IUPAC/Chemical Name
propan-2-yl (Z)-3-[3-[3-methoxy-5-(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]prop-2-enoate
InChi Key
NLNGWFLRRRYNIL-PLNGDYQASA-N
InChi Code
InChI=1S/C16H16F3N3O3/c1-10(2)25-14(23)4-5-22-9-20-15(21-22)11-6-12(16(17,18)19)8-13(7-11)24-3/h4-10H,1-3H3/b5-4-
SMILES Code
COC1=CC(C2=NN(/C=C\C(OC(C)C)=O)C=N2)=CC(C(F)(F)F)=C1
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
Soluble in DMSO
Shelf Life
>3 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
Biological target:
KPT-185 is a selective CRM1 inhibitor that induces growth inhibition and apoptosis in a panel of NHL cell lines with a median IC50 ~25 nM.
In vitro activity:
In MCL cells, the small molecule KPT-185 blocks XPO1 function and exerts anti-proliferative effects. This study investigated the molecular mechanisms of this putative anti-tumor effect on MCL cells using cell growth/viability assays, immunoblotting, gene expression analysis, and absolute quantification proteomics. KPT-185 exhibited a p53-independent anti-lymphoma effect on MCL cells, by suppression of oncogenic mediators (e.g., XPO1, cyclin D1, c-Myc, PIM1, and Bcl-2 family members), repression of ribosomal biogenesis, and downregulation of translation/chaperone proteins (e.g., PIM2, EEF1A1, EEF2, and HSP70) that are part of the translational/transcriptional network regulated by heat shock factor 1.
Reference: PLoS One. 2015 Sep 4;10(9):e0137210. https://pubmed.ncbi.nlm.nih.gov/26340096/
|
Solvent |
mg/mL |
mM |
| Solubility |
| Ethanol |
71.0 |
199.82 |
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
355.32
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. Tabe Y, Kojima K, Yamamoto S, Sekihara K, Matsushita H, Davis RE, Wang Z, Ma W, Ishizawa J, Kazuno S, Kauffman M, Shacham S, Fujimura T, Ueno T, Miida T, Andreeff M. Ribosomal Biogenesis and Translational Flux Inhibition by the Selective Inhibitor of Nuclear Export (SINE) XPO1 Antagonist KPT-185. PLoS One. 2015 Sep 4;10(9):e0137210. doi: 10.1371/journal.pone.0137210. PMID: 26340096; PMCID: PMC4560410.
2. Azmi AS, Aboukameel A, Bao B, Sarkar FH, Philip PA, Kauffman M, Shacham S, Mohammad RM. Selective inhibitors of nuclear export block pancreatic cancer cell proliferation and reduce tumor growth in mice. Gastroenterology. 2013 Feb;144(2):447-456. doi: 10.1053/j.gastro.2012.10.036. Epub 2012 Oct 23. PMID: 23089203; PMCID: PMC3594519.
In vitro protocol:
1. Tabe Y, Kojima K, Yamamoto S, Sekihara K, Matsushita H, Davis RE, Wang Z, Ma W, Ishizawa J, Kazuno S, Kauffman M, Shacham S, Fujimura T, Ueno T, Miida T, Andreeff M. Ribosomal Biogenesis and Translational Flux Inhibition by the Selective Inhibitor of Nuclear Export (SINE) XPO1 Antagonist KPT-185. PLoS One. 2015 Sep 4;10(9):e0137210. doi: 10.1371/journal.pone.0137210. PMID: 26340096; PMCID: PMC4560410.
2. Azmi AS, Aboukameel A, Bao B, Sarkar FH, Philip PA, Kauffman M, Shacham S, Mohammad RM. Selective inhibitors of nuclear export block pancreatic cancer cell proliferation and reduce tumor growth in mice. Gastroenterology. 2013 Feb;144(2):447-456. doi: 10.1053/j.gastro.2012.10.036. Epub 2012 Oct 23. PMID: 23089203; PMCID: PMC3594519.
1. Ranganathan, P., Yu, X., Na, C., et al. Preclinical activity of a novel CRM1 inhibitor in acute myeloid leukemia. Blood 120(9), 1765-1773 (2012).
2. Etchin, J., Sanda, T., Mansour, M.R., et al. KPT-330 inhibitor of CRM1 (XPO1)-mediated nuclear export has selective anti-leukaemic activity in preclinical models of T-cell acute lymphoblastic leukaemia and acute myeloid leukaemia. British Journal of Haematology 161(1), 117-127 (2013).
3. Wang, S., Han, X., Wang, J., et al. 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 9(3), e89848 (2014).
