PANOBINOSTAT HYDRATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H23N3O2.H2O
Molecular Weight	367.4415
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.CC1=C(CCNCC2=CC=C(\C=C\C(=O)NO)C=C2)C3=C(N1)C=CC=C3

InChI

InChIKey=YUKVPQZUSANPNW-ASTDGNLGSA-N

InChI=1S/C21H23N3O2.H2O/c1-15-18(19-4-2-3-5-20(19)23-15)12-13-22-14-17-8-6-16(7-9-17)10-11-21(25)24-26;/h2-11,22-23,26H,12-14H2,1H3,(H,24,25);1H2/b11-10+;

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf
Curator's Comment: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB06603

Panobinostat is an oral deacetylace (DAC) inhibitor approved on February 23, 2015 by the FDA for the treatment of multiple myeloma. The approval was accelerated based on progression-free survival, therefore confirmatory trials by the sponsor to demonstrate clinical efficacy in multiple myeloma treatment are in progress of being conducted. Panobinostat is marketed by Novartis under the brand name Farydak. Panobinostat is a deacetylase (DAC) inhibitor. DACs, also known as histone DACs (HDAC), are responsible for regulating the acetylation of about 1750 proteins in the body; their functions are involved in many biological processes including DNA replication and repair, chromatin remodelling, transcription of genes, progression of the cell-cycle, protein degradation and cytoskeletal reorganization. In multiple myeloma, there is an overexpression of DAC proteins. Panobinostat inhibits class I (HDACs 1, 2, 3, 8), class II (HDACs 4, 5, 6, 7, 9, 10) and class IV (HDAC 11) proteins. Panobinostat's antitumor activity is believed to be attributed to epigenetic modulation of gene expression and inhibition of protein metabolism. Panobinostat also exhibits cytotoxic synergy with bortezomib, a proteasome inhibitor concurrently used in treatment of multiple myeloma.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Histone deacetylase 8 17 Target ID: CHEMBL3192 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22344701	Inhibitor 8297	280.0 nM [IC50]
Histone deacetylase 6 27 Target ID: CHEMBL1865 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22344701	Inhibitor 8297	11.0 nM [IC50]
Histone deacetylase 3 35 Target ID: CHEMBL1829 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22344701	Inhibitor 8297	2.1 nM [IC50]
Histone deacetylase 2 37 Target ID: CHEMBL1937 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22344701	Inhibitor 8297	13.0 nM [IC50]
Histone deacetylase 1 51 Target ID: CHEMBL325 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22344701	Inhibitor 8297	2.5 nM [IC50]
Histone deacetylase 4 11 Target ID: CHEMBL3524 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22344701	Inhibitor 8297	200.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Multiple myeloma 159 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf	Primary		Approved 8429	FARYDAK Approved Use FARYDAK, a histone deacetylase inhibitor, in combination with bortezomib and dexamethasone, is indicated for the treatment of patients with multiple myeloma who have received at least 2 prior regimens, including bortezomib and an immunomodulatory agent Launch Date 2015

