BELINOSTAT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C15H14N2O4S
Molecular Weight	318.348
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

ONC(=O)\C=C\C1=CC=CC(=C1)S(=O)(=O)NC2=CC=CC=C2

InChI

InChIKey=NCNRHFGMJRPRSK-MDZDMXLPSA-N

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+

HIDE SMILES / InChI

Molecular Formula	C15H14N2O4S
Molecular Weight	318.348
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206256lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/?term=16928830; http://www.ncbi.nlm.nih.gov/pubmed/?term=24800886; http://www.ncbi.nlm.nih.gov/pubmed/?term=23382909

Belinostat is a hydroxamate-type histone deacetylase inhibitor indicated for the treatment of relapsed or refractory peripheal T-cell lymphoma. The compound received orphan drug designation for the treatment of malignant thymomas. Acting on a histone deacetylase Belinostat causes the accumulation of acetylated histones and other proteins, inducing cell cycle arrest and/or apoptosis of some transformed cells. Belinostat targets HDAC enzymes, thereby inhibiting tumor cell proliferation, inducing apoptosis, promoting cellular differentiation, and inhibiting angiogenesis. This agent may sensitize drug-resistant tumor cells to other antineoplastic agents, possibly through a mechanism involving the down-regulation of thymidylate synthase. PXD101 has been shown in preclinical studies to have the potential to treat a wide range of solid and hematologic malignancies either as a monotherapy or in combination with other active agents, and both an oral and intravenous formulation of the drug are being evaluated in clinical trials.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histone deacetylase 3 35 Target ID: O15379 Gene ID: 8841.0 Gene Symbol: HDAC3 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=18789133	Inhibitor 8504		41.0 nM [EC50]
Histone deacetylase 1 51 Target ID: Q13547 Gene ID: 3065.0 Gene Symbol: HDAC1 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=18789133	Inhibitor 8504		30.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Lymphoma, T-cell, peripheral 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206256lbl.pdf	Primary		Approved 8583	BELEODAQ Approved Use Indicated for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). This indication is approved under accelerated approval based on tumor response rate and duration of response. Launch Date 2014

C_max

Value	Dose	Analyte	Population
1.68 ug/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01273155	400 mg/m^2 single, intravenous dose: 400 mg/m^2 route of administration: intravenous experiment type: single co-administered:	BELINOSTAT ACID plasma	Homo sapiens population: unhealthy age: adults sex: food status:
2.1 ug/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01273155	400 mg/m^2 single, intravenous dose: 400 mg/m^2 route of administration: intravenous experiment type: single co-administered:	METHYL BELINOSTAT plasma	Homo sapiens population: unhealthy age: adults sex: food status:
681 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/20706839	1000 mg/m² 1 times / day multiple, oral dose: 1000 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:	BELINOSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
21.9 ug/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01273155	400 mg/m^2 single, intravenous dose: 400 mg/m^2 route of administration: intravenous experiment type: single co-administered:	BELINOSTAT plasma	Homo sapiens population: unhealthy age: adults sex: food status:
80.8 ug/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01273155	400 mg/m^2 single, intravenous dose: 400 mg/m^2 route of administration: intravenous experiment type: single co-administered:	BELINOSTAT GLUCURONIDE plasma	Homo sapiens population: unhealthy age: adults sex: food status:
1.26 ug/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01273155	400 mg/m^2 single, intravenous dose: 400 mg/m^2 route of administration: intravenous experiment type: single co-administered:	BELINOSTAT AMIDE plasma	Homo sapiens population: unhealthy age: adults sex: food status:
2.56 ug/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01273155	400 mg/m^2 single, intravenous dose: 400 mg/m^2 route of administration: intravenous experiment type: single co-administered:	3-(PHENYLSULFAMOYL)BENZOIC ACID plasma	Homo sapiens population: unhealthy age: adults sex: food status:

