exportin 1 | Nuclear export proteins | IUPHAR/MMV Guide to MALARIA PHARMACOLOGY

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exportin 1

Target id: 3014

Nomenclature: exportin 1

Family: Nuclear export proteins

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1071 2p15 XPO1 exportin 1
Mouse - 1071 11 A3.2 Xpo1 exportin 1
Rat - 1071 14q22 Xpo1 exportin 1
Previous and Unofficial Names
chromosome region maintenance 1 | CRM1 | exportin-1 | exp1
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
selinexor Hs Inhibition - - 6
[6]
eltanexor Hs Inhibition - - 2,4,8
[2,4,8]
General Comments
Exportin 1 (XPO1) is a major nuclear-cytoplasmic exporter, that in eukaryotes regulates transfer of ~220 endogenous cargo proteins that contain a leucine-rich nuclear export signal (NES). It also binds to and exports HIV-1 Rev and HTLV-1 Rex proteins. Exportin 1 affinity for cargo proteins is regulated by binding of Ran-GTP in the nucleus, and Ran-GAP-mediated Ran-GTP hydrolysis releases the cargo proteins in the cytoplasm. Exportin 1 cargo proteins include tumour suppressor proteins (TSPs), apoptosis inducers and cell cycle regulators. A number of haematologic malignancies and solid tumours have been discovered to be dependent on Exportin 1-mediated nuclear export (particularly export of TSPs) for their survival. In light of this evidence, exportin 1 is being exploited as an oncology drug target [1,3,5,7]. Selinexor (KPT-330) and eltanexor (KPT-8602) are orally bioavailable and selective exportin 1 inhibitors that are in clinical development as novel chemotherapeutics for haematological and solid cancers.

References

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1. De Cesare M, Cominetti D, Doldi V, Lopergolo A, Deraco M, Gandellini P, Friedlander S, Landesman Y, Kauffman MG, Shacham S et al.. (2015) Anti-tumor activity of selective inhibitors of XPO1/CRM1-mediated nuclear export in diffuse malignant peritoneal mesothelioma: the role of survivin. Oncotarget, 6 (15): 13119-32. [PMID:25948791]

2. Etchin J, Berezovskaya A, Conway AS, Galinsky IA, Stone RM, Baloglu E, Senapedis W, Landesman Y, Kauffman M, Shacham S et al.. (2017) KPT-8602, a second-generation inhibitor of XPO1-mediated nuclear export, is well tolerated and highly active against AML blasts and leukemia-initiating cells. Leukemia, 31 (1): 143-150. [PMID:27211268]

3. Gravina GL, Senapedis W, McCauley D, Baloglu E, Shacham S, Festuccia C. (2014) Nucleo-cytoplasmic transport as a therapeutic target of cancer. J Hematol Oncol, 7: 85. [PMID:25476752]

4. Hing ZA, Fung HY, Ranganathan P, Mitchell S, El-Gamal D, Woyach JA, Williams K, Goettl VM, Smith J, Yu X et al.. (2016) Next-generation XPO1 inhibitor shows improved efficacy and in vivo tolerability in hematological malignancies. Leukemia, 30 (12): 2364-2372. [PMID:27323910]

5. Mendonca J, Sharma A, Kim HS, Hammers H, Meeker A, De Marzo A, Carducci M, Kauffman M, Shacham S, Kachhap S. (2014) Selective inhibitors of nuclear export (SINE) as novel therapeutics for prostate cancer. Oncotarget, 5 (15): 6102-12. [PMID:25026284]

6. 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.

7. Senapedis WT, Baloglu E, Landesman Y. (2014) Clinical translation of nuclear export inhibitors in cancer. Semin. Cancer Biol., 27: 74-86. [PMID:24755012]

8. Vercruysse T, De Bie J, Neggers JE, Jacquemyn M, Vanstreels E, Schmid-Burgk JL, Hornung V, Baloglu E, Landesman Y, Senapedis W et al.. (2017) The Second-Generation Exportin-1 Inhibitor KPT-8602 Demonstrates Potent Activity against Acute Lymphoblastic Leukemia. Clin. Cancer Res., 23 (10): 2528-2541. [PMID:27780859]

How to cite this page

Nuclear export proteins: exportin 1. Last modified on 03/08/2018. Accessed on 14/07/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3014.