SELINEXOR

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H11F6N7O
Molecular Weight	443.306
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC(F)(F)C1=CC(=CC(=C1)C2=NN(C=N2)\C=C/C(=O)NNC3=NC=CN=C3)C(F)(F)F

InChI

InChIKey=DEVSOMFAQLZNKR-RJRFIUFISA-N

InChI=1S/C17H11F6N7O/c18-16(19,20)11-5-10(6-12(7-11)17(21,22)23)15-26-9-30(29-15)4-1-14(31)28-27-13-8-24-2-3-25-13/h1-9H,(H,25,27)(H,28,31)/b4-1-

HIDE SMILES / InChI

Molecular Formula	C17H11F6N7O
Molecular Weight	443.306
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26956669 | https://www.karyopharm.com/pipeline/oral-selinexor-kpt-330/ | https://www.ncbi.nlm.nih.gov/pubmed/27893412http://karyopharm.com/pipeline/oral-selinexor-kpt-330/

Selinexor (KPT-330) is a first in class XPO1 antagonist being evaluated in multiple later stage clinical trials in patients with relapsed and/or refractory hematological and solid tumor malignancies.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Exportin-1 8 Target ID: CHEMBL5661 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26956669	Inhibitor 8297
Exportin-1 8 Target ID: CHEMBL5661 Sources: http://www.ncbi.nlm.nih.gov/pubmed/22847027	Blocker 537

Conditions

Condition	Modality	Highest Phase	Product
Liposarcoma 6 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27893412	Primary	Phase III 656	Unknown Approved Use Unknown
Multiple myeloma 159 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28604120	Primary	Phase III 656	Unknown Approved Use Unknown
Acute myeloid leukemia 136 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28336527	Primary	Phase I 428	Unknown Approved Use Unknown
Dedifferentiated liposarcoma 2 Sources: https://clinicaltrials.gov/show/NCT02606461	Primary	Phase III 656	Unknown Approved Use Unknown
Acute myeloid leukemia (relapsed/refractory) 2 Sources: https://clinicaltrials.gov/show/NCT02249091	Primary	Phase II 1132	Unknown Approved Use Unknown
Breast cancer 434 Sources: https://clinicaltrials.gov/show/NCT02025985	Primary	Phase II 1132	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: https://clinicaltrials.gov/show/NCT02025985	Primary	Phase II 1132	Unknown Approved Use Unknown
Endometrial cancer 43 Sources: https://clinicaltrials.gov/show/NCT02025985	Primary	Phase II 1132	Unknown Approved Use Unknown
Cervical cancer 40 Sources: https://clinicaltrials.gov/show/NCT02025985	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
680 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212306s000lbl.pdf	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:		SELINEXOR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
5386 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212306s000lbl.pdf	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:		SELINEXOR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
7 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212306s000lbl.pdf	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:		SELINEXOR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212306s000lbl.pdf	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:		SELINEXOR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	Other AEs: Thrombocytopenia, Thrombocytopenia... Other AEs: Thrombocytopenia (grade 4, 1%) Thrombocytopenia (grade 3, 23%) Thrombocytopenia (grade 1-2, 22%) Hyponatremia (grade 4, 1%) Hyponatremia (grade 3, 8%) Hyponatremia (grade 1-2, 3%) Nausea (grade 3, 12%) Nausea (grade 1-2, 60%) Fatigue (grade 3, 14%) Fatigue (grade 1-2, 52%) Decreased appetite (grade 3, 5%) Decreased appetite (grade 1-2, 49%) Vomiting (grade 3, 7%) Vomiting (grade 1-2, 49%) Weight loss (grade 1-2, 55%) Anemia (grade 3, 11%) Anemia (grade 1-2, 29%) Dysgeusia (grade 1-2, 30%) Blurred vision (grade 3, 1%) Blurred vision (grade 1-2, 21%) Diarrhea (grade 3, 1%) Diarrhea (grade 1-2, 19%) Constipation (grade 1-2, 8%) Dizziness (grade 1-2, 14%) Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
60 mg 2 times / week multiple, oral Dose: 60 mg, 2 times / week Route: oral Route: multiple Dose: 60 mg, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/32589977	unhealthy, 67 years (range: 35–87 years) n = 127 Health Status: unhealthy Age Group: 67 years (range: 35–87 years) Sex: M+F Population Size: 127 Sources: https://pubmed.ncbi.nlm.nih.gov/32589977	Disc. AE: Diarrhea, Pyrexia... Other AEs: Thrombocytopenia, Neutropenia... AEs leading to discontinuation/dose reduction: Diarrhea (grade 3, 3%) Pyrexia (grade 3, 4%) Other AEs: Thrombocytopenia (grade 4, 15%) Neutropenia (grade 4, 9%) Anaemia (grade 4, 1%) Fatigue (grade 3, 11%) Hyponatraemia (grade 3, 8%) Nausea (grade 3, 6%) Dyspnoea (grade 4, 1%) Acute respiratory distress syndrome (grade 5, 1 patient) Cerebrovascular accident (grade 5, 1 patient) Sepsis (grade 5, 3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/32589977
100 mg 2 times / week multiple, oral Highest studied dose Dose: 100 mg, 2 times / week Route: oral Route: multiple Dose: 100 mg, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/32589977	unhealthy n = 92 Health Status: unhealthy Population Size: 92 Sources: https://pubmed.ncbi.nlm.nih.gov/32589977	Sources: https://pubmed.ncbi.nlm.nih.gov/32589977