AUC

Value	Dose	Analyte	Population
361 ug*min/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01273155	400 mg/m^2 single, intravenous dose: 400 mg/m^2 route of administration: intravenous experiment type: single co-administered:	BELINOSTAT ACID plasma	Homo sapiens population: unhealthy age: adults sex: food status:
354 ug*min/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01273155	400 mg/m^2 single, intravenous dose: 400 mg/m^2 route of administration: intravenous experiment type: single co-administered:	METHYL BELINOSTAT plasma	Homo sapiens population: unhealthy age: adults sex: food status:
8.7 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/20706839	1000 mg/m² 1 times / day multiple, oral dose: 1000 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:	BELINOSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
719 ug*min/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01273155	400 mg/m^2 single, intravenous dose: 400 mg/m^2 route of administration: intravenous experiment type: single co-administered:	BELINOSTAT plasma	Homo sapiens population: unhealthy age: adults sex: food status:
15.1 mg*min/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01273155	400 mg/m^2 single, intravenous dose: 400 mg/m^2 route of administration: intravenous experiment type: single co-administered:	BELINOSTAT GLUCURONIDE plasma	Homo sapiens population: unhealthy age: adults sex: food status:
647 ug*min/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01273155	400 mg/m^2 single, intravenous dose: 400 mg/m^2 route of administration: intravenous experiment type: single co-administered:	BELINOSTAT AMIDE plasma	Homo sapiens population: unhealthy age: adults sex: food status:
1009 ug*min/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01273155	400 mg/m^2 single, intravenous dose: 400 mg/m^2 route of administration: intravenous experiment type: single co-administered:	3-(PHENYLSULFAMOYL)BENZOIC ACID plasma	Homo sapiens population: unhealthy age: adults sex: food status:

T_1/2

Value	Dose	Analyte	Population
131 min Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01273155	400 mg/m^2 single, intravenous dose: 400 mg/m^2 route of administration: intravenous experiment type: single co-administered:	BELINOSTAT ACID plasma	Homo sapiens population: unhealthy age: adults sex: food status:
79.6 min Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01273155	400 mg/m^2 single, intravenous dose: 400 mg/m^2 route of administration: intravenous experiment type: single co-administered:	METHYL BELINOSTAT plasma	Homo sapiens population: unhealthy age: adults sex: food status:
1.5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/20706839	1000 mg/m² 1 times / day multiple, oral dose: 1000 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:	BELINOSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
118 min Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01273155	400 mg/m^2 single, intravenous dose: 400 mg/m^2 route of administration: intravenous experiment type: single co-administered:	BELINOSTAT plasma	Homo sapiens population: unhealthy age: adults sex: food status:
280 min Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01273155	400 mg/m^2 single, intravenous dose: 400 mg/m^2 route of administration: intravenous experiment type: single co-administered:	BELINOSTAT GLUCURONIDE plasma	Homo sapiens population: unhealthy age: adults sex: food status:
305 min Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01273155	400 mg/m^2 single, intravenous dose: 400 mg/m^2 route of administration: intravenous experiment type: single co-administered:	BELINOSTAT AMIDE plasma	Homo sapiens population: unhealthy age: adults sex: food status:
264 min Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01273155	400 mg/m^2 single, intravenous dose: 400 mg/m^2 route of administration: intravenous experiment type: single co-administered:	3-(PHENYLSULFAMOYL)BENZOIC ACID plasma	Homo sapiens population: unhealthy age: adults sex: food status:

