KPT-276 | CAS#1421919-75-6 | Inhibitor of Exportin 1 (XPO1/CRM1)

MedKoo Cat#: 207153 | Name: KPT-276

Description:

WARNING: This product is for research use only, not for human or veterinary use.

KPT-276 is an orally bioavailable inhibitor of Exportin 1 (XPO1/CRM1) with anticancer activity.

Chemical Structure

KPT-276

CAS#1421919-75-6

Theoretical Analysis

MedKoo Cat#: 207153

Name: KPT-276

CAS#: 1421919-75-6

Chemical Formula: C16H10F8N4O

Exact Mass: 426.0727

Molecular Weight: 426.27

Elemental Analysis: C, 45.08; H, 2.36; F, 35.66; N, 13.14; O, 3.75

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,350.00	2 Weeks
500mg	USD 2,450.00	2 Weeks
1g	USD 3,650.00	2 Weeks
2g	USD 5,950.00	2 Weeks

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Related CAS #

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Synonym

KPT-276; KPT 276; KPT276;

IUPAC/Chemical Name

(2Z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1H-1,2,4-triazol-1-yl]-1-(3,3-difluoro-1-azetidinyl)-2-propen-1-one

InChi Key

JCHAWRDHMUSLMM-UPHRSURJSA-N

InChi Code

InChI=1S/C16H10F8N4O/c17-14(18)6-27(7-14)12(29)1-2-28-8-25-13(26-28)9-3-10(15(19,20)21)5-11(4-9)16(22,23)24/h1-5,8H,6-7H2/b2-1-

SMILES Code

O=C(N1CC(F)(F)C1)/C=C\N2N=C(C3=CC(C(F)(F)F)=CC(C(F)(F)F)=C3)N=C2

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

KPT-276 is an orally bioavailable selective CRM1 inhibitor.

In vitro activity:

The KPT-276 compound also significantly inhibited growth of both the human A375 (p<0.0001) and CHL-1 (p = 0.0087) melanoma cell lines as compared to control mice treated with diluent alone (Fig. 5A and 5B). Reference: PLoS One. 2014 Jul 24;9(7):e102983. https://pubmed.ncbi.nlm.nih.gov/25057921/

In vivo activity:

KPT-276 reduced monoclonal spikes in the Vk*MYC transgenic MM mouse model, and inhibited tumor growth in a xenograft MM mouse model. Reference: Leukemia. 2013 Dec;27(12):2357-65. https://pubmed.ncbi.nlm.nih.gov/23752175/

	Solvent	mg/mL	mM
Solubility
	DMSO	10.0	23.46
	DMF	10.0	23.45
	Water	0.0	0.00
	Ethanol	0.0	0.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 426.27 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Yang J, Bill MA, Young GS, La Perle K, Landesman Y, Shacham S, Kauffman M, Senapedis W, Kashyap T, Saint-Martin JR, Kendra K, Lesinski GB. Novel small molecule XPO1/CRM1 inhibitors induce nuclear accumulation of TP53, phosphorylated MAPK and apoptosis in human melanoma cells. PLoS One. 2014 Jul 24;9(7):e102983. doi: 10.1371/journal.pone.0102983. PMID: 25057921; PMCID: PMC4109950. 2. Zhang K, Wang M, Tamayo AT, Shacham S, Kauffman M, Lee J, Zhang L, Ou Z, Li C, Sun L, Ford RJ, Pham LV. Novel selective inhibitors of nuclear export CRM1 antagonists for therapy in mantle cell lymphoma. Exp Hematol. 2013 Jan;41(1):67-78.e4. doi: 10.1016/j.exphem.2012.09.002. Epub 2012 Sep 14. PMID: 22986101. 3. Schmidt J, Braggio E, Kortuem KM, Egan JB, Zhu YX, Xin CS, Tiedemann RE, Palmer SE, Garbitt VM, McCauley D, Kauffman M, Shacham S, Chesi M, Bergsagel PL, Stewart AK. Genome-wide studies in multiple myeloma identify XPO1/CRM1 as a critical target validated using the selective nuclear export inhibitor KPT-276. Leukemia. 2013 Dec;27(12):2357-65. doi: 10.1038/leu.2013.172. Epub 2013 Jun 11. PMID: 23752175; PMCID: PMC3922416. 4. Ranganathan P, Yu X, Na C, Santhanam R, Shacham S, Kauffman M, Walker A, Klisovic R, Blum W, Caligiuri M, Croce CM, Marcucci G, Garzon R. Preclinical activity of a novel CRM1 inhibitor in acute myeloid leukemia. Blood. 2012 Aug 30;120(9):1765-73. doi: 10.1182/blood-2012-04-423160. Epub 2012 Jun 7. PMID: 22677130; PMCID: PMC3433086.

