EMD534085

Names

[ Name ]:
EMD534085

[Synonym ]:
unii-al67qx8036
Urea, N-[2-(dimethylamino)ethyl]-N'-[[(2R,4aS,5R,10bS)-3,4,4a,5,6,10b-hexahydro-5-phenyl-9-(trifluoromethyl)-2H-pyrano[3,2-c]quinolin-2-yl]methyl]-
1-[2-(Dimethylamino)ethyl]-3-{[(2R,4aS,5R,10bS)-5-phenyl-9-(trifluoromethyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinolin-2-yl]methyl}urea
EMD534085

Biological Activity

[Description]:

EMD534085 is a potent and selective inhibitor of the mitotic kinesin-5 with an IC50 of 8 nM.

[Related Catalog]:

Signaling Pathways >> Cell Cycle/DNA Damage >> Kinesin

Signaling Pathways >> Cytoskeleton >> Kinesin

Research Areas >> Cancer

[Target]

Kinesin-5:8 nM (IC50)

[In Vitro]

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 Vivo]

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 growthreduction without toxic side effects[1].

[Cell Assay]

Epithelial cell lines HeLa and MCF7 are synchronized in G2-phase using RO-3306. Cells are treated with 10 µM RO-3306 for 16 hrs, and then are ished and released to either warm growth medium or medium supplemented with 500 nM EMD534085[2].

[References]

[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.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
609.5±55.0 °C at 760 mmHg

[ Molecular Formula ]:
C₂₅H₃₁F₃N₄O₂

[ Molecular Weight ]:
476.534

[ Flash Point ]:
322.4±31.5 °C

[ Exact Mass ]:
476.239899

[ PSA ]:
69.12000

[ LogP ]:
3.08

[ Vapour Pressure ]:
0.0±1.7 mmHg at 25°C

[ Index of Refraction ]:
1.532

[ Storage condition ]:
2-8℃

Safety Information

[ HS Code ]:
2934999090

Customs

[ HS Code ]: 2934999090

[ Summary ]:
2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%