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Mussari, Christopher P; Dodd, Dharmpal S; Sreekantha, Ratna Kumar; Pasunoori, Laxman; Wan, Honghe; Posy, Shana L; Critton, David; Ruepp, Stefan; Subramanian, Murali; Watson, Andrew; Davies, Paul; Schieven, Gary L; Salter-Cid, Luisa M; Srivastava, Ratika; Tagore, Debarati Mazumder; Dudhgaonkar, Shailesh; Poss, Michael A; Carter, Percy H; Dyckman, Alaric J
ACS medicinal chemistry letters, 09/2020, Letnik: 11, Številka: 9Journal Article
The toll-like receptor (TLR) family is an evolutionarily conserved component of the innate immune system, responsible for the early detection of foreign or endogenous threat signals. In the context of autoimmunity, the unintended recognition of self-motifs as foreign promotes initiation or propagation of disease. Overactivation of TLR7 and TLR9 have been implicated as factors contributing to autoimmune disorders such as psoriasis, arthritis, and lupus. In our search for small molecule antagonists of TLR7/9, 7f was identified as possessing excellent on-target potency for human TLR7/9 as well as for TLR8, with selectivity against other representative TLR family members. Good pharmacokinetic properties and a relatively balanced potency against TLR7 and TLR9 in mouse systems (systems which lack functional TLR8) made this an excellent in vivo tool compound, and efficacy from oral dosing in preclinical models of autoimmune disease was demonstrated.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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