Belinostat

• CAT Number: I005210
• CAS Number: 866323-14-0
• Molecular Formula: C15H14N2O4S
• Molecular Weight: 318.347
• Purity: ≥95%
• Target: pan-HDAC
• Solubility: DMSO ≥60mg/mL Water <1.2mg/mL Ethanol <1.2mg/mL
• Storage: Store at -20C
• IC50: 27 nM
• IUPAC Name: (E)-N-hydroxy-3-[3-(phenylsulfamoyl)phenyl]prop-2-enamide
• InChI: InChI=1S/C15H14N2O4S/c18-15(16-19)10-9-12-5-4-8-14(11-12)22(20,21)17-13-6-2-1-3-7-13/h1-11,17,19H,(H,16,18)/b10-9+
• InChIKey: NCNRHFGMJRPRSK-MDZDMXLPSA-N
• SMILES: C1=CC=C(C=C1)NS(=O)(=O)C2=CC=CC(=C2)C=CC(=O)NO

Belinostat (PXD101) is a novel pan-HDAC inhibitor with IC50 of 27 nM, with activity demonstrated in cisplatin-resistant tumors.IC50 Value: 27 nMTarget: pan-HDACin vitro: Belinostat inhibits the growth of tumor cells (A2780, HCT116, HT29, WIL, CALU-3, MCF7, PC3 and HS852) with IC50 from 0.2-0.66 μM. PD101 shows low activity in A2780/cp70 and 2780AD cells, which are cisplatin and doxorubicin-resistant derivatives of A2780 cells. Belinostat could induce apoptosis through PARP cleavage and acetylation of histones H3/H4. Belinostat inhibits bladder cancer cell growth, especially in 5637 cells, which shows accumulation of G0-G1 phase, decrease in S phase and increase in G2-M phase. The growth inhibitory activity of belinostat on cell lines is not strongly influenced by the multidrug-resistant phenotype, whereas the activity of docetaxel is clearly affected. Belinostat could enhance the growth inhibitory activity of docetaxel or carboplatin in OVCAR-3 and A2780 cells. Belinostat also shows enhanced tubulin acetylation in ovarian cancer cell lines.in vivo: Belinostat also induces p21WAF1, HDAC core and cell communication genes in mouse bladder tumors. Belinostat monotherapy induces dose-proportional antitumor effects with TGI of 47% at a dose of 100mg/kg in A2780 xenograft. The combination of Belinostat (100 mg/kg) with carboplatin (40 mg/kg) could delay tumor growth from 18.6 days to 22.5 days.

Reference

[1]. Xiaozhong Qian et al. Activity of PXD101, a histone deacetylase inhibitor, in preclinical ovarian cancer studies Mol Cancer Ther August 2006 5; 2086
[2]. Nicola L. Steele et al. A Phase 1 Pharmacokinetic and Pharmacodynamic Study of the Histone Deacetylase Inhibitor Belinostat in Patients with Advanced Solid Tumors Clin Cancer Res February 1, 2008 14; 804
[3]. Dizon DS, Damstrup L, Finkler NJ, Lassen U, Celano P, Glasspool R, Crowley E, Lichenstein HS, Knoblach P, Penson RT.Phase II activity of belinostat (PXD-101), carboplatin, and paclitaxel in women with previously treated ovarian cancer.Int J Gynecol Cancer. 2012 Jul;22(6):979-86.
[4]. Gravina GL, Marampon F, Giusti I, Carosa E, Di Sante S, Ricevuto E, Dolo V, Tombolini V, Jannini EA, Festuccia C.Differential effects of PXD101 (belinostat) on androgen-dependent and androgen-independent prostate cancer models.Int J Oncol. 2012 Mar;40(3):711-20.
[5]. Cashen A, Juckett M, Jumonville A, Litzow M, Flynn PJ, Eckardt J, LaPlant B, Laumann K, Erlichman C, DiPersio J.Phase II study of the histone deacetylase inhibitor belinostat (PXD101) for the treatment of myelodysplastic syndrome (MDS).Ann Hematol. 2012 Jan;91(1):33-8. Epub 2011 May 3.