product name AZ 3146
Description: AZ3146 is a novel and selective Mps1 inhibitor with IC50 of ~35 nM, it contributes to recruitment of CENP-E (kinesin-related motor protein), and is less potent to FAK, JNK1, JNK2, and Kit. AZ3146 was used to probe the role of Mps1s catalytic activity during mitosis. AZ3146 also inhibits FAK, JNK1, JNK2, KSP and Kit. In in vitro kinase assays, AZ3146 inhibited human Mps1Cat with an IC50 (50% inhibitory concentration) of ~35 nM. AZ3146 also efficiently inhibited autophosphorylation of full-length Mps1 immunoprecipitated from human cells.
References: J Cell Biol. 2010 Jul 12;190(1):25-34.
452.55
Formula
C24H32N6O3
CAS No.
1124329-14-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 28 mg/mL (61.9 mM)
Water: <1 mg/mL
Ethanol: 91 mg/mL (201.1 mM)
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: AZ3146 also inhibits FAK, JNK1, JNK2 and Kit. AZ3146 significantly inhibits phosphorylation of Mps1 in cells. Mitotic-specific phospho forms of aurora B and BubR1 are not affected by AZ3146. AZ3146 does not inhibit Cdk1 or aurora B in mitotic cells. HeLa cells treated with nocodazole and 2 μM AZ3146 only delay mitosis briefly and then rereplicate their genomes, indicating that AZ3146 overrides the SAC. AZ3146 also inhibits an already established SAC signal, as after release from a nocodazole block, AZ3146 dramatically accelerates mitotic exit.During an otherwise unperturbed mitosis, AZ3146 reduces the time to complete mitosis from 90 minutes in controls to 32 minutes. Strikingly, ~90% of AZ3146-treated HeLa cells undergo abnormal mitoses, although ~50% enter anaphase without aligning all of their chromosomes, and ~30% exit mitosis without undergoing obvious chromosome segregation. AZ3146 has a dramatic effect on kinetochore localization of Mad2, reducing its levels to ~15%, but its effect on Mad1 is less pronounced, with levels remaining at ~60%. When Mps1 is inhibited by AZ3146 before mitotic entry, subsequent recruitment of Mad1 and Mad2 to kinetochores is abolished. However, if Mps1 is inhibited by AZ3146 after mitotic entry, the Mad1–C-Mad2 core complex remains kinetochore bound, but O-Mad2 is not recruited to the core. Kinase Assay: Cell Assay: In cellular culture, if Mps1 is inhibited by AZ3146 before mitotic entry, this inhibition abloshed the subsequent recruitment of Mad1 and Mad2 to kinetochores. However, if cells were treated with AZ3146 after mitotic entry, the Mad1-C-Mad2 core complex remains kinetochore bound, but O-Mad2 is not recruited to the core. , AZ3146 interferes with chromosome alignment and overrides spindle assembly checkpoint1. |
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| In Vivo | Regarding the effect of AZ3146 administration in vivo, the evidence should be provided by performing the study in human or mice or other animal models. |
| Animal model | |
| Formulation & Dosage | |
| References | J Cell Biol. 2010 Jul 12;190(1):25-34. |