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inducer 781	inhibitor 1767		inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP3A4/5 278 OATP1B3 706	CYP3A 191 P-gp 1537 BCRP 561 OATP1B1 406 OATP1B3 350 OAT1 326 OAT3 339 OCT1 327 OCT2 355 MATE1 135 MATE2 96	CYP1A2 701 CYP2B6 547

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=49 Page: 49.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=49 Page: 49.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=49 Page: 49.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=49 Page: 49.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=49 Page: 49.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=49 Page: 49.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=49 Page: 49.0	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=49 Page: 49.0	no
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=49 Page: 49.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=49 Page: 49.0	yes [IC50 6.2 uM]

Drug as victim

Target	Modality	Activity
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=48 Page: 48.0	no
MATE1 135	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=48 Page: 48.0	no
MATE2 96	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=48 Page: 48.0	no
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=48 Page: 48.0	no
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=48 Page: 48.0	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=48 Page: 48.0	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=48 Page: 48.0	no
OCT1 327	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=48 Page: 48.0	no
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=48 Page: 48.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=48 Page: 48.0	no
CYP3A 191	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=55 Page: 55.0	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=49 Page: 49.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf#page=33 Page: 33.0

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA001APV	https://www.aablocks.com/goods/Goods/detail?id=AA001APV
AK Scientific, Inc. (AKSCI)	2500AH	http://www.aksci.com/item_detail.php?cat=2500AH
Aaron Chemicals	AR001BHN	http://www.aaronchem.com/1393477-72-9
Achemtek	0102-028691	http://www.achemtek.com/1393477-72-9
Adooq BioScience	A12582	https://www.adooq.com/kpt-330.html
ApexBio Technology	B1464	http://www.apexbt.com/kpt-330.html
AvaChem Scientific	6779	https://www.avachem.com/productSearch.asp?6779
BLD Pharm	BD00799126	http://www.bldpharm.com/products/1621865-82-4.html
BioCrick	BCC4446	http://www.biocrick.com/KPT-330-BCC4446.html
BioSynth	J-690156	https://www.biosynth.com/en/products/all-products/products/J-690177.html
ChemShuttle	141891	http://www.chemshuttle.com/catalogsearch/result/?q=1393477-72-9&cat=
Chemspace	CSSB00025704619	https://chem-space.com/CSSB00025704619
DC Chemicals	DC7067	http://www.dcchemicals.com/product_show-KPT_330_Selinexor_.html
Excenen	EX-A870	http://www.excenen.com/searchresultlist.php?id=1393477-72-9
Lab Network	LN01288396	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01288396
Smolecule	S542946	http://www.smolecule.com/products/s542946
Smolecule	S542947	http://www.smolecule.com/products/s542947
THE BioTek	bt-282530	https://www.thebiotek.com/product/inhibitors/bt-282530
THE BioTek	bt-282531	https://www.thebiotek.com/product/inhibitors/bt-282531
TubePharm	Tube706	http://www.tubepharm.com/product/1393477-72-9-en.html
Yuhao Chemical	YH65264	http://www.chemyuhao.com/1393477-72-9.html
abcr GmbH	AB479559	http://www.abcr.com/shop/en/AB479559
eNovation Chemicals	D571663	https://www.enovationchem.com/ProductDetails.asp?ProductID=D571663

