A4096-1ml | Belinostat (PXD101) [414864-00-9] Biotrend

Background

Belinostat (also known as PXD101) is a novel and potent hydroxamate-type inhibitor of histone deacetylase (HDAC) that inhibits the activity of HDAC in Hela cell extracts with 50% inhibition concentration IC₅₀ value of 27 nM. Belinostat has been found to significantly increase the acetylation of histones H3 and H4 and exerts cytotoxicity in a wide range of tumor cell lines. In the treatment of urothelial carcinoma cell lines, belinostat dose-dependently inhibits proliferation in 5637, T24, J82 and RT4 cells with IC₅₀ values of 1.0 μM, 3.5 μM, 6.0 μM and 10 μM respectively; while, in prostate cancer cell lines, it inhibits cancer cell growth with IC₅₀ values ranging from 0.5 to 2.5 μM.

Reference

Michael T Buckley, Joanne Yoon, Herman Yee, Luis Chiriboga, Leonard Liebes, Gulshan Ara, Xiaozhong Qian, Dean F Bajorin, Tung-Tien Sun, Xue-Ru Wu and Iman Osman. The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo. Journal of Translational Medicine 2007; 5:49

Giovanni Luca Gravina, Francesco Marampon, Ilaria Giusti, Eleonora Carosa, Stefania Di Sante, Enrico Ricevuto, Vincenza Dolo, Vincenzo Tombolini, Emmanuele A Jannini and Claudio Festuccia. Differential effects of PXD101 (belinostat) on androgen-dependent and androgen-independent prostate cancer models. International Journal of Oncology 40: 711-720, 2012

Plumb JA, Finn PW, Williams RJ, Bandara MJ, Romero MR, Watkins CJ, La Thangue NB, Brown R. Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101. Mol Cancer Ther. 2003 Aug;2(8):721-8.

Product Citation

1. Bagnall NH, Hines BM, et al. "Insecticidal activities of histone deacetylase inhibitors against a dipteran parasite of sheep, Lucilia cuprina." Int J Parasitol Drugs Drug Resist. 2017 Apr;7(1):51-60. PMID:28110187
2. Hai Y, Christianson DW. "Histone deacetylase 6 structure and molecular basis of catalysis and inhibition." Nat Chem Biol. 2016 Jul 25. PMID:27454933

Chemical Properties

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	318.35
Cas No.	414864-00-9
Formula	C₁₅H₁₄N₂O₄S
Synonyms	PXD-101, PXD 101, PX105684, PX-105684
Solubility	insoluble in H2O; ≥15.92 mg/mL in DMSO; ≥44.1 mg/mL in EtOH with ultrasonic
Chemical Name	(E)-N-hydroxy-3-[3-(phenylsulfamoyl)phenyl]prop-2-enamide
SDF	Download SDF
Canonical SMILES	C1=CC=C(C=C1)NS(=O)(=O)C2=CC=CC(=C2)C=CC(=O)NO
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Kinase experiment [1]:
Inhibitory activities	For activity assays, the reaction was carried out in a total volume of 150 μl of buffer [60 mM Tris (pH 7.4) containing 30% glycerol] containing 2 μl of cell extract and, where used, 2 μl of PXD101. The reaction was started by the addition of 2 μl of [3H]labeled substrate (acetylated histone H4 peptide corresponding to the 20 NH2-terminal residues). Samples were incubated at 37℃ for 45 min, and the reaction stopped by the addition of HCl and acetic acid (0.72 and 0.12 M final concentrations, respectively). Released [3H]acetate was extracted into 750 μl of ethyl acetate, and samples were centrifuged at 12,000×g for 5 min. The upper phase (600 μl) was transferred to 3 ml of scintillation fluid and counted.
Cell experiment [2]:
Cell lines	The human urinary bladder carcinoma cell lines 5637, T24, J82 and RT4.
Preparation method	Soluble in DMSO > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
Reaction Conditions	1-5 μM; 48 h.
Applications	In human urinary bladder carcinoma cell lines, belinostat (PXD101) inhibits cell proliferation in a dose dependent way with IC50 values of 1.0, 3.5, 6.0 and 10.0 μM in 5637, T24, J82 and RT4 cell lines, respectively. Belinostat (PXD101) (5 μM) decreases in cell growth and proliferation by 71%, 51%, 41% and 23% in 5637, T24, J82 and RT4 cell lines, respectively. Also, belinostat reduces cells in the S phase and increases cells in the G0-G1 phase.
Animal experiment [2]:
Animal models	UPII-Ha-ras transgenic mice.
Dosage form	100 mg/kg; 5 days each week for 3 weeks; intraperitoneal (IP) injections.
Preparation method	Dissolved in L-Arginine to give a final concentration of 20 mg/ml.
Applications	In UPII-Ha-ras transgenic mice, belinostat reduces the weights of Ras-expressing bladders of the male and female transgenic mice by 50% and 36%, respectively. Belinostat inhibits progression of bladder disease. Belinostat shows no detectable toxicity as evaluated by weight.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1]. Plumb JA, Finn PW, Williams RJ, et al. Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101. Mol Cancer Ther, 2003, 2(8): 721-728. [2]. Buckley MT, Yoon J, Yee H, et al. The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo. J Transl Med, 2007, 5: 49.