AZ 3146

Catalog No.S2731

AZ3146 is a selective Mps1 inhibitor with IC50 of ~35 nM, contributes to recruitment of CENP-E (kinesin-related motor protein), less potent to FAK, JNK1, JNK2, and Kit.

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AZ 3146 Chemical Structure

AZ 3146 Chemical Structure
Molecular Weight: 452.55

Validation & Quality Control

Customer Product Validation(2)

Quality Control & MSDS

Related Compound Libraries

AZ 3146 is available in the following compound libraries:

Product Information

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Product Description

Biological Activity

Description AZ3146 is a selective Mps1 inhibitor with IC50 of ~35 nM, contributes to recruitment of CENP-E (kinesin-related motor protein), less potent to FAK, JNK1, JNK2, and Kit.
Targets Mps1 [1]
IC50 ~35 nM
In vitro 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. [1]
In vivo
Features

Protocol(Only for Reference)

Kinase Assay: [1]

In vitro kinase assays For kinase assays, 500 ng His-tagged human Mps1Cat encoding amino acids 510-857 is added to buffer (25 mM Tris-HCl, pH 7.4, 100 mM NaCl, 50 μg/mL BSA, 0.1 mM EGTA, 0.1% β-mercaptoethanol, 10 mM MgCl2, and 0.5 μg/mL myelin basic protein), AZ3146, and 100 μM γ-[32P]ATP (2 μCi/assay). Reactions are incubated at 30°C for 20 minutes, spotted onto P81 paper, washed in 0.5% phosphoric acid, and immersed in acetone. Phosphate incorporation is determined by scintillation counting.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 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 resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Hewitt L, et al. J Cell Biol, 2010, 190(1), 25-34.

Chemical Information

Download AZ 3146 SDF
Molecular Weight (MW) 452.55
Formula

C24H32N6O3

CAS No. 1124329-14-1
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 28 mg/mL (61.87 mM)
Ethanol 91 mg/mL (201.08 mM)
Water <1 mg/mL (<1 mM)
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name 9-cyclopentyl-2-(2-methoxy-4-(1-methylpiperidin-4-yloxy)phenylamino)-7-methyl-7H-purin-8(9H)-one

Customer Product Validation (2)


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Rating
Source J Biol Chem 2013 288(49), 35149-58. AZ 3146 purchased from Selleck
Method Western blot
Cell Lines Hela cells
Concentrations 2 uM
Incubation Time 48 h
Results It have noticed the increase of a faster-migrating BUBR1 species in cell lysates prepared from reversine-treated mitotic HeLa cells, as reported previously. A similar mobility shift was obtained using alternative MPS1 inhibitors SP600125 or AZ3146. The results indicate that BUBR1 phosphorylation may indeed be affected by MPS1 directly or indirectly.

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Rating
Source Oncogenesis 2014 21, 3:e100. AZ 3146 purchased from Selleck
Method MTS/MTA assay
Cell Lines Breast cancer cell lines
Concentrations 0-10 nM
Incubation Time 6 days
Results The specific TTK inhibitor (TTKi) AZ3146 against a panel of breast cancer cell lines and found that TNBC cell lines were more sensitive to the TTKi.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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