In vitro protocol:

In vivo protocol:

1. Schmidt J, Braggio E, Kortuem KM, Egan JB, Zhu YX, Xin CS, Tiedemann RE, Palmer SE, Garbitt VM, McCauley D, Kauffman M, Shacham S, Chesi M, Bergsagel PL, Stewart AK. Genome-wide studies in multiple myeloma identify XPO1/CRM1 as a critical target validated using the selective nuclear export inhibitor KPT-276. Leukemia. 2013 Dec;27(12):2357-65. doi: 10.1038/leu.2013.172. Epub 2013 Jun 11. PMID: 23752175; PMCID: PMC3922416. 2. Ranganathan P, Yu X, Na C, Santhanam R, Shacham S, Kauffman M, Walker A, Klisovic R, Blum W, Caligiuri M, Croce CM, Marcucci G, Garzon R. Preclinical activity of a novel CRM1 inhibitor in acute myeloid leukemia. Blood. 2012 Aug 30;120(9):1765-73. doi: 10.1182/blood-2012-04-423160. Epub 2012 Jun 7. PMID: 22677130; PMCID: PMC3433086.

1: Giampetruzzi A, Danielson EW, Gumina V, Jeon M, Boopathy S, Brown RH, Ratti A, Landers JE, Fallini C. Modulation of actin polymerization affects nucleocytoplasmic transport in multiple forms of amyotrophic lateral sclerosis. Nat Commun. 2019 Aug 23;10(1):3827. doi: 10.1038/s41467-019-11837-y. PMID: 31444357; PMCID: PMC6707192. 2: Dolgin E. The brain's traffic problems. Science. 2019 Jan 18;363(6424):221-223. doi: 10.1126/science.363.6424.221. PMID: 30655425. 3: Muqbil I, Aboukameel A, Elloul S, Carlson R, Senapedis W, Baloglu E, Kauffman M, Shacham S, Bhutani D, Zonder J, Azmi AS, Mohammad RM. Anti-tumor activity of selective inhibitor of nuclear export (SINE) compounds, is enhanced in non- Hodgkin lymphoma through combination with mTOR inhibitor and dexamethasone. Cancer Lett. 2016 Dec 28;383(2):309-317. doi: 10.1016/j.canlet.2016.09.016. Epub 2016 Sep 28. PMID: 27693556; PMCID: PMC5584550. 4: Crochiere ML, Baloglu E, Klebanov B, Donovan S, Del Alamo D, Lee M, Kauffman M, Shacham S, Landesman Y. A method for quantification of exportin-1 (XPO1) occupancy by Selective Inhibitor of Nuclear Export (SINE) compounds. Oncotarget. 2016 Jan 12;7(2):1863-77. doi: 10.18632/oncotarget.6495. PMID: 26654943; PMCID: PMC4811503. 5: De Cesare M, Cominetti D, Doldi V, Lopergolo A, Deraco M, Gandellini P, Friedlander S, Landesman Y, Kauffman MG, Shacham S, Pennati M, Zaffaroni N. Anti-tumor activity of selective inhibitors of XPO1/CRM1-mediated nuclear export in diffuse malignant peritoneal mesothelioma: the role of survivin. Oncotarget. 2015 May 30;6(15):13119-32. doi: 10.18632/oncotarget.3761. PMID: 25948791; PMCID: PMC4537003. 6: Haines JD, Herbin O, de la Hera B, Vidaurre OG, Moy GA, Sun Q, Fung HY, Albrecht S, Alexandropoulos K, McCauley D, Chook YM, Kuhlmann T, Kidd GJ, Shacham S, Casaccia P. Nuclear export inhibitors avert progression in preclinical models of inflammatory demyelination. Nat Neurosci. 2015 Apr;18(4):511-20. doi: 10.1038/nn.3953. Epub 2015 Feb 23. PMID: 25706475; PMCID: PMC4522902. 