PubMed

Title	Date	PubMed
Antileukemic activity of nuclear export inhibitors that spare normal hematopoietic cells.	2013 Jan	22847027
Mitochondrial pyruvate carrier regulates autophagy, inflammation, and neurodegeneration in experimental models of Parkinson's disease.	2016 Dec 7	27928028
CRM1 Inhibition Promotes Cytotoxicity in Ewing Sarcoma Cells by Repressing EWS-FLI1-Dependent IGF-1 Signaling.	2016 May 1	26956669
Selinexor (KPT-330) has antitumor activity against anaplastic thyroid carcinoma in vitro and in vivo and enhances sensitivity to doxorubicin.	2017 Aug 29	28852098
Molecular mechanism and therapeutic implications of selinexor (KPT-330) in liposarcoma.	2017 Jan 31	27893412
Inhibition of exportin-1 function results in rapid cell cycle-associated DNA damage in cancer cells.	2017 Jun 13	28467801

Patents

Sample Use Guides

In Vivo Use Guide

60 mg (∼35 mg/m2) given twice weekly in a 4-week cycle based on the totality of safety and efficacy data.

Route of Administration: Oral

In Vitro Use Guide

To determine whether inhibition of cell growth was due to an alteration in the cell cycle, we analyzed cell cycle distribution of Anaplastic thyroid carcinoma (ATC) cells either exposed to various concentrations (0–1000 nM, 48 h) of selinexor or XPO1 was silenced by transfection with XPO1 shRNA. XPO1 inhibition significantly increased G1 phase and decreased the S and G2/M phases in ATC cells. Of note, selinexor treatment resulted in cell cycle arrest in a dose-dependent manner. Further, was observed that selinexor altered the expression of its known cargo proteins (e.g., p53, p27 and p21), as well as indirect targets including cyclin B1, cyclin D1 in the ATC cell lines. Selinexor treatment (1000 nM, 24 h) also increased cleaved PARP, cleaved caspase-9 and cleaved caspase-3 in ATC cells. Cleavage of PARP [poly (ADP-ribose) polymerase is one of the hallmarks of apoptosis and caspase activation. This was associated with a decrease in the protein levels of anti-apoptotic proteins such as MCL1 and C-Myc. Moreover, was evaluated the dose-dependent effect of selinexor on the protein expression of a few important genes in CAL62 cells

Substance Class	Chemical Created by `admin` on `Sat Dec 16 10:45:00 GMT 2023` Edited by `admin` on `Sat Dec 16 10:45:00 GMT 2023`
Record UNII	31TZ62FO8F
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

SELINEXOR

Official Name

English

SELINEXOR [USAN]

Common Name

English

(Z)-3-(3-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)-1H-1,2,4-TRIAZOL-1-YL)-N'-(PYRAZIN-2-YL)ACRYLOHYDRAZIDE

Systematic Name

English

selinexor [INN]

Common Name

English

KPT-330

Code

English

2-PROPENOIC ACID, 3-(3-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)-1H-1,2,4-TRIAZOL-1-YL)-, 2-(2-PYRAZINYL)HYDRAZIDE, (2Z)-

Systematic Name

English

SELINEXOR [MI]

Common Name

English

Selinexor [WHO-DD]

Common Name

English

XPOVIO

Brand Name

English

SELINEXOR [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

880222

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

FDA ORPHAN DRUG

825721

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

NCI_THESAURUS

C274

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

FDA ORPHAN DRUG

459014

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

FDA ORPHAN DRUG

527816

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

FDA ORPHAN DRUG

436414

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

EU-Orphan Drug

EU/3/14/1355

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

FDA ORPHAN DRUG

432414

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

Code System Code Type Description

FDA UNII

31TZ62FO8F

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

PRIMARY

EVMPD

SUB177942

Created by admin on Sat Dec 16 10:45:00 GMT 2023 , Edited by admin on Sat Dec 16 10:45:00 GMT 2023

PRIMARY

CAS

1393477-72-9

Created by admin on Sat Dec 16 10:45:00 GMT 2023 , Edited by admin on Sat Dec 16 10:45:00 GMT 2023

PRIMARY

SMS_ID

100000163576

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

PRIMARY

DRUG BANK

DB11942

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

PRIMARY

DAILYMED

31TZ62FO8F

Created by admin on Sat Dec 16 10:45:00 GMT 2023 , Edited by admin on Sat Dec 16 10:45:00 GMT 2023

PRIMARY

PUBCHEM

71481097

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

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EPA CompTox

DTXSID801026013

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

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NCI_THESAURUS

C102546

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

PRIMARY

LACTMED

Selinexor

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

PRIMARY

DRUG CENTRAL

5330

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

PRIMARY

MERCK INDEX

m12226

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

PRIMARY

RXCUI

2178390

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

PRIMARY

USAN

CD-85

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

PRIMARY

WIKIPEDIA

Selinexor

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

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INN

9872

Created by admin on Sat Dec 16 10:45:01 GMT 2023 , Edited by admin on Sat Dec 16 10:45:01 GMT 2023

PRIMARY

ChEMBL

CHEMBL3545185

Created by admin on Sat Dec 16 10:45:00 GMT 2023 , Edited by admin on Sat Dec 16 10:45:00 GMT 2023

PRIMARY

Related Record Type Details


					CAX2OJK5R8

EXPORTIN-1

TARGET -> INHIBITOR

Comments:

In cell-based assays, selinexor inhibits XPO1-mediated nuclear export with an IC50≈20 nM.

