{'fraction_non_alphanumeric': 0.024484536082474227, 'fraction_numerical': 0.012242268041237113, 'mean_word_length': 5.752173913043478, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Selective Kinase Response Modulators (SKRMs), Rho‐iso‐alpha Acids and Tetrahydro‐iso‐alpha acids in inflammation and collagen induced rheumatoid arthritis model in mice

Prostaglandin E2 (PGE2) has been implicated in many inflammatory conditions including osteoarthritis, rheumatoid arthritis, angiogenesis and cancer. Previously we showed that RIAA, a modified hop extract, inhibited NFκB driven COX‐2 expression and PGE2 formation in LPS stimulated RAW 264.7 macrophages. Consistent with these results, we found RIAA inhibited multiple protein kinases involved in LPS induced inflammation. We coined the term Selective Kinase Response Modulators (SKRM) to describe molecules that cooperatively modulate multiple kinases of a given pathway. Shown here, a close analog of RIAA, THIAA was also a potent PGE2 inhibitor with an IC50 2.5x lower. RIAA and THIAA were analyzed in cell free enzyme assays against select protein kinases. Both analogs inhibited multiple kinases in the MAP kinase and B cell receptor (BCR) inflammatory signal transduction pathways; THIAA showed substantially greater inhibition than RIAA. Combinational experiments revealed that THIAA, like RIAA, synergize with rosemary and oleanolic acid to inhibit PGE2 formation in LPS stimulated RAW 264.7 cells. Replacing RIAA with THIAA in a proprietary formula with rosemary and oleanolic acid also showed better inhibition of COX‐2, TNFα and nitric oxide production. These results suggest that THIAA based formulas may have significant therapeutic potential for inflammatory conditions