C_max

Value	Dose	Co-administered	Analyte	Population
15.3 ng/mL REVIEW https://www.ncbi.nlm.nih.gov/pubmed/27226420	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered: BORTEZOMIB	BORTEZOMIB	PANOBINOSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
95.2 ng × h/mL REVIEW https://www.ncbi.nlm.nih.gov/pubmed/27226420	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered: BORTEZOMIB	BORTEZOMIB	PANOBINOSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
16.7 h REVIEW https://www.ncbi.nlm.nih.gov/pubmed/27226420	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered: BORTEZOMIB	BORTEZOMIB	PANOBINOSTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf			PANOBINOSTAT plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
34 mg/m2 3 times / week multiple, oral Highest studied dose\|RP2D Dose: 34 mg/m2, 3 times / week Route: oral Route: multiple Dose: 34 mg/m2, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/32338562	unhealthy, 1-21 years n = 11 Health Status: unhealthy Condition: relapsed and refractory hematologic malignancies Age Group: 1-21 years Sex: M+F Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/32338562	DLT: Hypertriglyceridemia... Dose limiting toxicities: Hypertriglyceridemia (grade 4, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/32338562
15 mg/m2 1 times / week multiple, intravenous (starting) Dose: 15 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 15 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/29987369	unhealthy, 3-17 years n = 9 Health Status: unhealthy Condition: refractory solid tumors Age Group: 3-17 years Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/29987369	DLT: Electrocardiogram T wave abnormal... Dose limiting toxicities: Electrocardiogram T wave abnormal (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/29987369
20 mg 3 times / week multiple, oral Recommended\|MTD Dose: 20 mg, 3 times / week Route: oral Route: multiple Dose: 20 mg, 3 times / week Co-administed with:: bortezomib(1.3 mg/m2) dexamethasone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf Page: p. 36, 45	unhealthy, 60 years (range: 28-79 years) n = 386 Health Status: unhealthy Age Group: 60 years (range: 28-79 years) Sex: M+F Population Size: 386 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf Page: p. 36, 45	Disc. AE: Diarrhea, Thrombocytopenia... AEs leading to discontinuation/dose reduction: Diarrhea (17 patients) Thrombocytopenia (6 patients) Fatigue (11 patient) Asthenia (11 patient) Peripheral neuropathy (14 patients) Thrombocytopenia (28%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf Page: p. 36, 45
20 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21964801	unhealthy, 63.0 years (range: 43–75 years) n = 8 Health Status: unhealthy Condition: advanced solid tumors Age Group: 63.0 years (range: 43–75 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/21964801	DLT: Gamma glutamyl transpeptidase increased... Other AEs: Thrombocytopenia, Leukopenia... Dose limiting toxicities: Gamma glutamyl transpeptidase increased (grade 3, 1 patient) Other AEs: Thrombocytopenia (grade 3-4, 2 patients) Leukopenia (grade 3-4, 2 patients) Neutropenia (grade 3-4, 5 patients) Nausea (grade 1-2, 4 patients) Stomatitis (grade 1-2, 3 patients) Vomiting (grade 1-2, 3 patients) Fatigue (grade 3-4, 1 patient) Fever (grade 1-2, 4 patients) Decreased appetite (grade 1-2, 5 patients) Hypoalbuminemia (grade 1-2, 2 patients) Rash (grade 1-2, 3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/21964801
20 mg 3 times / week multiple, oral Recommended\|MTD Dose: 20 mg, 3 times / week Route: oral Route: multiple Dose: 20 mg, 3 times / week Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf	Other AEs: Diarrhea, Arrhythmia... Other AEs: Diarrhea (severe\|grade 5, 25%) Arrhythmia (severe) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587 inducer 781	inducer 389 inhibitor 1767	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP3A4/5 278 CYP2C19 1478 CYP1A2 1524 CYP2C8 911 CYP2E1 882 OAT1 599 OATP1B1 788 OATP1B3 706 OAT3 642 OCT1 512 OCT2 647 BCRP 699	CYP2C19 991 UGT1A1 418 UGT1A3 422 UGT1A7 236 UGT1A8 283 UGT1A9 380 UGT2B4 249 P-gp 1537 OCT1 327 OAT2 115	CYP1A1 108 CYP1A2 701 CYP2B6 547 CYP2C8 168 CYP2C19 293 CYP3A5 76 UGT1A1 69 P-gp 257 MRP2 111

