For research use only. Not for therapeutic Use.
EMD534085 is a potent and selective inhibitor of the mitotic kinesin-5 with an IC50 of 8 nM.
EMD 534085 does not inhibit any other tested kinesins (BimC, CEN-PE, Chromokinesin, KHC, KIF3C, KIFC3, MKLP-1, and MCAK) at 1 μM or 10 μM concentration, showing selectively over kinesin-5. EMD 534085 binds to the allosteric pocket of kinesin-5[1]. EMD534085 induces rapid cell death in HL60 during mitotic arrest. Caspase-8, −9, −3, −7 are activated; Parp1 is cleaved; Mcl1 and XIAP are degraded in EMD534085-treated HL60 cells. EMD534085 treated HL60 cells also shows significantly accumulated phospho-Histone H3 level starting at 6 hrs post thymidine release[2].
In a low dose PK of EMD 534085 in mice the clearance is 1.8 L/h/kg on average, the volume of distribution is 7.4 L/kg and the half life around 2.5 h. The bioavailability in high dose experiments (>10 mg/kg) is always above 50% in mice. Intraperitonal administration of EMD 534085 enables significant systemic exposure in mice leading to a significant tumor growth
reduction without toxic side effects[1].
| Catalog Number | I006654 |
| CAS Number | 858668-07-2 |
| Synonyms | 1-[[(2R,4aS,5R,10bS)-5-phenyl-9-(trifluoromethyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinolin-2-yl]methyl]-3-[2-(dimethylamino)ethyl]urea |
| Molecular Formula | C25H31F3N4O2 |
| Purity | ≥95% |
| InChI | InChI=1S/C25H31F3N4O2/c1-32(2)13-12-29-24(33)30-15-18-9-10-19-22(16-6-4-3-5-7-16)31-21-11-8-17(25(26,27)28)14-20(21)23(19)34-18/h3-8,11,14,18-19,22-23,31H,9-10,12-13,15H2,1-2H3,(H2,29,30,33)/t18-,19+,22+,23+/m1/s1 |
| InChIKey | MARIUIDCPUZLKZ-FUKQBSRTSA-N |
| SMILES | CN(C)CCNC(=O)NCC1CCC2C(NC3=C(C2O1)C=C(C=C3)C(F)(F)F)C4=CC=CC=C4 |
| Reference | [1]. Schiemann K, et al. The discovery and optimization of hexahydro-2H-pyrano[3,2-c]quinolines (HHPQs) as potent and selective inhibitors of the mitotic kinesin-5. Bioorg Med Chem Lett. 2010 Mar 1;20(5):1491-5. [2]. Tang Y, et al. Rapid induction of apoptosis during Kinesin-5 inhibitor-induced mitotic arrest in HL60 cells. Cancer Lett. 2011 Nov 1;310(1):15-24. |
