524619

PIP3 Antagonist II, DM-PIT-1

The PIP3 Antagonist II, DM-PIT-1, also referenced under CAS 701947-53-7, controls the biological activity of PIP3.

• Synonyme(s) : PIP3 Antagonist II, DM-PIT-1, N-​(((2-Hydroxy-​5-​nitrophenyl)amino)thioxomethyl)-​3,​5-​dimethyl-​benzamide, N-((2-Hydroxy-5-nitrophenyl)carbamothioyl)-3,5-dimethylbenzamide, Akt Inhibitor XXII, PDK1 Inhibitor VI
• Formule empirique (notation de Hill): C₁₆H₁₅N₃O₄S
• Numéro CAS: 701947-53-7
• Poids moléculaire : 345.37
• Numéro MDL: MFCD05129220
• Code UNSPSC : 12352200
• Nomenclature NACRES : NA.51

Propriétés

• Niveau de qualité: 100
• Pureté: ≥98% (HPLC)
• Forme: powder
• Fabricant/nom de marque: Calbiochem^®
• Conditions de stockage: OK to freeze; protect from light
• Couleur: off-white
• Solubilité: DMSO: 25 mg/mL
• Conditions d'expédition: ambient
• Température de stockage: 2-8°C
• Chaîne SMILES: OC(C=CC([N+]([O-])=O)=C1)=C1NC(NC(C2=CC(C)=CC(C)=C2)=O)=S

Description

Description générale

A cell-permeable benzoylthiourea compound that is shown to compete against PIP3 (Cat. No. 524615) for binding PH (pleckstrin-homology) domains of Akt1 (IC₅₀ ≥31 µM using recombinant human Akt1 aa 1-123), ARNO, GRP1, and PKD1, while lacking activity against PIP3 Btk PH domain ineraction, PI-4,5-P2 (Cat. Nos. 524614, 524644, and 524646) PLC-δ PH domain binding, or PI-3,4-P2 TAPP1/2 PH domains binding, resulting in effective blockage of PIP3-dependent PI3K-PDK1-Akt signaling pathway activation in human glioblastoma U87MG cultures (25 to 100 µM for 3 d) and (5 min 100 ng/ml) PDGF-induced Akt and GRP membrane translocation (by 85% and 70%, respectively, with 1 h 100 µM pretreatment) in serum-starved human breast cancer SUM159 cells, while being inactive against PDGF-induced Btk translocation or (5 min 250 ng/ml) PMA-induced PLC-δ and TAPP1/2 translocations. Although DM-PIT-1 can be administered as a DMSO stock for effective culture treatments, incorporating DM-PIT-1 into PEG-PE mixed micelles is reported to enhance its solubility (up to 1 mM), and presumably delivery efficiency (57% vs. 67% U87MG viability after 24 h 50 µM drug treatment, respectively, with or without PEG-PE encapsulation), making large dosage delivery possible for more effective in vivo administrations (5% vs. 41% of control 4T1 tumor size in mice after 8 daily i.v. dosages of 1 mg/kg micelles-formulated or 0.4 mg/kg free drug, respectively).

A cell-permeable benzoylthiourea compound that is shown to compete against PIP3 (Cat. No. 524615) for binding PH domains of Akt1 (IC₅₀ ≥31 µM), ARNO, GRP1, and PKD1. Effectively blocks PIP3-dependent cellular PI3K-PDK1-Akt signaling pathway activation in U87MG (25 to 100 µM for 3 d) and PDGF-induced Akt and GRP membrane translocation in serum-starved SUM159 cells (1 h 100 µM pretreatment), while being inactive against PDGF-induced Btk translocation or PMA-induced PLC-δ and TAPP1/2 translocations. Although DM-PIT-1 can be administered as a DMSO stock for effective culture treatments, incorporating DM-PIT-1 into PEG-PE mixed micelles enhances its solubility (up to 1 mM) and i.v. dosing limit for more effective in vivo administrations (5% vs. 41% of control 4T1 tumor size in mice via 1 mg/kg micelles-formulated or 0.4 mg/kg free drug daily i.v., respectively).

Conditionnement

Packaged under inert gas

Avertissement

Toxicity: Regulatory Review (Z)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Autres remarques

Miao, B., et al. 2010. Proc. Natl. Acad. Sci. USA107, 20126.
Skidan, I., et al. 2009. Drug Deliv.16, 45.

Informations légales

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Informations sur la sécurité

• Code de la classe de stockage: 11 - Combustible Solids
• Classe de danger pour l'eau (WGK): WGK 3
• Point d'éclair (°F): Not applicable
• Point d'éclair (°C): Not applicable