eltanexor   Click here for help

GtoPdb Ligand ID: 10037

Synonyms: KPT-8602 | KPT8602
Compound class: Synthetic organic
Comment: Eltanexor (KPT-8602) is a second-generation, orally bioavailable, selective inhibitor of the nuclear export protein XPO1, that works in the same way as its first-in-class relation selinexor. In comparison to selinexor, eltanexor exhibits much lower brain penetration, and this appears to reduce the central nervous system-mediated side effects of anorexia and weight loss detected with selinexor therapy [1]. Eltanexor is being investigated for therapeutic antineoplastic potential [1-3].

eltanexor is commercially available from our sponsors

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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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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 6
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 99.58
Molecular weight 428.08
XLogP 2.52
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES NC(=O)C(=Cn1cnc(n1)c1cc(cc(c1)C(F)(F)F)C(F)(F)F)c1cncnc1
Isomeric SMILES NC(=O)/C(=C/n1cnc(n1)c1cc(cc(c1)C(F)(F)F)C(F)(F)F)/c1cncnc1
InChI InChI=1S/C17H10F6N6O/c18-16(19,20)11-1-9(2-12(3-11)17(21,22)23)15-27-8-29(28-15)6-13(14(24)30)10-4-25-7-26-5-10/h1-8H,(H2,24,30)/b13-6+
InChI Key JFBAVWVBLRIWHM-AWNIVKPZSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
KPT-8602 is being evaluated as a single agent in Phase 1/2 clinical trial NCT02649790, in patients with relapsed/refractory cancers (both haematological and solid tumours).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
XPO1 is the major facilitator of nuclear export of key tumour suppressor proteins (TSPs) including p53, p73, BRCA1/2, pRB and FOXO. Cancer cells may overexpress XPO1 and this leads to mislocalisation of TSPs to the cytoplasm and allows cancer cells to defeat TSP-regulated apoptosis, and to proliferate in an uncontrolled manner. Pharmacological inhibition of XPO1 prevents XPO1-mediated nuclear export of TSPs, and restores their accumulation in the nucleus, and thie pro-apoptotic function in damaged cancer cells. As XPO1 is minimally expressed in normal cells these are spared the cytotoxic effects of eltanexor that manifest in cancer cells. Haematologic tumours are particularly susceptible to apoptosis induction by XPO1 inhibition, and these cancers are a major target of clinical trials of XPO1 inhibiting compounds [1,3].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02649790 Study of the Safety, Tolerability and Efficacy of KPT-8602 in Patients With Relapsed/Refractory Cancer Indications Phase 1/Phase 2 Interventional Karyopharm Therapeutics Inc