Details of the Drug

General Information of Drug (ID: DM6OC53)

Drug Name

PDX-101

Synonyms

Belinostat; 414864-00-9; PXD101; PXD-101; Belinostat (PXD101); Beleodaq; 866323-14-0; (E)-N-hydroxy-3-(3-(N-phenylsulfamoyl)phenyl)acrylamide; PXD 101; N-HYDROXY-3-(3-PHENYLSULFAMOYLPHENYL)ACRYLAMIDE; UNII-F4H96P17NZ; Belinostat(Random Configuration); NSC726630; PX105684; PX 105684; F4H96P17NZ; CHEBI:61076; (2E)-N-hydroxy-3-[3-(phenylsulfamoyl)phenyl]prop-2-enamide; N-HYDROXY-3-[3-[(PHENYLAMINO)SULFONYL]PHENYL]-2-PROPENAMIDE; (E)-N-hydroxy-3-[3-(phenylsulfamoyl)phenyl]prop-2-enamide; PX-105684

Indication

Disease Entry	ICD 11	Status	REF
Plasma cell myeloma	2A83.1	Approved	[1]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	N.A.	Approved	[1]
Primary cutaneous T-cell lymphoma	N.A.	Approved	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[2]
Haematological malignancy	2B33.Y	Phase 1	[3]
Peripheral T-cell lymphoma	2A90.C	Phase 1	[3]


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Therapeutic Class

Anticancer Agents

Affected Organisms

Humans and other mammals

ATC Code

L01XH04: PDX-101

L01XH: Histone deacetylase (HDAC) inhibitors

L01X: OTHER ANTINEOPLASTIC AGENTS

L01: ANTINEOPLASTIC AGENTS

L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

318.3

Logarithm of the Partition Coefficient (xlogp)

1.7

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Clearance: The clearance of drug is 1240 mL/min []
Half-life: The concentration or amount of drug in body reduced by one-half in 1.1 hours [4]
Metabolism: The drug is metabolized via the hepatic UGT1A1 []
Unbound Fraction: The unbound fraction of drug in plasma is 0.06% [4]
Vd: The volume of distribution (Vd) of drug is 409 +/- 76.7 L []

Chemical Identifiers

Formula: C15H14N2O4S
IUPAC Name: (E)-N-hydroxy-3-[3-(phenylsulfamoyl)phenyl]prop-2-enamide
Canonical SMILES: C1=CC=C(C=C1)NS(=O)(=O)C2=CC=CC(=C2)/C=C/C(=O)NO
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

Cross-matching ID

PubChem CID: 6918638
ChEBI ID: CHEMBL408513
CAS Number: 866323-14-0
UNII: F4H96P17NZ
DrugBank ID: DB05015
TTD ID: D0XT6W
VARIDT ID: DR00787
INTEDE ID: DR0184
ACDINA ID: D00866

Drug-Molecule Activity Atlas (DMA)^NEW

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Drug Pharmacogenomic Perturbation (DPP)^NEW

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Drug ADMET Endpoint Profile (DAE)^NEW

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Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Histone deacetylase (HDAC)	TTBH0VX	NOUNIPROTAC	Modulator	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[6]
UDP-glucuronosyltransferase 1A1 (UGT1A1)_{Main DME}	DEYGVN4	UD11_HUMAN	Substrate	[7]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
1,4-alpha-glucan-branching enzyme (GBE1)	OTK2N05B	GLGB_HUMAN	Gene/Protein Processing	[8]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 (PLCE1)	OTJISZOX	PLCE1_HUMAN	Gene/Protein Processing	[8]
15-hydroxyprostaglandin dehydrogenase (HPGD)	OTYZI6JB	PGDH_HUMAN	Gene/Protein Processing	[9]
2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial (GCAT)	OT6WZPWV	KBL_HUMAN	Gene/Protein Processing	[8]
2-hydroxyacylsphingosine 1-beta-galactosyltransferase	OT17ST61	CGT_HUMAN	Gene/Protein Processing	[9]
24-hydroxycholesterol 7-alpha-hydroxylase (CYP39A1)	OTBAJT4I	CP39A_HUMAN	Gene/Protein Processing	[8]
4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase 9 (FUT9)	OTLIJBQY	FUT9_HUMAN	Gene/Protein Processing	[8]
4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL)	OTW7D1SV	HPDL_HUMAN	Gene/Protein Processing	[9]
5-formyltetrahydrofolate cyclo-ligase (MTHFS)	OTZ39JNR	MTHFS_HUMAN	Gene/Protein Processing	[8]
A disintegrin and metalloproteinase with thrombospondin motifs 3 (ADAMTS3)	OT2U6VF5	ATS3_HUMAN	Gene/Protein Processing	[8]

Molecular Interaction Atlas (MIA)

MIA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as PDX-101

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of PDX-101 and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[10]

