| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
|
Purity: ≥98%
Description: BAY-524 is a novel and potent Bub1 inhibitor with an IC50 of 450 nM for human Bub1 in the presence of 2 mM ATP. It demonstrated potent Bub1 kinase inhibition both in vitro and in intact cells. The kinase Bub1 functions in the spindle assembly checkpoint (SAC) and in chromosome congression, but the role of its catalytic activity remains controversial. Bub1 inhibition affected chromosome association of Shugoshin and the chromosomal passenger complex (CPC), without abolishing global Aurora B function. Consequently, inhibition of Bub1 kinase impaired chromosome arm resolution but exerted only minor effects on mitotic progression or SAC function. Importantly, BAY-320 and BAY-524 treatment sensitized cells to low doses of Paclitaxel, impairing both chromosome segregation and cell proliferation. These findings are relevant to our understanding of Bub1 kinase function and the prospects of targeting Bub1 for therapeutic applications.
| ln Vitro |
At an IC50 of 450 nM, BAY-524 inhibits the human Bub1 recombinant catalytic domain[1]. BAY-524 selectively inhibits Bub1 kinase at 7–10 μM or 0–30 μM for 14 hours or 1 hour [1]. The effects of BAY-524 (7 μM, 12 hours or 7 μM, 12 μM, 3 hours) on chromatid cohesion and Sgo1 and Sgo2 localization in cells have been reported [1]. BAY-524 (7 μM, 10 μM) modifies CPC's activity and localization [1]. Additive effects on CPC centromere association are observed with BAY-524 (7 μM, 2 h) [1]. There is a slight impact of BAY-524 (7 μM, 48 hours) on SAC signaling [1]. Cells are sensitized to low doses of paclitaxel by BAY-524 (7 μM, 10 μM) [1].
|
|---|---|
| Cell Assay |
Western Blot Analysis[1]
Cell Types: hTERT-RPE1 (RPE1) and HeLa cells Tested Concentrations: 7-10 μM Incubation Duration: 14 hrs (hours) Experimental Results: Significant reduction in T120 phosphorylation. Immunofluorescence[1] Cell Types: RPE1 and HeLa cells Tested Concentrations: 0-30 μM Incubation Duration: 1 hour Experimental Results: diminished phosphorylation of histone H2A-T120. |
| References |
| Molecular Formula |
C24H24F2N6O3
|
|---|---|
| Molecular Weight |
482.48
|
| Exact Mass |
482.187
|
| CAS # |
1445830-39-6
|
| PubChem CID |
71611179
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
3.8
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
35
|
| Complexity |
636
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
FC1C([H])=C(C([H])=C(C=1C([H])([H])N1C(=C(C([H])([H])[H])C(C2=NC([H])=C(C(N([H])C3C([H])=C([H])N=C([H])C=3[H])=N2)OC([H])([H])[H])=N1)OC([H])([H])[H])F)OC([H])([H])C([H])([H])[H]
|
| InChi Key |
LMRCQVHTZUUHFN-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C24H24F2N6O3/c1-5-35-16-10-18(25)17(19(26)11-16)13-32-24(34-4)14(2)21(31-32)23-28-12-20(33-3)22(30-23)29-15-6-8-27-9-7-15/h6-12H,5,13H2,1-4H3,(H,27,28,29,30)
|
| Chemical Name |
2-[1-[(4-ethoxy-2,6-difluorophenyl)methyl]-5-methoxy-4-methylpyrazol-3-yl]-5-methoxy-N-pyridin-4-ylpyrimidin-4-amine
|
| Synonyms |
BAY-524; BAY 524; BAY524
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~166.67 mg/mL (~345.44 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.17 mg/mL (8.64 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 41.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 4.17 mg/mL (8.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 41.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0726 mL | 10.3631 mL | 20.7262 mL | |
| 5 mM | 0.4145 mL | 2.0726 mL | 4.1452 mL | |
| 10 mM | 0.2073 mL | 1.0363 mL | 2.0726 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
BAY-320 and BAY-524 inhibit Bub1 kinase.Elife. 2016 Feb 17;5. pii: e12187. |
Inhibition of Bub1 affects Sgo1 and Sgo2 localization and chromatid cohesion.Elife. 2016 Feb 17;5. pii: e12187. |
Bub1 inhibition affects localization and activity of the CPC.Elife. 2016 Feb 17;5. pii: e12187. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
