selinexor   Click here for help

GtoPdb Ligand ID: 10036

Synonyms: compound 70 [WO2013019561A1] | KPT-330 | KPT330 | Nexpovio® | Xpovio®
Approved drug Immunopharmacology Ligand
selinexor is an approved drug (FDA (2019), EMA (2021))
Compound class: Synthetic organic
Comment: Selinexor (KPT-330) is an inhibitor of the nuclear export protein XPO1 (a.k.a. exportin 1) that is being developed as an anti-neoplastic agent by Karyopharm Therapeutics. It is a first-in-class inhibitor that exploits a novel mechanism of action compared to existing chemotherapeutics [2,7-8]. The chemical structure is claimed in patent WO2013019561A1 (as compound 70) [9].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Click here for structure editor
Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 7
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 97.62
Molecular weight 443.09
XLogP 3.63
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES O=C(C=Cn1cnc(n1)c1cc(cc(c1)C(F)(F)F)C(F)(F)F)NNc1cnccn1
Isomeric SMILES O=C(/C=C\n1cnc(n1)c1cc(cc(c1)C(F)(F)F)C(F)(F)F)NNc1cnccn1
InChI 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-
InChI Key DEVSOMFAQLZNKR-RJRFIUFISA-N
References
1. Garg M, Kanojia D, Mayakonda A, Ganesan TS, Sadhanandhan B, Suresh S, S S, Nagare RP, Said JW, Doan NB et al.. (2017)
Selinexor (KPT-330) has antitumor activity against anaplastic thyroid carcinoma in vitro and in vivo and enhances sensitivity to doxorubicin.
Sci Rep, 7 (1): 9749. [PMID:28852098]
2. Gerecitano J. (2014)
SINE (selective inhibitor of nuclear export)--translational science in a new class of anti-cancer agents.
J Hematol Oncol, 7: 67. [PMID:25281264]
3. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL et al.. (2020)
A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.
Nature, 583 (7816): 459-468. [PMID:32353859]
4. Gravina GL, Mancini A, Colapietro A, Marampon F, Sferra R, Pompili S, Biordi LA, Iorio R, Flati V, Argueta C et al.. (2017)
Pharmacological treatment with inhibitors of nuclear export enhances the antitumor activity of docetaxel in human prostate cancer.
Oncotarget, 8 (67): 111225-111245. [PMID:29340049]
5. Kudo N, Khochbin S, Nishi K, Kitano K, Yanagida M, Yoshida M, Horinouchi S. (1997)
Molecular cloning and cell cycle-dependent expression of mammalian CRM1, a protein involved in nuclear export of proteins.
J Biol Chem, 272 (47): 29742-51. [PMID:9368044]
6. Nie D, Huang K, Yin S, Li Y, Xie S, Ma L, Wang X, Wu Y, Xiao J, Wang J et al.. (2018)
KPT-330 inhibition of chromosome region maintenance 1 is cytotoxic and sensitizes chronic myeloid leukemia to Imatinib.
Cell Death Discov, 4: 48. [PMID:29707241]
7. Pal I, Safari M, Jovanovic M, Bates SE, Deng C. (2019)
Targeting Translation of mRNA as a Therapeutic Strategy in Cancer.
Curr Hematol Malig Rep, 14 (4): 219-227. [PMID:31231778]
8. Parikh K, Cang S, Sekhri A, Liu D. (2014)
Selective inhibitors of nuclear export (SINE)--a novel class of anti-cancer agents.
J Hematol Oncol, 7: 78. [PMID:25316614]
9. Sandanayaka VP, Shacham S, Kauffman M, Schechter S, Mccauley D, Landesman Y, Senapedis W, Saint-Martin J-R. (2013)
Nuclear transport modulators and uses thereof.
Patent number: WO2013019561A1. Assignee: Karyopharm Therapeutics, Inc.. Priority date: 29/07/2011. Publication date: 04/07/2013.
10. Widman DG, Gornisiewicz S, Shacham S, Tamir S. (2018)
In vitro toxicity and efficacy of verdinexor, an exportin 1 inhibitor, on opportunistic viruses affecting immunocompromised individuals.
PLoS ONE, 13 (10): e0200043. [PMID:30332435]
11. Wu M, Gui H, Feng Z, Xu H, Li G, Li M, Chen T, Wu Y, Huang J, Bai Z et al.. (2018)
KPT-330, a potent and selective CRM1 inhibitor, exhibits anti-inflammation effects and protection against sepsis.
Biochem Biophys Res Commun, 503 (3): 1773-1779. [PMID:30064906]