SMI-4a

製品コードS8005 バッチS800501

印刷

化学情報

Chemical Structure Synonyms TCS PIM-1 4a Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C11H6F3NO2S
分子量 273.23 CAS No. 438190-29-5
Solubility (25°C)* 体外 DMSO 55 mg/mL (201.29 mM)
Ethanol 55 mg/mL (201.29 mM)
Water Insoluble
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 SMI-4a (TCS PIM-1 4a) is a potent inhibitor of Pim1 with IC50 of 17 nM, modestly potent to Pim-2, does not significantly inhibit any other serine/threonine- or tyrosine-kinases.
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]
特徴 SMI-4a (5μM) synergizes with rapamycin (5 nM) to cause significant growth inhibition of leukemic cells.

プロトコル(参考用のみ)

キナーゼアッセイ 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.
動物実験 動物モデル Nu/nu nude mice injected with pre-T-LBL cells
投薬量 60 mg/Kg
投与方法 p.o.

カスタマーフィードバック

, , Blood, 2016, 127:2439-2450.

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Targeting macrophagic PIM-1 alleviates osteoarthritis by inhibiting NLRP3 inflammasome activation via suppressing mitochondrial ROS/Cl- efflux signaling pathway [ J Transl Med, 2023, 21(1):452] PubMed: 37422640
Multicellular immune dynamics implicate PIM1 as a potential therapeutic target for uveitis [ Nat Commun, 2022, 13-1:5866] PubMed: 36195600
Pim1 promotes IFN-β production by interacting with IRF3 [ Exp Mol Med, 2022, 54(11):2092-2103] PubMed: 36446848
Anti-platelet Properties of Pim Kinase Inhibition Is Mediated Through Disruption of Thromboxane A2 Receptor Signalling [ Haematologica, 2020, 28;haematol.2019.223529] PubMed: 32467143
PIM1 inhibition attenuated endotoxin-induced acute lung injury through modulating ELK3/ICAM1 axis on pulmonary microvascular endothelial cells [ Inflamm Res, 2020, 10.1007/s00011-020-01420-3] PubMed: 33185705
Pim-1 as a Therapeutic Target in Lupus Nephritis. [ Arthritis Rheumatol, 2019, 71(8):1308-1318] PubMed: 30791224
PIM1 inhibitor SMI-4a attenuated lipopolysaccharide-induced acute lung injury through suppressing macrophage inflammatory responses via modulating p65 phosphorylation. [ Int Immunopharmacol, 2019, 73:568-574] PubMed: 31203114
The role of dorsal root ganglia PIM1 in peripheral nerve injury-induced neuropathic pain. [ Neurosci Lett, 2019, 709:134375] PubMed: 31349016
Pim1 promotes cell proliferation and regulates glycolysis via interaction with MYC in ovarian cancer [ Onco Targets Ther, 2018, 11:6647-6656] PubMed: 30349298
Palbociclib treatment of FLT3-ITD+ AML cells uncovers a kinase-dependent transcriptional regulation of FLT3 and PIM1 by CDK6 [Uras IZ Blood, 2016, 127(23):2890-902] PubMed: 27099147

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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