Antibodies
SMI-4a
- 貨號 Cat. No.
- S8005
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
SMI-4a
Catalog No.S8005
SMI-4a is a potent inhibitor of Pim1 with IC50 of 17 nM, modest potent to Pim-2, does not significantly inhibit other serine/threonine- or tyrosine-kinases.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | SMI-4a is a potent inhibitor of Pim1 with IC50 of 17 nM, modest potent to Pim-2, does not significantly inhibit other serine/threonine- or tyrosine-kinases. | |||||
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| Targets | Pim1 | |||||
| IC50 | 17 nM[1] | |||||
| In vitro | SMI-4a is an ATP competitive inhibitor of Pim1 with IC50 of 17 nM. SMI-4a shows high selectivity for Pim1 against a panel of kinases. SMI-4a inhibits the in vitro phosphorylation by Pim-1 of the known substrate, the translational repressor 4E-BP1. SMI-4a (5μM) inhibits pancreatic and leukemic cells growth. SMI-4a reduces phosphorylation of the Pim target Bad in prostate and hematopoietic cells. SMI-4a causes cell cycle arrest and reverses the antiapoptotic activity of Pim-1. SMI-4a increases the amount of p27Kip1 in the nucleus.[1] SMI-4a treatment of pre-T-LBL inhibits the mTOR pathway. SMI-4a reduces MYC protein expression in pre-T-LBL. SMI-4a treatment induces up-regulation of MAPK pathway. [2] | |||||
| In vivo | SMI-4a (60 mg/Kg) treatment twice daily significantly reduce tumor size and is well tolerated. Tumors harvested 1 hour after the final oral gavage of SMI-4a demonstrates decreased phosphorylation of p70 S6K compared with tumors from mice treated with vehicle, whereas in comparison total p70 S6K expression isunchanged. [2] | |||||
| Features | SMI-4a (5μM) synergizes with rapamycin (5 nM) to cause significant growth inhibition of leukemic cells. | |||||
Protocol(Only for Reference)
Kinase Assay: [1]
| Kinase Activity Assay | IC50 values for Pim inhibitors are measured by a coupled kinase assay as described previously with the following changes: assays are carried out in 20 mM MOPS containing 100 mM NaCl, 10 mM MgCl2, 2.5 mM phosphoenolpyruvate, 0.2 mM NADH, 30μg/mL pyruvate kinase, 10μg/mL lactate dehydrogenase, 2 mM DTT, and 25 nM Pim-1 with 100μM peptide. Activity ismeasured by monitoring NADH oxidation as the decrease at 340 nm in a VersaMax microplate reader at 25 ℃. Reactions are initiated by the addition of ATP (100 μM), and inhibitors (final 1% DMSO) are added just before the addition of ATP. IC50 values are determined using nonlinear regression with the program GraphPad Prism. This assay determines kinase activity by measuring the amount of ADP produced, which is coupled to NADH oxidation by lactate dehydrogenase and pyruvate kinase. The ability of Pim-1 kinase to phosphorylate full-length protein substrates 4E-BP1 and p27Kip1 isdetermined as follows: purified Pim-1 (1 ng) isadded along with 4E-BP1 (2 μg) or p27Kip1 (2 μg) and Pim inhibitor in assay buffer [20 mM MOPS (pH 7) containing 100 mM NaCl, 10 mM MgCl2, and 2 mM DTT]. Assays are initiated by the addition of ATP (100 μM) and [γ-32P]ATP (10 μCi). Reactions are allowed to proceed for 15 min at 30℃ and then separated by SDS-PAGE. 32P-phosphorylated substrates are visualized by autoradiography and quantified by densitometry. |
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Animal Study: [2]
| Animal Models | Nu/nu nude mice injected with pre-T-LBL cells |
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| Dosages | 60 mg/Kg |
| Administration | p.o. |
| Solubility | 30% PEG400/0.5% Tween80/5% propylene glycol, 30 mg/mL |
References
Chemical Information
| Molecular Weight (MW) | 273.23 |
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| Formula | C11H6F3NO2S |
| CAS No. | 438190-29-5 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 55 mg/mL (201 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | 32 mg/mL (117 mM) | ||
| In vivo | 30% PEG400/0.5% Tween80/5% propylene glycol, | 30 mg/mL | |
| * <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 | 2,4-Thiazolidinedione, 5-[[3-(trifluoromethyl)phenyl]methylene]-, (5Z)- |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
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| Mass(mg) | 0.27323 | 2.7323 | 5.4646 | 8.1969 |