Qualification:

IC50

Amount:


					PUO0521HZV

CYTOCHROME P450 3A4

METABOLIC ENZYME -> SUBSTRATE

Interaction Type:

MAJOR


					66DDF797LP

OATP-8

TRANSPORTER -> INHIBITOR

Comments:

In vitro, selinexor inhibits OATP1B3 with an IC50 value of 6.20 μM.

Qualification:

IC50

Amount:


					6D53G0FD0Z

PLASMA PROTEIN FRACTION (HUMAN)

BINDER->LIGAND

Interaction Type:

BINDING

Amount:

Related Record Type Details


					MVY2AE6R24

KPT-330, (E)-

METABOLITE LESS ACTIVE -> PARENT

Comments:

HAS ABOUT 10% OF ACTIVITY OF Selinexor

Interaction Type:

MAJOR

Qualification:

PLASMA

Related Record Type Details


					31TZ62FO8F

SELINEXOR

ACTIVE MOIETY

Name	Property Type	Parameters
Volume of Distribution	PHARMACOKINETIC

Tmax	PHARMACOKINETIC	ORAL ADMINISTRATION

Biological Half-life	PHARMACOKINETIC

Blood-to-plasma ratio	PHARMACOKINETIC

AE	Significance	Dose	Population
Dizziness	grade 1-2, 14%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Diarrhea	grade 1-2, 19%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Blurred vision	grade 1-2, 21%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Thrombocytopenia	grade 1-2, 22%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Anemia	grade 1-2, 29%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Hyponatremia	grade 1-2, 3%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Dysgeusia	grade 1-2, 30%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Decreased appetite	grade 1-2, 49%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Vomiting	grade 1-2, 49%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Fatigue	grade 1-2, 52%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Weight loss	grade 1-2, 55%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Nausea	grade 1-2, 60%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Constipation	grade 1-2, 8%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Blurred vision	grade 3, 1%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Diarrhea	grade 3, 1%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Anemia	grade 3, 11%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Nausea	grade 3, 12%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Fatigue	grade 3, 14%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Thrombocytopenia	grade 3, 23%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Decreased appetite	grade 3, 5%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Vomiting	grade 3, 7%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Hyponatremia	grade 3, 8%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Hyponatremia	grade 4, 1%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Thrombocytopenia	grade 4, 1%	50 mg/m2 2 times / week multiple, oral Dose: 50 mg/m2, 2 times / week Route: oral Route: multiple Dose: 50 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/31822399	unhealthy, 63 years (range: 31-80 years) n = 73 Health Status: unhealthy Age Group: 63 years (range: 31-80 years) Sex: M+F Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/31822399
Fatigue	grade 3, 11%	60 mg 2 times / week multiple, oral Dose: 60 mg, 2 times / week Route: oral Route: multiple Dose: 60 mg, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/32589977	unhealthy, 67 years (range: 35–87 years) n = 127 Health Status: unhealthy Age Group: 67 years (range: 35–87 years) Sex: M+F Population Size: 127 Sources: https://pubmed.ncbi.nlm.nih.gov/32589977
Diarrhea	grade 3, 3% Disc. AE	60 mg 2 times / week multiple, oral Dose: 60 mg, 2 times / week Route: oral Route: multiple Dose: 60 mg, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/32589977	unhealthy, 67 years (range: 35–87 years) n = 127 Health Status: unhealthy Age Group: 67 years (range: 35–87 years) Sex: M+F Population Size: 127 Sources: https://pubmed.ncbi.nlm.nih.gov/32589977
Pyrexia	grade 3, 4% Disc. AE	60 mg 2 times / week multiple, oral Dose: 60 mg, 2 times / week Route: oral Route: multiple Dose: 60 mg, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/32589977	unhealthy, 67 years (range: 35–87 years) n = 127 Health Status: unhealthy Age Group: 67 years (range: 35–87 years) Sex: M+F Population Size: 127 Sources: https://pubmed.ncbi.nlm.nih.gov/32589977