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=59 Page: 59.0	no [IC50 >100 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=59 Page: 59.0	no [IC50 >100 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=59 Page: 59.0	no [IC50 >100 uM]
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=59 Page: 59.0	no [IC50 >100 uM]
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	no
CYP1A1 218	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=59 Page: 59.0	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=59 Page: 59.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=59 Page: 59.0	no
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=59 Page: 59.0	no
CYP2C8 965	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=59 Page: 59.0	no
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=59 Page: 59.0	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=59 Page: 59.0	no
CYP3A5 130	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=59 Page: 59.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	no
MRP2 475	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	unlikely
P-gp 1650	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	unlikely
UGT1A1 254	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	unlikely
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=59 Page: 59.0	weak
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	weak
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=59 Page: 59.0	weak
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=28 Page: 28.0	yes [IC50 2 uM]	yes (co-administration study) Comment: The coadministration of a single 60 mg dextromethorphan (DM) dose with FARYDAK (20 mg once per day, on Days 3, 5, and 8) increased the Cmax and AUC0-¥ of DM by 20% to 200% (interquartile range)and 20% to 130% (interquartile range), respectively Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=28 Page: 28.0
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	yes
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	yes
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	yes
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	yes
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=27 Page: 27.0	major	yes (co-administration study) Comment: In an in vivo evaluation, coadministration of a single 20 mg FARYDAK dose with the strong CYP3A4 inhibitor ketoconazole (200 mg twice daily for 14 days) increased the Cmax and AUC0-48 of PAN by 67% and 73% respectively Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=27 Page: 27.0
OAT2 115	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	no
OCT1 327	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=62 Page: 62.0	yes [Km >100 uM]
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=27 Page: 27.0	yes
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=27 Page: 27.0	yes
UGT1A1 418	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=27 Page: 27.0	yes
UGT1A3 422	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=27 Page: 27.0	yes
UGT1A7 236	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=27 Page: 27.0	yes
UGT1A8 283	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=27 Page: 27.0	yes
UGT1A9 380	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=27 Page: 27.0	yes
UGT2B4 249	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf#page=27 Page: 27.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000PharmR.pdf#page=13 Page: 13.0
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000PharmR.pdf#page=13 Page: 13.0		BJB432 3

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:85990	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:85990
ChemicalBook	CB61009161	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB61009161
MolPort	MolPort-005-933-338	https://www.molport.com/shop/molecule-link/MolPort-005-933-338
Selleck Chemicals	LBH-589	http://www.selleckchem.com/products/LBH-589.html
ZINC	ZINC000022010649	http://zinc15.docking.org/substances/ZINC000022010649
eMolecules	26941323	https://www.emolecules.com/cgi-bin/more?vid=26941323

PubMed

Title	Date	PubMed
Targeting tumor angiogenesis with histone deacetylase inhibitors: the hydroxamic acid derivative LBH589.	2006 Jan 15	16428510
Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors.	2008 Jan 15	17868033
To selectivity and beyond.	2010 Dec	21139608
Discovery of (2E)-3-{2-butyl-1-[2-(diethylamino)ethyl]-1H-benzimidazol-5-yl}-N-hydroxyacrylamide (SB939), an orally active histone deacetylase inhibitor with a superior preclinical profile.	2011 Jul 14	21634430
Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells.	2014 May	24435446
The Bromodomain Inhibitor JQ1 and the Histone Deacetylase Inhibitor Panobinostat Synergistically Reduce N-Myc Expression and Induce Anticancer Effects.	2016 May 15	26733615

Patents

Sample Use Guides

In Vivo Use Guide

20 mg, taken orally once every other day for 3 doses per week (on Days 1, 3, 5, 8, 10, and 12) of Weeks 1 and 2 of each 21-day cycle for 8 cycles

Route of Administration: Oral

In Vitro Use Guide

Besides, Panobinostat inhibits growth of non small cell lung cancer cell lines (such as human H1299, L55 and A549 with IC50 of 5 nM, 11 nM and 30 nM, respectively), mesothelioma (such as human OK-6 and Ok-5 with IC50 of 5 nM and 7 nM, respectively) and small cell lung cancer cell lines (such as human RG-1 and LD-T with IC50 of 4 nM and 5 nM, respectively).

Name

Type

Language

PANOBINOSTAT HYDRATE

Common Name

English

LBH-589

Code

English

LBH589

Code

English

Code System Code Type Description

PUBCHEM

76972289

Created by admin on Fri Dec 15 16:23:32 GMT 2023 , Edited by admin on Fri Dec 15 16:23:32 GMT 2023

PRIMARY

FDA UNII

D07V79Q44T

Created by admin on Fri Dec 15 16:23:32 GMT 2023 , Edited by admin on Fri Dec 15 16:23:32 GMT 2023

PRIMARY

CHEBI

85990

Created by admin on Fri Dec 15 16:23:32 GMT 2023 , Edited by admin on Fri Dec 15 16:23:32 GMT 2023

