| Identification | Back Directory | [Name]
PXD-101 | [CAS]
866323-14-0 | [Synonyms]
Belista
Belinostat（E）
PXD101;PX105684;PXD-101;PXD 101;PX-105684
(2E)-N-Hydroxy-3-[3-[(phenylamino)sulfonyl]phenyl]-2-propenamide
2-PropenaMide, N-hydroxy-3-[3-[(phenylaMino)sulfonyl]phenyl]-, (2E)- | [Molecular Formula]
C15H14N2O4S | [MOL File]
866323-14-0.mol | [Molecular Weight]
318.348 |
| Chemical Properties | Back Directory | [Melting point ]
172 °C(Solv: ethyl acetate (141-78-6)) | [density ]
1.427±0.06 g/cm3(Predicted) | [storage temp. ]
Sealed in dry,Room Temperature | [solubility ]
DMSO:64.0(Max Conc. mg/mL);201.4(Max Conc. mM) | [form ]
powder to crystal | [pka]
8.27±0.10(Predicted) | [color ]
White to Light yellow to Light orange | [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]
C(NO)(=O)/C=C/C1=CC=CC(S(NC2=CC=CC=C2)(=O)=O)=C1 |
| Hazard Information | Back Directory | [Uses]
Belinostat (PXD101; PX105684) is a potent HDAC inhibitor with an IC50 of 27 nM in HeLa cell extracts. | [Definition]
ChEBI: Belinostat is a hydroxamic acid-type histone deacetylase (HDAC) inhibitor with antineoplastic activity. It has a role as an antineoplastic agent and an EC 3.5.1.98 (histone deacetylase) inhibitor. It is a hydroxamic acid, a sulfonamide and an olefinic compound. | [Biological Activity]
Belinost at (PX105684; PXD101) is a potenthydroxamate class pan-selective histone deacetylases (HDACs) inhibitor (IC50: class I HDAC1/2/3/8 = 41/125/30/216 nMclass IIA HDAC4/7/9 = 115/67/128 nMclass IIB HDAC6 = 82 nM) with anti-cancer efficacy in vitro and in vivo. | [Enzyme inhibitor]
This synthetic epigenetic modulator (FW = 318.35 g/mol; CAS 866323-14-
0), also known as PXD101 and the IUPAC name, (2E) -N-hydroxy-3-[3-
(phenylsulfamoyl) phenyl]prop-2-enamide, inhibits histone deacetylase (IC50
= 27 nM) and induces a concentration-dependent increase (over the 0.2–5
μM range) in histone H4 acetylation and alters expression of genes located
on DNA associated with its parent histone octamer. A simple and
sensitive high-performance liquid chromatography ultraviolet method has
been developed for the quantification of PXD101 in human plasma. In
Rhesus monkeys, belinostat is cleared rapidly from plasma with a half-life
of 1.0 h, a mean residence time of 0.47 h, and a clearance of 425 mL/min/m2
. CSF drug exposure is <1% of plasma drug exposure and <10% of free
(non-protein bound) plasma drug exposure. The DNA-methylation inhibitor
decitabine and histone-deacetylase inhibitor belinostat increases the efficacy
of chemotherapeutic agents in tumors that acquired drug resistance due to
DNA methylation and gene silencing. | [in vivo]
Treatment of nude mice bearing human ovarian and colon tumor xenografts with Belinostat (10-40 mg/kg/day i.p.) daily for 7 days causes a significant dose-dependent growth delay with no obvious signs of toxicity to the mice. Growth delay is also observed for xenografts of cisplatin-resistant ovarian tumor cells. A marked increase in acetylation of H4 is detected in blood and tumor of mice 3 h after treatment with Belinostat (PXD101). The inhibition of growth of human tumor xenografts in mice, with no apparent toxicity[1]. Belinostat (PXD101) displays single-agent antitumor activity on human A2780 ovarian cancer s.c. xenografts which is enhanced via combination therapy with Carboplatin[2]. | [IC 50]
HDAC6: 82 nM (IC50); HDAC: 27 nM (IC50, Hela cell) | [References]
[1] Plumb JA, et al. Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histonedeacetylase inhibitor PXD101. Mol Cancer Ther. 2003 Aug;2(8):721-8. PMID:12939461
[2] Qian X, et al. Activity of PXD101, a histone deacetylase inhibitor, in preclinical ovarian cancer studies. Mol Cancer Ther. 2006 Aug;5(8):2086-95. DOI:10.1158/1535-7163.MCT-06-0111
[3] Chia S, et al. Phenotype-driven precision oncology as a guide for clinical decisions one patient at a time. Nat Commun. 2017 Sep 5;8(1):435. DOI:10.1038/s41467-017-00451-5 |
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