| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
CDK2 (IC50 = 200 nM); PKC
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|---|---|
| ln Vitro |
Bisindolylmaleimide X hydrochloride (BIM-X hydrochloride; Ro31-8425 hydrochloride) derivatives are effective instruments for evaluating inhibitor potency and target selectivity [1].
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| References | |
| Additional Infomation |
Bisindolylmaleimide compounds, such as GF109203X, are potent inhibitors of protein kinase C (PKC) activity. Although bisindolylmaleimide compounds are not entirely selective in inhibiting PKC and are known to inhibit other protein kinases as well, they have been widely used for over a decade to study the functional roles of PKC family enzymes in cell signal transduction. This paper establishes a proteomics approach to further understand the cellular effects of these compounds. By functionally immobilizing suitable bisindolylmaleimide analogs and combining this with affinity chromatography to specifically purify cell-binding proteins, we identified several known and previously unknown enzyme targets. Subsequent in vitro binding and activity assays confirmed that protein kinases Ste20-associated kinase and cyclin-dependent kinase 2 (CDK2), as well as non-protein kinases adenosine kinase and quinone reductase type 2, are novel targets for bisindolylmaleimide inhibitors. As observed in CDK2, small chemical changes in the ligands significantly affected their binding to the target by immobilizing structurally related bisindolylmaleimide III, VIII, and X. These observed affinity changes were correlated with the IC50 values of CDK2 inhibition in vitro and the results of molecular docking to CDK2 crystal structures. Furthermore, by adjusting affinity purification conditions, immobilized bisindolylmaleimide III could selectively interact with the target only after activation of PKCα or ribosomal S6 protein kinase 1. Thus, we established an efficient technique for rapid identification of cellular bisindolylmaleimide targets and further demonstrated comparative selectivity analysis of closely related kinase inhibitors in the cellular proteome. [1]
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| Molecular Formula |
C26H25CLN4O2
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|---|---|
| Molecular Weight |
460.9553
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| Exact Mass |
460.166
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| Elemental Analysis |
C, 67.75; H, 5.47; Cl, 7.69; N, 12.15; O, 6.94
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| CAS # |
145317-11-9
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| PubChem CID |
11539879
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| Appearance |
Light yellow to orange solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
33
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| Complexity |
825
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl[H].O=C1C(=C(C(N1)=O)C1=CN(C)C2=CC=CC=C12)C1C2=CC=CC=C2N2CCC(CN)CC2=1
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| InChi Key |
IMBOYWXMTUUYGZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H24N4O2.ClH/c1-29-14-18(16-6-2-4-8-19(16)29)23-24(26(32)28-25(23)31)22-17-7-3-5-9-20(17)30-11-10-15(13-27)12-21(22)30;/h2-9,14-15H,10-13,27H2,1H3,(H,28,31,32);1H
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| Chemical Name |
3-[8-(aminomethyl)-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione;hydrochloride
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| Synonyms |
Ro-31-8425; 145317-11-9; Ro 31-8425; Ro31-8425;Bisindolylmaleimide X hydrochloride; bisindolylmaleimide x; Bisindoylmaleimide X HCl; Bisindolylmaleimide X (hydrochloride); Bisindolylmaleimide X HCl; 1H-Pyrrole-2,5-dione, 3-[8-(aMinoMethyl)-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]-4-(1-Methyl-1H-indol-3-yl)-, Monohy; Ro 318425;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~20.83 mg/mL (~45.19 mM)
H2O : < 0.1 mg/mL |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.51 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1694 mL | 10.8469 mL | 21.6939 mL | |
| 5 mM | 0.4339 mL | 2.1694 mL | 4.3388 mL | |
| 10 mM | 0.2169 mL | 1.0847 mL | 2.1694 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.
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