Nausea	grade 3, 6%	60 mg 2 times / week multiple, oral Dose: 60 mg, 2 times / week Route: oral Route: multiple Dose: 60 mg, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/32589977	unhealthy, 67 years (range: 35–87 years) n = 127 Health Status: unhealthy Age Group: 67 years (range: 35–87 years) Sex: M+F Population Size: 127 Sources: https://pubmed.ncbi.nlm.nih.gov/32589977
Hyponatraemia	grade 3, 8%	60 mg 2 times / week multiple, oral Dose: 60 mg, 2 times / week Route: oral Route: multiple Dose: 60 mg, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/32589977	unhealthy, 67 years (range: 35–87 years) n = 127 Health Status: unhealthy Age Group: 67 years (range: 35–87 years) Sex: M+F Population Size: 127 Sources: https://pubmed.ncbi.nlm.nih.gov/32589977
Anaemia	grade 4, 1%	60 mg 2 times / week multiple, oral Dose: 60 mg, 2 times / week Route: oral Route: multiple Dose: 60 mg, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/32589977	unhealthy, 67 years (range: 35–87 years) n = 127 Health Status: unhealthy Age Group: 67 years (range: 35–87 years) Sex: M+F Population Size: 127 Sources: https://pubmed.ncbi.nlm.nih.gov/32589977
Dyspnoea	grade 4, 1%	60 mg 2 times / week multiple, oral Dose: 60 mg, 2 times / week Route: oral Route: multiple Dose: 60 mg, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/32589977	unhealthy, 67 years (range: 35–87 years) n = 127 Health Status: unhealthy Age Group: 67 years (range: 35–87 years) Sex: M+F Population Size: 127 Sources: https://pubmed.ncbi.nlm.nih.gov/32589977
Thrombocytopenia	grade 4, 15%	60 mg 2 times / week multiple, oral Dose: 60 mg, 2 times / week Route: oral Route: multiple Dose: 60 mg, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/32589977	unhealthy, 67 years (range: 35–87 years) n = 127 Health Status: unhealthy Age Group: 67 years (range: 35–87 years) Sex: M+F Population Size: 127 Sources: https://pubmed.ncbi.nlm.nih.gov/32589977
Neutropenia	grade 4, 9%	60 mg 2 times / week multiple, oral Dose: 60 mg, 2 times / week Route: oral Route: multiple Dose: 60 mg, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/32589977	unhealthy, 67 years (range: 35–87 years) n = 127 Health Status: unhealthy Age Group: 67 years (range: 35–87 years) Sex: M+F Population Size: 127 Sources: https://pubmed.ncbi.nlm.nih.gov/32589977
Acute respiratory distress syndrome	grade 5, 1 patient	60 mg 2 times / week multiple, oral Dose: 60 mg, 2 times / week Route: oral Route: multiple Dose: 60 mg, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/32589977	unhealthy, 67 years (range: 35–87 years) n = 127 Health Status: unhealthy Age Group: 67 years (range: 35–87 years) Sex: M+F Population Size: 127 Sources: https://pubmed.ncbi.nlm.nih.gov/32589977
Cerebrovascular accident	grade 5, 1 patient	60 mg 2 times / week multiple, oral Dose: 60 mg, 2 times / week Route: oral Route: multiple Dose: 60 mg, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/32589977	unhealthy, 67 years (range: 35–87 years) n = 127 Health Status: unhealthy Age Group: 67 years (range: 35–87 years) Sex: M+F Population Size: 127 Sources: https://pubmed.ncbi.nlm.nih.gov/32589977
Sepsis	grade 5, 3 patients	60 mg 2 times / week multiple, oral Dose: 60 mg, 2 times / week Route: oral Route: multiple Dose: 60 mg, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/32589977	unhealthy, 67 years (range: 35–87 years) n = 127 Health Status: unhealthy Age Group: 67 years (range: 35–87 years) Sex: M+F Population Size: 127 Sources: https://pubmed.ncbi.nlm.nih.gov/32589977

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/26956669 | https://www.karyopharm.com/pipeline/oral-selinexor-kpt-330/ | https://www.ncbi.nlm.nih.gov/pubmed/27893412http://karyopharm.com/pipeline/oral-selinexor-kpt-330/

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Approved Use

Approved Use

Approved Use

Approved Use

Approved Use

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Approved Use

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: https://www.ncbi.nlm.nih.gov/pubmed/26956669 | https://www.karyopharm.com/pipeline/oral-selinexor-kpt-330/ | https://www.ncbi.nlm.nih.gov/pubmed/27893412http://karyopharm.com/pipeline/oral-selinexor-kpt-330/

C_max

T_1/2

F_unbound

Drug as perpetrator