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Similar to previous protocol, we carried out tandem affinity purification and analyzed the protein complexes using negative stain electron microscopy, which exhibits a comparable dimeric architecture (Supplementary Fig

Inactivated NF-B is present as a cytoplasmic heterodimer, which consists of the P65 and P50 subunits, and can bind to the inhibitory protein IB

These effects appear to be mediated primarily through activation of phosphodiesterase 3B (138)

The compounds work differently enough that direct dose translation is not valid

The Phase 2 trial enrolled participants with obesity and evaluated multiple dose levels over 48 weeks: 1 mg dose: 8.7% average body weight reduction 4 mg dose (escalated from 2 mg): 17.1% average body weight reduction 8 mg dose (escalated from 2 mg): 22.8% average body weight reduction 12 mg dose (escalated from 2 mg): 24.2% average body weight reduction Placebo: 2.1% average body weight reduction Those Phase 2 numbers were striking enough