ML141 (also called CID-2950007; ML-141; CID2950007; ML 141) is a novel potent, selective and reversible non-competitive inhibitor of Rho family GTPase cdc42 with potential anticancer activity. It inhibits cdc42 with an IC50 of 200 nM. ML141 enhances the ability of TMX to suppress BLBC cell growth through both induction of cell death and suppression of cell division. ML141 also significantly protects neuroblastoma cells from metformin-induced apoptosis. Moreover, ML141 diminishes K. pneumoniae invasion in a dose-dependent manner.
理化性质和储存条件
| Molecular Weight (MW) | 407.49 |
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| Formula | C22H21N3O3S |
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| CAS No. | 71203-35-5 |
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| Storage | -20℃ for 3 years in powder form |
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| -80℃ for 2 years in solvent |
| Solubility (In vitro) | DMSO: 81 mg/mL (198.8 mM) |
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| Water: <1 mg/mL |
| Ethanol: <1 mg/mL |
| Solubility (In vivo) | 2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 10mg/mL |
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| Synonyms | CID-2950007; ML-141; CID2950007; ML 141; CID 2950007; ML141 |
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实验参考方法
| In Vitro | In vitro activity: ML141 enhances the ability of TMX to suppress BLBC cell growth through both induction of cell death and suppression of cell division. ML141 also significantly protects neuroblastoma cells from metformin-induced apoptosis. Moreover, ML141 diminishes K. pneumoniae invasion in a dose-dependent manner.
Kinase Assay: Wild-type GST-Cdc42 (4 μM) is bound to GSH-beads overnight at 4°C. Cdc42 on GSH-beads is depleted of nucleotide by incubating with 10 mM EDTA containing buffer for 20 min at 30°C, washing twice with NP- HPS buffer, then re-suspended in the same buffer containing 1 mM EDTA/or 1 mM MgCl2, 1 mM DTT and 0.1% BSA. Cdc42 unbound sites are blocked by incubation of protein–bead complex for 15 min at RT. Thirty μL of this suspension is incubated with 20 mM inhibitor for 3 min at RT and added 30 μL of various concentrations of ice cold BODIPY-FL-GTP. Samples incubated at 4° C for 45 min and binding of fluorescent nucleotide to enzyme is measured using an Accuri flow cytometer. Raw data are exported and plotted using GraphPad Prism software.
Cell Assay: Cells [Basal-B (MDA-MB 231 and HCC38) and Basal-A with HER2 amplification (HCC1954) cells] are incubated with 500 nM Calcein-AM and 1 μM PI for 15 min, after which live cells and dead cells (represented by positivity of Calcein-AM and PI staining, respectively) are counted utilizing the adherent cell Celigo(TM) cytometer. |
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| In Vivo | In NOD/SCID mice bearing MDA-MB 231 derived tumors, ML141 (1 mg/day i.p.), via inhibition of Cdc42, enables TMX to suppress growth of MDA-MB 231 derived tumors. In addition, ML141 (10 mg/kg i.p.) enhances G-CSF-induced hematopoietic stem and progenitor cell mobilization in mice. |
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| Animal model | NOD/SCID mice bearing MDA-MB 231 derived tumors |
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| Formulation & Dosage | Dissolved in Corn oil; 1 mg/kg daily; i.p. injection |
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| References | Oncotarget. 2014 Nov 30;5(22):11709-22; EMBO Mol Med. 2013 May;5(5):723-36. |
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