by adding 100 μL substrate (2×105 cpm), 40 μL buffer (50 mM Tris-HCl, pH 8.0, 750 mM NaCl, 5 mM PMSF, 50% glycerol) and 95 μL distilled water to the crude cellular extract (5 μL). ITF2357 (50 μL) is added to test for HDAC inhibition. The mixture is incubated overnight at room temperature and the reaction quenched by adding 50 μL of a solution containing 259 μL 37% HCl and 28 μL acetic acid in 1 mL distilled water. The [3H]acetyl residues released from the substrate are separated by organic extraction with 600 μL of ethyl acetate, 200 μL 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).

Cell Assay: [1]

Cell lines peripheral blood mononuclear cells (PBMCs)
Concentrations 1 nM - 1 μM
Incubation Time 24 hours
Method After washing, the isolated PBMCs are resuspended in RPMI containing 5% FCS at 5×106/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 μL 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 μL per well. The supernatants are removed after incubation at 37 °C for 24 hours, and frozen at -80 °C until assayed for cytokines.

Animal Study: [1]

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.
Formulation Dissolved in water
Dosages 0.01-50 mg/kg
Administration By gavage in 100 μL water.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Leoni F, et al. Mol Med, 2005, 11(1-12), 1-15.

[2] Golay J, et al. Leukemia, 2007,21(9), 1892-1900.

view more

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-30)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT01901432 Recruiting Polycythemia Vera Italfarmaco October 2013 Phase 1|Phase 2
NCT01761292 Active, not recruiting Duchenne Muscular Dystrophy (DMD) Italfarmaco May 2013 Phase 1|Phase 2
NCT01761968 Recruiting Chronic Myeloproliferative Neoplasms Italfarmaco March 2013 Phase 2
NCT01557452 Terminated Juvenile Idiopathic Arthritis Italfarmaco|Parexel December 2011 --
NCT01261624 Terminated Polyarticular Course Juvenile Idiopathic Arthritis Italfarmaco October 2010 Phase 2

view more

Chemical Information

Download Givinostat (ITF2357) SDF
Molecular Weight (MW) 475.97
Formula

C24H27N3O4.HCl.H2O

CAS No. 732302-99-7
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 95 mg/mL (199.59 mM)
Ethanol 3 mg/mL (6.3 mM)
Water <1 mg/mL (<1 mM)
In vivo 30% propylene glycol, 5% Tween 80, 65% D5W 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* 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 Name (6-((diethylamino)methyl)naphthalen-2-yl)methyl 4-(hydroxycarbamoyl)phenylcarbamate hydrochloride hydrate

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.

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

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

* Indicates a Required Field

Related HDAC Products

  • LMK-235

    LMK-235 is a selective inhibitor of HDAC4 and HDAC5 with IC50 of 11.9 nM and 4.2 nM, respectively.

  • CAY10603

    CAY10603 is a potent and selective HDAC6 inhibitor with IC50 of 2 pM, >200-fold selectivity over other HDACs.

  • 4SC-202

    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.

  • Panobinostat (LBH589)

    Panobinostat (LBH589) is a novel broad-spectrum HDAC inhibitor with IC50 of 5 nM in a cell-free assay. Phase 3.

  • Vorinostat (SAHA, MK0683)

    Vorinostat (suberoylanilide hydroxamic acid, SAHA) is an HDAC inhibitor with IC50 of ~10 nM in a cell-free assay.

  • Entinostat (MS-275)

    Entinostat (MS-275) strongly inhibits HDAC1 and HDAC3 with IC50 of 0.51 μM and 1.7 μM in cell-free assays, compared with HDACs 4, 6, 8, and 10. Phase 3.

  • Trichostatin A (TSA)

    Trichostatin A (TSA) is an HDAC inhibitor with IC50 of ~1.8 nM in cell-free assays.

  • Romidepsin (FK228, Depsipeptide)

    Romidepsin (FK228, depsipeptide) is a potent HDAC1 and HDAC2 inhibitor with IC50 of 36 nM and 47 nM in cell-free assays, respectively.

    Features:More effective than other classical HDAC inhibitors such as TSA, TPX, and butyrate.

  • RGFP966

    RGFP966 is an HDAC3 inhibitor with IC50 of 0.08 μM in cell-free assay, exhibits > 200-fold selectivity over other HDAC.

  • Tubastatin A

    Tubastatin A is a potent and selective HDAC6 inhibitor with IC50 of 15 nM in a cell-free assay. It is selective against all the other isozymes (1000-fold) except HDAC8 (57-fold).

Recently Viewed Items

Tags: buy Givinostat (ITF2357) | Givinostat (ITF2357) supplier | purchase Givinostat (ITF2357) | Givinostat (ITF2357) cost | Givinostat (ITF2357) manufacturer | order Givinostat (ITF2357) | Givinostat (ITF2357) distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Contact Us