F_unbound

Value	Dose	Co-administered	Analyte	Population
5.65% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206256lbl.pdf			BELINOSTAT plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
1200 mg/m2 1 times / day steady, intravenous Highest studied dose Dose: 1200 mg/m2, 1 times / day Route: intravenous Route: steady Dose: 1200 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18245542	unhealthy, 58.5 years (range: 25-74 years) Health Status: unhealthy Age Group: 58.5 years (range: 25-74 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18245542	DLT: Atrial fibrillation, Diarrhea... Other AEs: Nausea, Vomiting... Dose limiting toxicities: Atrial fibrillation (1 patient) Diarrhea (1 patient) Fatigue (grade 3, 2 patients) Other AEs: Nausea (grade 2, 1 patient) Vomiting (grade 2, 1 patient) Lethargy (grade 3, 1 patient) Diarrhea (grade 3, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/18245542
1000 mg/m2 1 times / day steady, intravenous Recommended\|MTD Dose: 1000 mg/m2, 1 times / day Route: intravenous Route: steady Dose: 1000 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18245542	unhealthy, 58.5 years (range: 25-74 years) Health Status: unhealthy Age Group: 58.5 years (range: 25-74 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18245542	DLT: Atrial fibrillation, Vomiting... Dose limiting toxicities: Atrial fibrillation (1 patient) Vomiting (1 patient) Nausea (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/18245542
600 mg/m2 1 times / day steady, intravenous Dose: 600 mg/m2, 1 times / day Route: intravenous Route: steady Dose: 600 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18245542	unhealthy, 58.5 years (range: 25-74 years) Health Status: unhealthy Age Group: 58.5 years (range: 25-74 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18245542	DLT: Fatigue... Dose limiting toxicities: Fatigue (grade 3) Sources: https://pubmed.ncbi.nlm.nih.gov/18245542
1000 mg/m2 1 times / day steady, intravenous Recommended\|MTD Dose: 1000 mg/m2, 1 times / day Route: intravenous Route: steady Dose: 1000 mg/m2, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206256lbl.pdf	unhealthy, 64.0 years (range: 29-81 years) Health Status: unhealthy Age Group: 64.0 years (range: 29-81 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206256lbl.pdf	Disc. AE: Fatigue, Anemia... Other AEs: Nausea, Nausea... AEs leading to discontinuation/dose reduction: Fatigue (grade 3-4, 5%) Anemia (grade 3-4, 11%) Febrile neutropenia Other AEs: Nausea (grade 1-2, 41%) Nausea (grade 3-4, 1%) Fatigue (grade 1-2, 32%) Pyrexia (grade 1-2, 33%) Pyrexia (grade 3-4, 2%) Anemia (grade 1-2, 21%) Vomiting (grade 1-2, 28%) Vomiting (grade 3-4, 1%) Constipation (grade 1-2, 22%) Constipation (grade 3-4, 1%) Diarrhea (grade 1-2, 21%) Diarrhea (grade 3-4, 2%) Dyspnea (grade 1-2, 16%) Dyspnea (grade 3-4, 6%) Rash (grade 1-2, 19%) Rash (grade 3-4, 1%) Peripheral edema (grade 1-2, 20%) Cough (grade 1-2, 19%) Thrombocytopenia (grade 1-2, 9%) Thrombocytopenia (grade 3-4, 7%) Pruritus (grade 1-2, 13%) Pruritus (grade 3-4, 3%) Chills (grade 1-2, 15%) Chills (grade 3-4, 1%) Blood lactate dehydrogenase increased (grade 1-2, 14%) Blood lactate dehydrogenase increased (grade 3-4, 2%) Decreased appetite (grade 1-2, 13%) Decreased appetite (grade 3-4, 2%) Headache (grade 1-2, 15%) Infusion site pain (grade 1-2, 14%) Hypokalemia (grade 1-2, 8%) Hypokalemia (grade 3-4, 4%) QT prolonged (grade 1-2, 7%) QT prolonged (grade 3-4, 4%) Abdominal pain (grade 1-2, 10%) Abdominal pain (grade 3-4, 1%) Hypotension (grade 1-2, 7%) Hypotension (grade 3-4, 3%) Phlebitis (grade 1-2, 9%) Phlebitis (grade 3-4, 1%) Dizziness (grade 1-2, 10%) Tumor lysis syndrome (grade 4, 1 patient) Pneumonia (serious\|grade 5, > 2) Sepsis (serious\|grade 5, > 2) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206256lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inducer 1087	substrate 1193 inhibitor 2438 inducer 440		inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 1057	UGT1A1 479 CYP2A6 626 P-gp 2052	CYP1A2 832 CYP2B6 669 CYP2C19 329

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206256Orig1s000ClinPharmR.pdf#page=21 Page: 21.0	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206256Orig1s000ClinPharmR.pdf#page=23 Page: 23.0	no
CYP2C19 2141	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206256Orig1s000ClinPharmR.pdf#page=23 Page: 23.0	no
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206256Orig1s000ClinPharmR.pdf#page=23 Page: 23.0	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206256Orig1s000ClinPharmR.pdf#page=23 Page: 23.0	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206256Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	yes [IC50 100 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206256Orig1s000ClinPharmR.pdf#page=21 Page: 23.0	yes [IC50 49.1 uM]	3-ASBA 1
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206256Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	yes [IC50 61.8 uM]		no (co-administration study) Comment: A human PK study was conducted in patients following the administration of the CYP2C9 substrate warfarin in the absence and presence of belinostat. The exposure of S-warfarin was not increased to a meaningful extent. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206256Orig1s000ClinPharmR.pdf#page=7 Page: 7.0