PRIMARY

DRUG BANK

DBSALT001984

Created by admin on Fri Dec 15 16:23:32 GMT 2023 , Edited by admin on Fri Dec 15 16:23:32 GMT 2023

PRIMARY

ACTIVE MOIETY


					9647FM7Y3Z

PANOBINOSTAT

SUBSTANCE RECORD


					D07V79Q44T

PANOBINOSTAT HYDRATE

AE	Significance	Dose	Population
Hypertriglyceridemia	grade 4, 1 patient DLT	34 mg/m2 3 times / week multiple, oral Highest studied dose\|RP2D Dose: 34 mg/m2, 3 times / week Route: oral Route: multiple Dose: 34 mg/m2, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/32338562	unhealthy, 1-21 years n = 11 Health Status: unhealthy Condition: relapsed and refractory hematologic malignancies Age Group: 1-21 years Sex: M+F Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/32338562
Electrocardiogram T wave abnormal	2 patients DLT	15 mg/m2 1 times / week multiple, intravenous (starting) Dose: 15 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 15 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/29987369	unhealthy, 3-17 years n = 9 Health Status: unhealthy Condition: refractory solid tumors Age Group: 3-17 years Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/29987369
Asthenia	11 patient Disc. AE	20 mg 3 times / week multiple, oral Recommended\|MTD Dose: 20 mg, 3 times / week Route: oral Route: multiple Dose: 20 mg, 3 times / week Co-administed with:: bortezomib(1.3 mg/m2) dexamethasone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf Page: p. 36, 45	unhealthy, 60 years (range: 28-79 years) n = 386 Health Status: unhealthy Age Group: 60 years (range: 28-79 years) Sex: M+F Population Size: 386 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf Page: p. 36, 45
Fatigue	11 patient Disc. AE	20 mg 3 times / week multiple, oral Recommended\|MTD Dose: 20 mg, 3 times / week Route: oral Route: multiple Dose: 20 mg, 3 times / week Co-administed with:: bortezomib(1.3 mg/m2) dexamethasone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf Page: p. 36, 45	unhealthy, 60 years (range: 28-79 years) n = 386 Health Status: unhealthy Age Group: 60 years (range: 28-79 years) Sex: M+F Population Size: 386 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf Page: p. 36, 45
Peripheral neuropathy	14 patients Disc. AE	20 mg 3 times / week multiple, oral Recommended\|MTD Dose: 20 mg, 3 times / week Route: oral Route: multiple Dose: 20 mg, 3 times / week Co-administed with:: bortezomib(1.3 mg/m2) dexamethasone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf Page: p. 36, 45	unhealthy, 60 years (range: 28-79 years) n = 386 Health Status: unhealthy Age Group: 60 years (range: 28-79 years) Sex: M+F Population Size: 386 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf Page: p. 36, 45
Diarrhea	17 patients Disc. AE	20 mg 3 times / week multiple, oral Recommended\|MTD Dose: 20 mg, 3 times / week Route: oral Route: multiple Dose: 20 mg, 3 times / week Co-administed with:: bortezomib(1.3 mg/m2) dexamethasone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf Page: p. 36, 45	unhealthy, 60 years (range: 28-79 years) n = 386 Health Status: unhealthy Age Group: 60 years (range: 28-79 years) Sex: M+F Population Size: 386 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf Page: p. 36, 45
Thrombocytopenia	28% Disc. AE	20 mg 3 times / week multiple, oral Recommended\|MTD Dose: 20 mg, 3 times / week Route: oral Route: multiple Dose: 20 mg, 3 times / week Co-administed with:: bortezomib(1.3 mg/m2) dexamethasone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf Page: p. 36, 45	unhealthy, 60 years (range: 28-79 years) n = 386 Health Status: unhealthy Age Group: 60 years (range: 28-79 years) Sex: M+F Population Size: 386 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf Page: p. 36, 45
Thrombocytopenia	6 patients Disc. AE	20 mg 3 times / week multiple, oral Recommended\|MTD Dose: 20 mg, 3 times / week Route: oral Route: multiple Dose: 20 mg, 3 times / week Co-administed with:: bortezomib(1.3 mg/m2) dexamethasone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf Page: p. 36, 45	unhealthy, 60 years (range: 28-79 years) n = 386 Health Status: unhealthy Age Group: 60 years (range: 28-79 years) Sex: M+F Population Size: 386 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000CrossR.pdf Page: p. 36, 45
Hypoalbuminemia	grade 1-2, 2 patients	20 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21964801	unhealthy, 63.0 years (range: 43–75 years) n = 8 Health Status: unhealthy Condition: advanced solid tumors Age Group: 63.0 years (range: 43–75 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/21964801