7: Han X, Wang J, Shen Y, Zhang N, Wang S, Yao J, Shi Y. CRM1 as a new therapeutic target for non-Hodgkin lymphoma. Leuk Res. 2015 Jan;39(1):38-46. doi: 10.1016/j.leukres.2014.10.003. Epub 2014 Nov 4. PMID: 25466285. 8: Green AL, Ramkissoon SH, McCauley D, Jones K, Perry JA, Hsu JH, Ramkissoon LA, Maire CL, Hubbell-Engler B, Knoff DS, Shacham S, Ligon KL, Kung AL. Preclinical antitumor efficacy of selective exportin 1 inhibitors in glioblastoma. Neuro Oncol. 2015 May;17(5):697-707. doi: 10.1093/neuonc/nou303. Epub 2014 Nov 2. PMID: 25366336; PMCID: PMC4482855. 9: Yang J, Bill MA, Young GS, La Perle K, Landesman Y, Shacham S, Kauffman M, Senapedis W, Kashyap T, Saint-Martin JR, Kendra K, Lesinski GB. Novel small molecule XPO1/CRM1 inhibitors induce nuclear accumulation of TP53, phosphorylated MAPK and apoptosis in human melanoma cells. PLoS One. 2014 Jul 24;9(7):e102983. doi: 10.1371/journal.pone.0102983. PMID: 25057921; PMCID: PMC4109950. 10: Wang S, Han X, Wang J, Yao J, Shi Y. Antitumor effects of a novel chromosome region maintenance 1 (CRM1) inhibitor on non-small cell lung cancer cells in vitro and in mouse tumor xenografts. PLoS One. 2014 Mar 4;9(3):e89848. doi: 10.1371/journal.pone.0089848. PMID: 24595136; PMCID: PMC3942386. 11: Cheng Y, Holloway MP, Nguyen K, McCauley D, Landesman Y, Kauffman MG, Shacham S, Altura RA. XPO1 (CRM1) inhibition represses STAT3 activation to drive a survivin-dependent oncogenic switch in triple-negative breast cancer. Mol Cancer Ther. 2014 Mar;13(3):675-86. doi: 10.1158/1535-7163.MCT-13-0416. Epub 2014 Jan 15. PMID: 24431073; PMCID: PMC3954411. 12: Schmidt J, Braggio E, Kortuem KM, Egan JB, Zhu YX, Xin CS, Tiedemann RE, Palmer SE, Garbitt VM, McCauley D, Kauffman M, Shacham S, Chesi M, Bergsagel PL, Stewart AK. Genome-wide studies in multiple myeloma identify XPO1/CRM1 as a critical target validated using the selective nuclear export inhibitor KPT-276. Leukemia. 2013 Dec;27(12):2357-65. doi: 10.1038/leu.2013.172. Epub 2013 Jun 11. PMID: 23752175; PMCID: PMC3922416. 13: Salas Fragomeni RA, Chung HW, Landesman Y, Senapedis W, Saint-Martin JR, Tsao H, Flaherty KT, Shacham S, Kauffman M, Cusack JC. CRM1 and BRAF inhibition synergize and induce tumor regression in BRAF-mutant melanoma. Mol Cancer Ther. 2013 Jul;12(7):1171-9. doi: 10.1158/1535-7163.MCT-12-1171. Epub 2013 Apr 24. PMID: 23615632. 14: Zhang K, Wang M, Tamayo AT, Shacham S, Kauffman M, Lee J, Zhang L, Ou Z, Li C, Sun L, Ford RJ, Pham LV. Novel selective inhibitors of nuclear export CRM1 antagonists for therapy in mantle cell lymphoma. Exp Hematol. 2013 Jan;41(1):67-78.e4. doi: 10.1016/j.exphem.2012.09.002. Epub 2012 Sep 14. PMID: 22986101. 15: Ranganathan P, Yu X, Na C, Santhanam R, Shacham S, Kauffman M, Walker A, Klisovic R, Blum W, Caligiuri M, Croce CM, Marcucci G, Garzon R. Preclinical activity of a novel CRM1 inhibitor in acute myeloid leukemia. Blood. 2012 Aug 30;120(9):1765-73. doi: 10.1182/blood-2012-04-423160. Epub 2012 Jun 7. PMID: 22677130; PMCID: PMC3433086.