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Description: CPI-360 is a novel, highly potent, selective, and SAM-competitive inhibitor of enhancer of zeste homolog 2 (EZH2) with potential antitumor activity. It inhibits wt EZH2 and Y641N EZH2 with an IC50 of 0.5 nM and 2.5 nM, respectively. CPI-360 exhibits excellent antiproliferative activity and high in vivo antitumor efficacy. It functions on the basis of S-adenosyl-Lmethionine (SAM)-competition, inhibits EZH1 about 100-fold less and shows exquisite selectivity across a large panel of histone lysine and arginine, and DNA methyltransferases. CPI-360 potently reduced global H3K27me3 and H3K27me2 levels in a dose dependent manner. CPI-360 effectively suppressed heavy H3K27me3 incorporation in KARPAS-422 cells without affecting total histone turnover.
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Physicochemical Properties
| Molecular Formula |
C25H31N3O4
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| Molecular Weight |
437.53
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| Exact Mass |
437.231
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| Elemental Analysis |
C, 68.63; H, 7.14; N, 9.60; O, 14.63
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| CAS # |
1802175-06-9
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| Related CAS # |
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| PubChem CID |
73442743
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| Appearance |
Solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
712.2±60.0 °C at 760 mmHg
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| Flash Point |
384.5±32.9 °C
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| Vapour Pressure |
0.0±2.3 mmHg at 25°C
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| Index of Refraction |
1.621
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
32
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| Complexity |
786
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O1CCC(CC1)[C@@H](C)N1C2C=CC=CC=2C(C(NCC2C(NC(C)=CC=2OC)=O)=O)=C1C
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| InChi Key |
PFPSFENQCNMITC-MRXNPFEDSA-N
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| InChi Code |
InChI=1S/C25H31N3O4/c1-15-13-22(31-4)20(24(29)27-15)14-26-25(30)23-17(3)28(21-8-6-5-7-19(21)23)16(2)18-9-11-32-12-10-18/h5-8,13,16,18H,9-12,14H2,1-4H3,(H,26,30)(H,27,29)/t16-/m1/s1
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| Chemical Name |
N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-2-methyl-1-[(1R)-1-(oxan-4-yl)ethyl]indole-3-carboxamide
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| Synonyms |
| CPI360; CPI 360; CPI-360;(R)-N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(tetrahydro-2H-pyran-4-yl)ethyl)-1H-indole-3-carboxamide |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder-20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Biological Activity
| ln Vitro |
In vitro activity: In KARPAS-422 cells, CPI-360 potently reduces global H3K27me3 and H3K27me2 levels with EC50 of 56 nM and 65 nM, respectively. CPI-360 also causes time-dependent transcriptional changes, and affects the viability of Y641N mutant EZH2-containing KARPAS-422 cells. In addition, CPI-360 gradually arrests KARPAS-422 cells in the G1 cell cycle stage followed by the induction of apoptosis.
Kinase Assay: CPI-360 is a potent, selectiveEZH2inhibitor with IC50 of 0.5 nM and 2.5 nM nM for wt EZH2 and Y641N EZH2, respectively.
Cell Assay: CPI-360 functions on the basis of S-adenosyl-Lmethionine (SAM)-competition, inhibits EZH1 about 100-fold less and shows exquisite selectivity across a large panel of histone lysine and arginine, and DNA methyltransferases. CPI-360 potently reduced global H3K27me3 and H3K27me2 levels in a dosedependent manner. CPI-360 effectively suppressed heavy H3K27me3 incorporation in KARPAS-422 cells without affecting total histone turnover. CPI-360 treatment causes time-dependent transcriptional changes in germinal center B cell-like diffuse large B cell lymphoma. |
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| ln Vivo |
| In mice bearing KARPAS-422 xenografts, CPI-360 (200 mg/kg, s.c.) reduces tumor growth by 44%. |
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| Animal Protocol |
| Dissolved in 10% DMSO + 60% polytheylene glycol 400 + 30% ddH2O; 200 mg/kg; s.c.injection | | Mice bearing KARPAS-422 tumors | |
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| References |
Chem Biol.2014 Nov 20;21(11):1463-75.
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Solubility Data
| Solubility (In Vitro) |
| DMSO: 20 mg/mL (45.7 mM) | | Water:<1 mg/mL | | Ethanol: 18 mg/mL (41.1 mM) |
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| Solubility (In Vivo) |
| 10% DMSO+60% PEG 400+ddH2O:20 mg/mL |
(Please use freshly prepared in vivo formulations for optimal results.)
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| Preparing Stock Solutions |
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1 mg |
5 mg |
10 mg |
| 1 mM |
2.2856 mL |
11.4278 mL |
22.8556 mL |
| 5 mM |
0.4571 mL |
2.2856 mL |
4.5711 mL |
| 10 mM |
0.2286 mL |
1.1428 mL |
2.2856 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles. |