Rash	grade 1-2, 3 patients	20 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21964801	unhealthy, 63.0 years (range: 43–75 years) n = 8 Health Status: unhealthy Condition: advanced solid tumors Age Group: 63.0 years (range: 43–75 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/21964801
Stomatitis	grade 1-2, 3 patients	20 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21964801	unhealthy, 63.0 years (range: 43–75 years) n = 8 Health Status: unhealthy Condition: advanced solid tumors Age Group: 63.0 years (range: 43–75 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/21964801
Vomiting	grade 1-2, 3 patients	20 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21964801	unhealthy, 63.0 years (range: 43–75 years) n = 8 Health Status: unhealthy Condition: advanced solid tumors Age Group: 63.0 years (range: 43–75 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/21964801
Fever	grade 1-2, 4 patients	20 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21964801	unhealthy, 63.0 years (range: 43–75 years) n = 8 Health Status: unhealthy Condition: advanced solid tumors Age Group: 63.0 years (range: 43–75 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/21964801
Nausea	grade 1-2, 4 patients	20 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21964801	unhealthy, 63.0 years (range: 43–75 years) n = 8 Health Status: unhealthy Condition: advanced solid tumors Age Group: 63.0 years (range: 43–75 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/21964801
Decreased appetite	grade 1-2, 5 patients	20 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21964801	unhealthy, 63.0 years (range: 43–75 years) n = 8 Health Status: unhealthy Condition: advanced solid tumors Age Group: 63.0 years (range: 43–75 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/21964801
Gamma glutamyl transpeptidase increased	grade 3, 1 patient DLT	20 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21964801	unhealthy, 63.0 years (range: 43–75 years) n = 8 Health Status: unhealthy Condition: advanced solid tumors Age Group: 63.0 years (range: 43–75 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/21964801
Fatigue	grade 3-4, 1 patient	20 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21964801	unhealthy, 63.0 years (range: 43–75 years) n = 8 Health Status: unhealthy Condition: advanced solid tumors Age Group: 63.0 years (range: 43–75 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/21964801
Leukopenia	grade 3-4, 2 patients	20 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21964801	unhealthy, 63.0 years (range: 43–75 years) n = 8 Health Status: unhealthy Condition: advanced solid tumors Age Group: 63.0 years (range: 43–75 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/21964801
Thrombocytopenia	grade 3-4, 2 patients	20 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21964801	unhealthy, 63.0 years (range: 43–75 years) n = 8 Health Status: unhealthy Condition: advanced solid tumors Age Group: 63.0 years (range: 43–75 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/21964801
Neutropenia	grade 3-4, 5 patients	20 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21964801	unhealthy, 63.0 years (range: 43–75 years) n = 8 Health Status: unhealthy Condition: advanced solid tumors Age Group: 63.0 years (range: 43–75 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/21964801
Arrhythmia	severe	20 mg 3 times / week multiple, oral Recommended\|MTD Dose: 20 mg, 3 times / week Route: oral Route: multiple Dose: 20 mg, 3 times / week Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf
Diarrhea	severe\|grade 5, 25%	20 mg 3 times / week multiple, oral Recommended\|MTD Dose: 20 mg, 3 times / week Route: oral Route: multiple Dose: 20 mg, 3 times / week Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf

Details

SMILES

InChI

DescriptionSources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdfCurator's Comment: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB06603

CNS Activity

Originator

Approval Year

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Conditions

Approved Use

Launch Date

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf
Curator's Comment: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB06603

C_max

T_1/2

F_unbound

Drug as perpetrator