Belinostat

Belinostat (trade name Beleodaq, previously known as PXD101) is a histone deacetylase inhibitor drug developed by TopoTarget for the treatment of hematological malignancies and solid tumors.^[2]

Belinostat

Clinical data
Trade names	Beleodaq
Other names	PXD101
AHFS/Drugs.com	beleodaq
Routes of administration	Intravenous (IV)
ATC code	L01XH04 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Bioavailability	100% (IV)
Protein binding	92.9–95.8%[1]
Metabolism	UGT1A1
Excretion	Urine
Identifiers
IUPAC name (2E)-N-Hydroxy-3-[3-(phenylsulfamoyl)phenyl]prop-2-enamide
CAS Number	866323-14-0 N
PubChem CID	6918638
DrugBank	DB05015
ChemSpider	5293831 Y
UNII	F4H96P17NZ
KEGG	D08870
ChEBI	CHEBI:61076 Y
ChEMBL	ChEMBL408513 Y
CompTox Dashboard (EPA)	DTXSID60194378
Chemical and physical data
Formula	C15H14N2O4S
Molar mass	318.35 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=S(=O)(Nc1ccccc1)c2cc(\C=C\C(=O)NO)ccc2
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+ Y Key:NCNRHFGMJRPRSK-MDZDMXLPSA-N Y

It was approved in July 2014 by the US FDA to treat peripheral T-cell lymphoma.^[3]

In 2007 preliminary results were released from the Phase II clinical trial of intravenous belinostat in combination with carboplatin and paclitaxel for relapsed ovarian cancer.^[4] Final results in late 2009 of a phase II trial for T-cell lymphoma were encouraging.^[5] Belinostat has been granted orphan drug and fast track designation by the FDA,^[6] and was approved in the US for the use against peripheral T-cell lymphoma on 3 July 2014.^[3] It is not approved in Europe as of August 2014^[update].^[7]

The approved pharmaceutical formulation is given intravenously.^[8]: 180 Belinostat is primarily metabolized by UGT1A1; the initial dose should be reduced if the recipient is known to be homozygous for the UGT1A1*28 allele.^{[8]: 179 and 181}

References

1. "Beleodaq (belinostat) For Injection, For Intravenous Administration. Full Prescribing Information" (PDF). Spectrum Pharmaceuticals, Inc. Irvine, CA 92618. Archived from the original (PDF) on 4 March 2016. Retrieved 21 November 2015.
2. Plumb JA, Finn PW, Williams RJ, Bandara MJ, Romero MR, Watkins CJ, et al. (August 2003). "Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101". Molecular Cancer Therapeutics. 2 (8): 721–8. PMID 12939461.
3. "FDA approves Beleodaq to treat rare, aggressive form of non-Hodgkin lymphoma". FDA. 3 July 2014.
4. "CuraGen Corporation (CRGN) and TopoTarget A/S Announce Presentation of Belinostat Clinical Trial Results at AACR-NCI-EORTC International Conference". October 2007. Archived from the original on 2011-07-16. Retrieved 2011-12-06.
5. Final Results of a Phase II Trial of Belinostat (PXD101) in Patients with Recurrent or Refractory Peripheral or Cutaneous T-Cell Lymphoma, December 2009
6. Carroll J (2 February 2010). "Spectrum adds to cancer pipeline with $350M deal". Fierce Biotech.
7. Spreitzer H (4 August 2014). "Neue Wirkstoffe – Belinostat". Österreichische Apothekerzeitung (in German) (16/2014): 27.
8. Bragalone DL, American Pharmacists Association, Lexi-Comp, Inc. (2016). Drug Information Handbook for Oncology (14th ed.). Wolters Kluwer. ISBN 9781591953517.