Selinexor - CAS 1393477-72-9
Catalog number: B0084-463408
Category: Inhibitor
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Selinexor is a potent and selective inhibitor of chromosome region maintenance 1 protein/exportin 1 (CRM1/XPO1). Selinexor was studied to show in vivo anti-leukaemic efficacy against T-ALL and acute myeloid leukaemia (AML) cells.
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Catalog Number Size Price Stock Quantity
B0084-463408 50 mg $298 In stock
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KPT-330; KPT 330; (Z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-N'-pyrazin-2-ylprop-2-enehydrazide
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1.Pharmacodynamic and genomic markers associated with response to the XPO1/CRM1 inhibitor selinexor (KPT-330): A report from the pediatric preclinical testing program.
Attiyeh EF, Maris JM1, Lock R2, Reynolds CP3, Kang MH3, Carol H2, Gorlick R4, Kolb EA5, Keir ST6, Wu J7, Landesman Y8, Shacham S8, Lyalin D9, Kurmasheva RT9, Houghton PJ9, Smith MA10. Pediatr Blood Cancer. 2016 Feb;63(2):276-86. doi: 10.1002/pbc.25727. Epub 2015 Sep 23.
BACKGROUND: Selinexor (KPT-330) is an inhibitor of the major nuclear export receptor, exportin 1 (XPO1, also termed chromosome region maintenance 1, CRM1) that has demonstrated activity in preclinical models and clinical activity against several solid and hematological cancers.
2.Targeting the Nuclear Export Protein XPO1/CRM1 Reverses Epithelial to Mesenchymal Transition.
Azmi AS1, Muqbil I1, Wu J1, Aboukameel A1, Senapedis W2, Baloglu E2, Bollig-Fischer A1, Dyson G1, Kauffman M2, Landesman Y2, Shacham S2, Philip PA1, Mohammad RM1,3. Sci Rep. 2015 Nov 5;5:16077. doi: 10.1038/srep16077.
Here we demonstrate for the first time that targeted inhibition of nuclear exporter protein exportin 1 (XPO1) also known as chromosome maintenance region 1 (CRM1) by Selective Inhibitor of Nuclear Export (SINE) compounds results in reversal of EMT in snail-transduced primary human mammary epithelial cells (HMECs). SINE compounds selinexor (KPT-330) and KPT-185, leptomycin B (LMB as +ve control) but not KPT-301 (-ve control) reverse EMT, suppress mesenchymal markers and consequently induce growth inhibition, apoptosis and prevent spheroid formation. SINE treatment resulted in nuclear retention of snail regulator FBXL5 that was concurrent with suppression of snail and down-regulation of mesenchymal markers. FBXL5 siRNA or transfection with cys528 mut-Xpo1 (lacking SINE binding site) markedly abrogated SINE activity highlighting an XPO1 and FBXL5 mediated mechanism of action. Silencing XPO1 or snail caused re-expression of FBXL5 as well as EMT reversal.
3.KPT-330, a potent and selective exportin-1 (XPO-1) inhibitor, shows antitumor effects modulating the expression of cyclin D1 and survivin [corrected] in prostate cancer models.
Gravina GL1, Mancini A2, Sanita P3, Vitale F4, Marampon F5, Ventura L6, Landesman Y7, McCauley D8, Kauffman M9, Shacham S10, Festuccia C11. BMC Cancer. 2015 Dec 1;15:941. doi: 10.1186/s12885-015-1936-z.
BACKGROUND AND AIMS: Increased expression of Chromosome Region Maintenance (CRM-1)/exportin-1 (XPO-1) has been correlated with poor prognosis in several aggressive tumors, making it an interesting therapeutic target. Selective Inhibitor of Nuclear Export (SINE) compounds bind to XPO-1 and block its ability to export cargo proteins. Here, we investigated the effects of a new class of SINE compounds in models of prostate cancer.
4.First-in-Class, First-in-Human Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Patients With Advanced Solid Tumors.
Abdul Razak AR1, Mau-Soerensen M2, Gabrail NY2, Gerecitano JF2, Shields AF2, Unger TJ2, Saint-Martin JR2, Carlson R2, Landesman Y2, McCauley D2, Rashal T2, Lassen U2, Kim R2, Stayner LA2, Mirza MR2, Kauffman M2, Shacham S2, Mahipal A2. J Clin Oncol. 2016 Feb 29. pii: JCO653949. [Epub ahead of print]
PURPOSE: This trial evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of selinexor (KPT-330), a novel, oral small-molecule inhibitor of exportin 1 (XPO1/CRM1), and determined the recommended phase II dose.
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CAS 1393477-72-9 Selinexor

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