1-NM-PP1 (Synonyms: PP1 Analog II) |
| رقم الكتالوجGC11696 |
1-NM-PP1 ، تناظري PP1 قابل للنفاذ للخلايا ، هو مثبط قوي لإنزيمات عائلة Src مع IC50s 4.3 نانومتر و 3.2 نانومتر لـ v-Src-as1 و c-Fyn-as1 ، على التوالي
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 221244-14-0
Sample solution is provided at 25 µL, 10mM.
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1-NM-PP1 is a C3-modified analog of cell-permeable PP1, acts as a potent and selective inhibitor of protein kinase families [1].
1-NM-PP1 has shown the selective inhibition of protein kinases that have been mutated with the IC50 values of 28 μM, 1.0 μM, 3.4 μM, 29 μM, 24 μM,4.3 nM, 3.2 nM, 120 nM,5 nM and 8 nM for v-Src, c-Fyn, c-Abl, CDK2, CAMKII, v-Src-as1, c-Fyn-as1, cAbl-as2, CDK2-as1 and CAMKII-as1, respectively. 1-NM-PP1 inhibited each of the five target kinases at low nanomolar concentrations with target-specificities ranging from 85-fold to 400-fold measured against the most inhibitable wild-type kinases. In addition, the in vitro study has also revealed that Cdc28-as1 is highly sensitive to 1-NM-PP1 with ATP kinetic Km values of 35 μM and 322 μM, the Kcat values of 132 min-1 and 21.3 min-1, the Kcat/Km values of 3.7 and 0.066, the IC50 values of 22 μM and 0.002 μM for Cdc28/Clb2 and Cdc28-as1/Clb2, respectively [1].
References:
[1] Bishop AC1, Ubersax JA, Petsch DT, Matheos DP, Gray NS, Blethrow J, Shimizu E, Tsien JZ, Schultz PG, Rose MD, Wood JL, Morgan DO, Shokat KM. A chemical switch for inhibitor-sensitive alleles of any protein kinase. Nature. 2000 Sep 21; 407(6802):395-401.
| Kinase experiment [1]: | |
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In vitro kinase assays |
We carried out in vitro kinase assays (except for Cdc28) in the presence of 0.2 μCi /μl [γ-32P]ATP at low ATP concentration (10 nM) so that IC50 values represent a rough measure of the inhibition constant (Ki). Measurement of inhibitor IC50 values were done as Liu, Y. et al. described. Purified Cdc28–His6 (1 nM) and MBP–Clb2 (3 nM) were incubated for 10 min at 23℃ in a 25 μl reaction mixture containing 5 μg histone H1, 1 μCi of [γ-32P]ATP (1 μCi per 10 μM and 1μCi per 1 mM), and varying concentrations of 1-NM-PP1 in kinase buffer (25mM HEPES-NaOH pH 7.4, 10mM NaCl, 10mM MgCl2 and 1mM dithiothreitol). Reaction products were analysed by 15% SDS–PAGE followed by autoradiography. For the determination of Cdc28 kinetic constants, varying concentrations of [γ-32P]ATP (1 μCi per 100 μM) were incubated and analysed as above. |
| Cell experiment [2]: | |
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Cell lines |
PDK1?/? ES cells |
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Preparation method |
This compound is soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
10 μM for 24h-72h; or 20 μM for 48h |
|
Applications |
1-NM-PP1 suppressed the phosphorylation of PDK1 targets in PDK1?/? ES cells expressing PDK1 L159G but not WT PDK1. Moreover, 1-NM-PP1 inhibited sorbitol-induced MSK1 S212 T-loop phosphorylation, ERK/p38MAPK phosphorylation sites S581 and ERK/p38 dependent autophosphorylation at S376. 1-NM-PP1 also inhibited IGF1-stimulated PKB/Akt T308 phosphorylation and S6K activity in PDK1?/? +LG ES cells. |
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References: 1. Bishop, A. C., Ubersax, J. A., Petsch, D. T., Matheos, D. P., Gray, N. S., Blethrow, J., Shimizu, E., Tsien, J. Z., Schultz, P. G., Rose, M. D., Wood, J. L., Morgan, D. O. and Shokat, K. M. (2000) A chemical switch for inhibitor-sensitive alleles of any protein kinase. Nature. 407, 395-401 2. Tamguney, T., Zhang, C., Fiedler, D., Shokat, K. and Stokoe, D. (2008) Analysis of 3-phosphoinositide-dependent kinase-1 signaling and function in ES cells. Exp Cell Res. 314, 2299-2312 | |
| Cas No. | 221244-14-0 | SDF | |
| المرادفات | PP1 Analog II | ||
| Chemical Name | 1-tert-butyl-3-(naphthalen-1-ylmethyl)pyrazolo[3,4-d]pyrimidin-4-amine | ||
| Canonical SMILES | CC(C)(C)N1C2=C(C(=N1)CC3=CC=CC4=CC=CC=C43)C(=NC=N2)N | ||
| Formula | C20H21N5 | M.Wt | 331.41 |
| الذوبان | ≥ 16.55mg/mL in DMSO, ≥ 9.22 mg/mL in EtOH with ultrasonic and warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0174 mL | 15.0871 mL | 30.1741 mL |
| 5 mM | 0.6035 mL | 3.0174 mL | 6.0348 mL |
| 10 mM | 0.3017 mL | 1.5087 mL | 3.0174 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 18 reference(s) in Google Scholar.)
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