| Identification | Back Directory | [Name]
3,5-dimethyl PIT-1 | [CAS]
701947-53-7 | [Synonyms]
DM-PIT-1
3,5-dimethyl PIT-1
DM-PIT-1
(3,5-dimethyl PIT-1)
3,5 dimethyl PIT 1,3,5dimethyl PIT1
PIP3 Antagonist II, DM-PIT-1 - CAS 701947-53-7 - Calbiochem
N-[(2-hydroxy-5-nitrophenyl)carbamothioyl]-3,5-dimethylbenzamide
Benzamide, N-[[(2-hydroxy-5-nitrophenyl)amino]thioxomethyl]-3,5-dimethyl- | [Molecular Formula]
C16H15N3O4S | [MOL File]
701947-53-7.mol | [Molecular Weight]
345.37 |
| Chemical Properties | Back Directory | [storage temp. ]
+2C to +8C | [solubility ]
DMF:30.0(Max Conc. mg/mL);86.86(Max Conc. mM)
DMF:PBS (pH 7.2) (1:1):0.5(Max Conc. mg/mL);1.45(Max Conc. mM)
DMSO:20.0(Max Conc. mg/mL);57.91(Max Conc. mM)
Ethanol:0.2(Max Conc. mg/mL);0.58(Max Conc. mM) | [form ]
Off-white powder | [color ]
off-white | [InChI]
1S/C16H15N3O4S/c1-9-5-10(2)7-11(6-9)15(21)18-16(24)17-13-8-12(19(22)23)3-4-14(13)20/h3-8,20H,1-2H3,(H2,17,18,21,24) | [InChIKey]
CGWBCAQMXJFWBU-UHFFFAOYSA-N | [SMILES]
OC(C=CC([N+]([O-])=O)=C1)=C1NC(NC(C2=CC(C)=CC(C)=C2)=O)=S |
| Hazard Information | Back Directory | [Description]
PtdIns-(3,4,5)-P3 (PIP3) serves as an anchor for the binding of signal transduction proteins bearing pleckstrin homology (PH) domains such as phosphatidylinositol 3-kinase (PI3K) or PTEN. Protein binding to PIP3 is important for cytoskeletal rearrangement and membrane trafficking and initiates an intricate signaling cascade that has been implicated in cancer. 3,5-dimethyl PIT-1 is a dimethyl analog of PIT-1, the selective inhibitor of PIP3/Akt PH domain binding, that is designed for more favorable solubility in vivo. 3,5-dimethyl PIT-1 inhibits PI3K/Akt signaling (IC50 = 27 μM), suppressing PI3K-PDK1-Akt-dependent phosphorylation, which has been shown to reduce cell viability and induce apoptosis in PTEN-deficient U87MG glioblastoma cells (IC50 = 36 μM). 4T1 breast cancer growth is significantly attenuated in BALB/c mice with a dose of 1 mg/kg of 3,5-dimethyl PIT-1 per day. | [Uses]
DM-PIT-1 is a PIP3/PH (phosphatidylinositol-3,4,5-triphosphate/Pleckstrin) interaction inhibitor. DM-PIT-1 decreases he expression of P-Akt, P-GSK-3-β, P-p70S6K, P-S6, P-4E-BP1. DM-PIT-1 induces apoptosis and shows anticancer activity. DM-PIT-1 has the potential for the research of ovarian cancer[1][2]. | [General Description]
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). | [in vivo]
DM-PIT-1 (0.4 mg/kg; i.v.; daily for 8 days) shows anti-tumor activity in 4T1 breast cancer model[2]. | [References]
[1] Riehle RD, et al. Micellar formulations of pro-apoptotic DM-PIT-1 analogs and TRAIL in vitro and in vivo. Drug Deliv. 2013 Feb;20(2):78-85. DOI:10.3109/10717544.2013.766780 |
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