LBW242
LBW242, a 3-mer and Smac mimetic, is a potent and orally active proapoptotic IAP inhibitor. LBW242 shows effects on mutant FLT3-expressing cells. LBW242 has activity against multiple myeloma, and potentiates TRAIL- and anticancer agent-mediated cell death of ovarian cancer cells.
For research use only. We do not sell to patients.
- CAS No.: 867324-12-7
- Formula: C27H42N4O2
- Molecular Weight:454.65
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
In Vitro
LBW242 is a 3-mer and Smac mimetic, based on the ability of the NH2-terminal seven amino acids of Smac to neutralize the BIR3 domain of X-chromosome-linked IAP (XIAP). LBW242 partially inhibits the growth of mutant FLT3-expressing lines, MV4;11 at 1 μM[1].
LBW242 kills cells in a manner strictly dependent on caspases, and death is accompanied by PARP cleavage, Annexin positivity, and accumulation of cells in sub-G1[1].
LBW242 (0-0.1 μM; 3 days) inhibits a panel of PKC412-sensitive or PKC412-resistant, mutant FLT3-expressing Ba/F3 lines The IC50 values ranged from 0.5 to >1 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:FLT3-ITD-Ba/F3 cells and mutant FLT3-expressing cells, A627T-FLT3-Ba/F3, F691IFLT3-Ba/F3, and N676D-FLT3-Ba/F3 cells
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Concentration:0.001, 0.01, 0.1 μM
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Incubation Time:3 days
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Result:Inhibited a panel of PKC412-sensitive or PKC412-resistant, mutant FLT3-expressing Ba/F3 lines The IC50 values ranged from 0.5 to >1 μM .
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NCR nude mice were inoculated with FLT3-ITD-Ba/F3 cells[1]
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Dosage:50 mg/kg
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Administration:Oral gavage; daily for 10 days
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Result:Effective in reducing tumor burden.
Chemical Information
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CAS No. 867324-12-7
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Molecular Weight 454.65
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Formula C27H42N4O2
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SMILES
[H][C@@]1(C2)[C@](CCN1C([C@H](C3CCCCC3)NC([C@H](C)NC)=O)=O)([H])CCN2CCC4=CC=CC=C4
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Mammalian live/dead viability and cytotoxicity staining
Live/dead viability and cytotoxicity staining assays are based on the simultaneous detection of intracellular esterase activity in metabolically active (viable) cells and membrane integrity loss in non-viable cells. In commonly used dual-staining approaches, membrane-permeant fluorogenic substrates are converted by intracellular esterases into fluorescent products in live cells, while impermeant DNA-binding dyes selectively enter cells with compromised plasma membranes and label nucleic acids in dead or dying cells, enabling discrimination between viable and non-viable populations by fluorescence microscopy or flow cytometry.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
Purity & Documentation
References
[1]. Weisberg E, et al. Potentiation of antileukemic therapies by Smac mimetic, LBW242: effects on mutant FLT3-expressing cells. Mol Cancer Ther. 2007 Jul;6(7):1951-61. [Content Brief]
[2]. Petrucci E, et al. A small molecule SMAC mimic LBW242 potentiates TRAIL- and anticancer drug-mediated cell death of ovarian cancer cells. PLoS One. 2012;7(4):e35073. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)