Coadministration of a Drug Treating the Disease Different from PDX-101 (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of PDX-101 and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[11]
Arn-509	DMT81LZ	Moderate	Increased metabolism of PDX-101 caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[10]
Gilteritinib	DMTI0ZO	Moderate	Decreased clearance of PDX-101 due to the transporter inhibition by Gilteritinib.	Acute myeloid leukaemia [2A60]	[11]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of PDX-101 and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[12]
Erdafitinib	DMI782S	Moderate	Decreased clearance of PDX-101 due to the transporter inhibition by Erdafitinib.	Bladder cancer [2C94]	[13]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of PDX-101 and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[14]
Tucatinib	DMBESUA	Moderate	Decreased metabolism of PDX-101 caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[15]
Alpelisib	DMEXMYK	Moderate	Increased metabolism of PDX-101 caused by Alpelisib mediated induction of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[16]
Regorafenib	DMHSY1I	Moderate	Decreased metabolism of PDX-101 caused by Regorafenib mediated inhibition of UGT.	Colorectal cancer [2B91]	[17]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of PDX-101 and Cannabidiol.	Epileptic encephalopathy [8A62]	[10]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of PDX-101 and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[18]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of PDX-101 and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[19]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of PDX-101 and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[20]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of PDX-101 and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[21]
Denosumab	DMNI0KO	Moderate	Additive myelosuppressive effects by the combination of PDX-101 and Denosumab.	Low bone mass disorder [FB83]	[22]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of PDX-101 caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[11]
Capmatinib	DMYCXKL	Moderate	Decreased clearance of PDX-101 due to the transporter inhibition by Capmatinib.	Lung cancer [2C25]	[23]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of PDX-101 and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[24]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of PDX-101 and Idelalisib.	Mature B-cell leukaemia [2A82]	[25]
Lasmiditan	DMXLVDT	Moderate	Decreased clearance of PDX-101 due to the transporter inhibition by Lasmiditan.	Migraine [8A80]	[26]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of PDX-101 and Tecfidera.	Multiple sclerosis [8A40]	[27]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of PDX-101 and Siponimod.	Multiple sclerosis [8A40]	[11]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of PDX-101 and Fingolimod.	Multiple sclerosis [8A40]	[28]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of PDX-101 and Ocrelizumab.	Multiple sclerosis [8A40]	[29]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of PDX-101 and Ozanimod.	Multiple sclerosis [8A40]	[10]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of PDX-101 caused by Rucaparib mediated inhibition of UGT.	Ovarian cancer [2C73]	[17]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of PDX-101 caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[30]
Lefamulin	DME6G97	Moderate	Decreased metabolism of PDX-101 caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[31]
Enzalutamide	DMGL19D	Moderate	Increased metabolism of PDX-101 caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[32]
Canakinumab	DM8HLO5	Moderate	Additive immunosuppressive effects by the combination of PDX-101 and Canakinumab.	Rheumatoid arthritis [FA20]	[33]
Rilonacept	DMGLUQS	Moderate	Additive immunosuppressive effects by the combination of PDX-101 and Rilonacept.	Rheumatoid arthritis [FA20]	[33]
Golimumab	DMHZV7X	Major	Additive immunosuppressive effects by the combination of PDX-101 and Golimumab.	Rheumatoid arthritis [FA20]	[34]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of PDX-101 when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[35]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of PDX-101 caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[36]


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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Arginine	E00112	6322	Buffering agent; Dispersing agent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Belinostat 500mg/vial powder	500mg/vial	Powder	Intravenous

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References

1	Belinostat FDA Label
2	A Phase II trial of Belinostat (PXD101) in patients with relapsed or refractory peripheral or cutaneous T-cell lymphoma. Br J Haematol. 2015 Mar;168(6):811-9.
3	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
6	Glucuronidation by UGT1A1 is the dominant pathway of the metabolic disposition of belinostat in liver cancer patients. PLoS One. 2013;8(1):e54522.
7	Effects of UGT1A1 genotype on the pharmacokinetics, pharmacodynamics, and toxicities of belinostat administered by 48-hour continuous infusion in patients with cancer. J Clin Pharmacol. 2016 Apr;56(4):461-73.
8	Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
9	A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
10	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
11	Cerner Multum, Inc. "Australian Product Information.".
12	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
13	Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
14	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
15	Product Information. Tukysa (tucatinib). Seattle Genetics Inc, Bothell, WA.
16	Product Information. Piqray (alpelisib). Novartis Pharmaceuticals, East Hanover, NJ.
17	Product Information. Beleodaq (belinostat). Spectrum Pharmaceuticals Inc, Irvine, CA.
18	Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
19	Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
20	Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
21	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
22	Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
23	Product Information. Tabrecta (capmatinib). Novartis Pharmaceuticals, East Hanover, NJ.
24	Bodmer M, Sulz M, Stadlmann S, Droll A, Terracciano L, Krahenbuhl S "Fatal liver failure in an adult patient with acute lymphoblastic leukemia following treatment with L-asparaginase." Digestion 74 (2006): epub. [PMID: 16988508]
25	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
26	Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
27	Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
28	Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
29	Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
30	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
31	Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
32	Benoist G, van Oort I, et al "Drug-drug interaction potential in men treated with enzalutamide: Mind the gap." Br J Clin Pharmacol 0 (2017): epub. [PMID: 28881501]
33	Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
34	Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
35	CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]
36	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.