Givinostat HCl

• CAS: 199657-29-9
• Catalog Number: ACM199657299
• Category: Inhibitors
• Molecular Weight: 457.96
• Molecular Formula: C24H28ClN3O4
• Description: Givinostat or gavinostat, aslo known as ITF2357, is a potent and orally active histone deacetylase inhibitor with potential anti-inflammatory, anti-angiogenic, and antineoplastic activities. It is a hydroxamate used in the form of its hydrochloride. Inhibition of HDAC activity by ITF2357 ameliorates joint inflammation and prevents cartilage and bone destruction in experimental arthritis.ITF2357 reduces cytokines and protects islet β cells in vivo and in vitro. ITF2357 decreases surface CXCR4 and CCR5 expression on CD4(+) T-cells and monocytes and is superior to valproic acid for latent HIV-1 expression in vitro.
• Synonyms: ITF2357; ITF-2357; ITF 2357; ITF2357 HCl; ITF2357 hydrochloride; Givinostat HCl
• IUPAC Name: (6-((diethylamino)methyl)naphthalen-2-yl)methyl (4-(hydroxycarbamoyl)phenyl)carbamate hydrochloride
• Canonical SMILES: O=C(OCC1=CC=C2C=C(CN(CC)CC)C=CC2=C1)NC3=CC=C(C(NO)=O)C=C3.[H]Cl
• InChI: InChI=1S/C24H27N3O4.ClH/c1-3-27(4-2)15-17-5-7-21-14-18(6-8-20(21)13-17)16-31-24(29)25-22-11-9-19(10-12-22)23(28)26-30;/h5-14,30H,3-4,15-16H2,1-2H3,(H,25,29)(H,26,28);1H
• InChI Key: QKSGNWJOQMSBEP-UHFFFAOYSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Alternative CAS: 497833-27-9 (free base); 199657-29-9 (HCl); 732302-99-7 (HCl hydrate)
• Biological Target: Givinostat (ITF-2357) hydrochloride is a HDAC inhibitor with an IC50 of 198 and 157 nM for HDAC1 and HDAC3, respectively.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 62.95; H, 6.16; Cl, 7.74; N, 9.18; O, 13.97
• Exact Mass: 457.1768
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: Givinostat significantly inhibited JS-1 cell proliferation and promoted cell apoptosis, leading to cell cycle arrest in G0/G1 phases.; Treatment with givinostat downregulated protein expression of CDK4, CDK6, and cyclin D1, whereas expression of p21 and p57 was; significantly increased. The givinostat-induced apoptosis of hepatic stellate cells was mainly mediated through p38 and extracellular; signal-regulated kinase 1/2. Givinostat treatment increased intracellular reactive oxygen species production, decreased mitochondrial; membrane potential, and promoted mitochondrial permeability transition pore opening. Acetylation of superoxide dismutase (acetyl; K68) and nuclear factor-κB p65 (acetyl K310) was upregulated, while there was no change in protein expression. Moreover, the; notable beneficial effect of givinostat on liver fibrosis was also confirmed in the mouse models.; Reference: World J Gastroenterol. 2015 Jul 21;21(27):8326-39. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26217084/
• In Vivo Activity: Mice were given 100 μL water or ITF2357 (5 mg/kg) by gavage and, after 1 h, injected intravenously with 200 μg/mouse of ConA.; Control mice received an intravenous injection of saline. Mice were bled 24 h later for evaluation of serum ALT levels as described; previously (33,34). As shown in Figure 15, ALT levels were reduced by more than 80% by ITF2357 pretreatment. In another; experiment, a comparison was made between 1 and 10 mg/kg of oral ITF2357. As shown in Figure 16, a dose of 1 mg/kg ITF2357; was as effective as a dose of 10 mg/kg in reducing ConA hepatitis as measured by ALT levels.; Reference: Mol Med. 2005 Jan-Dec;11(1-12):1-15. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/16557334/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).