Drug as victim

Target	Modality	Activity
CYP2A6 626	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206256Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	yes
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206256Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	yes
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206256Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	yes
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206256Orig1s000ClinPharmR.pdf#page=24 Page: 24.0	yes
UGT1A1 479	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206256Orig1s000ClinPharmR.pdf#page=7 Page: 7.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206256Orig1s000PharmR.pdf#page=12 Page: 12.0		3-ASBA 1

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:61076	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:61076
ChemicalBook	CB3260643	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3260643
ChemicalBook	CB82628305	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB82628305
eMolecules	28302879	https://www.emolecules.com/cgi-bin/more?vid=28302879
MolPort	MolPort-009-679-433	https://www.molport.com/shop/molecule-link/MolPort-009-679-433
Selleck Chemicals	Belinostat	http://www.selleckchem.com/products/Belinostat.html
ZINC	ZINC000003818726	http://zinc15.docking.org/substances/ZINC000003818726

PubMed

Title	Date	PubMed
A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors.	2015-09	26272509
Epigenetic and molecular mechanisms underlying the antileukemic activity of the histone deacetylase inhibitor belinostat in human acute promyelocytic leukemia cells.	2014-09	24800886
Histone acetylation-mediated regulation of the Hippo pathway.	2013	23671600
Glucuronidation by UGT1A1 is the dominant pathway of the metabolic disposition of belinostat in liver cancer patients.	2013	23382909
Optimization of the in vitro cardiac safety of hydroxamate-based histone deacetylase inhibitors.	2011-07-14	21650221
Chemical phylogenetics of histone deacetylases.	2010-03	20139990
Gene expression-signature of belinostat in cell lines is specific for histone deacetylase inhibitor treatment, with a corresponding signature in xenografts.	2009-09	19606018
Combined inhibition of DNA methylation and histone acetylation enhances gene re-expression and drug sensitivity in vivo.	2009-03-10	19259094
Integrative analysis of epigenetic modulation in melanoma cell response to decitabine: clinical implications.	2009	19234609
Interactions between bortezomib and romidepsin and belinostat in chronic lymphocytic leukemia cells.	2008-01-15	18223231
Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors.	2008-01-15	17868033
The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo.	2007-10-12	17935615
Activity of PXD101, a histone deacetylase inhibitor, in preclinical ovarian cancer studies.	2006-08	16928830
Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101.	2003-08	12939461

Patents

Sample Use Guides

In Vivo Use Guide

Recommended dosage of Beleodaq is 1,000 mg/m^2 administered over 30 minutes by intravenous infusion once daily on days 1-5 of a 21-day cycle. Cycles can be repeated until disease progression or unacceptable toxicity. Treatment discontinuation or interruption with or without dosage reductions by 25% may be needed to manage adverse reactions.

Route of Administration: Intravenous

In Vitro Use Guide

The in vitro treatment of carcinoma cell lines at 1–5 uM belinostat for 48 h caused a dose-dependent inhibition of proliferation, with the most potent inhibitory effect occurring on 5637 cells.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:02:19 GMT 2025` Edited by `admin` on `Mon Mar 31 18:02:19 GMT 2025`
Record UNII	F4H96P17NZ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BELINOSTAT

Official Name

English

BELEODAQ

Preferred Name

English

BELINOSTAT [VANDF]

Common Name

English

N-HYDROXY-3-(3-((PHENYLAMINO)SULFONYL)PHENYL)-2-PROPENAMIDE

Systematic Name

English

NSC-726630

Code

English

2-PROPENAMIDE, N-HYDROXY-3-(3-((PHENYLAMINO)SULFONYL)PHENYL)-, (2E)-

Systematic Name

English

PX-105684

Code

English

BELINOSTAT [USAN]

Common Name

English

BELINOSTAT [ORANGE BOOK]

Common Name

English

2-PROPENAMIDE, N-HYDROXY-3-(3-((PHENYLAMINO)SULFONYL)PHENYL)-

Systematic Name

English

PXD-101

Code

English

BELINOSTAT [MI]

Common Name

English

(2E)-N-HYDROXY-3-(3-(PHENYLSULFAMOYL)PHENYL)PROP-2-ENAMIDE

Systematic Name

English

Belinostat [WHO-DD]

Common Name

English

PXD101

Code

English

belinostat [INN]

Common Name

English

N-Hydroxy-3-[3-(phenylsulfamoyl)phenyl]prop-2-enamide

Systematic Name

English

Classification Tree Code System Code

NDF-RT

N0000175588