EMD534085 is a potent and selective inhibitor of the mitotic kinesin-5 with an IC50 of 8 nM. 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.
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 growth reduction without toxic side effects.
| Cell Experiment | |
|---|---|
| Cell lines | Epithelial cell lines HeLa and MCF7 |
| Preparation method | 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. |
| Concentrations | 500 nM |
| Incubation time | |
| Animal Experiment | |
|---|---|
| Animal models | |
| Formulation | |
| Dosages | |
| Administration | |
| Molecular Weight | 476.53 |
| Formula | C25H31F3N4O2 |
| CAS Number | 858668-07-2 |
| Solubility (25°C) | DMSO: ≥ 20 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related Kinesin Products |
|---|
| Eg5-IN-1
Eg5-IN-1 is a potent kinesin family motor protein (Eg5) inhibitor with an IC50 value of 1.97 µM. |
| PVZB-1194
PVZB-1194 is a biphenyl-type inhibitor of kinesin Eg5 that induces apoptosis by inhibiting Eg5 ATPase activity and shows potent kinesin spindle protein (KSP) inhibition only in the presence of microtubules, with anticancer activity. |
| Litronesib
Litronesib (LY2523355) is a selective mitosis-specific kinesin Eg5 inhibitor, with antitumor activity. |
| MK-0731
MK-0731 is a selective, non-competitive and allosteric kinesin spindle protein (KSP) inhibitor with an IC50 of 2.2 nM and a pKa of 7.6. MK-0731 is >20,000 fold selectivity against other kinesins. MK-0731 induces mitotic arrest and induces apoptosis in tumors. MK-0731 provides significant antitumor efficacy. |
| BRD9876
BRD9876 is the “rigor” inhibitor that locks kinesin-5 (Eg5) in a state with enhanced microtubules (MTs) binding, leading to bundling and stabilization of MTs. BRD9876 interacts with the tyrosine 104 residue that is part of the α4-α6 allosteric binding pocket. BRD9876 specifically targets microtubule-bound Eg5 and selectively inhibits myeloma over CD34 cells. BRD9876 has the potential for multiple myeloma (MM) research. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.
