302561-09-7Relevant articles and documents
Design, Synthesis, and Structure-Activity Relationship of N-Aryl- N′-(thiophen-2-yl)thiourea Derivatives as Novel and Specific Human TLR1/2 Agonists for Potential Cancer Immunotherapy
Chen, Zhipeng,Zhang, Lina,Yang, Junjie,Zheng, Lu,Hu, Fanjie,Duan, Siqin,Nandakumar, Kutty Selva,Liu, Shuwen,Yin, Hang,Cheng, Kui
supporting information, p. 7371 - 7389 (2021/06/28)
The previous virtual screening of ten million compounds yielded two novel nonlipopeptide-like chemotypes as TLR2 agonists. Herein, we present the chemical optimization of our initial hit, 1-phenyl-3-(thiophen-2-yl)urea, which resulted in the identification of SMU-C80 (EC50 = 31.02 ± 1.01 nM) as a TLR2-specific agonist with a 370-fold improvement in bioactivity. Mechanistic studies revealed that SMU-C80, through TLR1/2, recruits the adaptor protein MyD88 and triggers the NF-κB pathway to release cytokines such as TNF-α and IL-1β from human, but not murine, cells. To the best of our knowledge, it is the first species-specific TLR1/2 agonist reported until now. Moreover, SMU-C80 increased the percentage of T, B, and NK cells ex vivo and activated the immune cells, which suppressed cancer cell growth in vitro. In summary, we obtained a highly efficient and specific human TLR1/2 agonist that acts through the MyD88 and NF-κB pathway, facilitating cytokine release and the simultaneous activation of immune cells that in turn affects the apoptosis of cancer cells.
Synthesis of urea analogues bearing N-alkyl-N’-(thiophen-2-yl) scaffold and evaluation of their innate immune response to toll-like receptors
Chen, Zhipeng,Cen, Xiaohong,Yang, Junjie,Lin, Zhiman,Liu, Meihuan,Cheng, Kui
, p. 42 - 52 (2019/03/11)
Previous high throughput virtual screening of 10 million-compound and following cell based validation led to the discovery of a novel, nonlipopeptide-like chemotype ZINC 6662436, as toll-like receptor 2 (TLR2) agonists. In this report, compounds belonging
Pocket-based Lead Optimization Strategy for the Design and Synthesis of Chitinase Inhibitors
Dong, Yawen,Hu, Song,Jiang, Xi,Liu, Tian,Ling, Yun,He, Xiongkui,Yang, Qing,Zhang, Li
, p. 3575 - 3582 (2019/04/01)
Insect chitinases play an indispensable role in shedding old cuticle during molting. Targeting chitinase inhibition is a promising pest control strategy. Of ChtI, a chitinase from the destructive insect pest Ostrinia furnacalis (Asian corn borer), has been suggested as a potential target for designing green pesticides. A 4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate scaffold was previously obtained, and further derivatization generated the lead compound 1 as Of ChtI inhibitor. Here, based on the predicted binding mode of compound 1, the pocket-based lead optimization strategy was applied. A series of analogues was synthesized, and their inhibitory activities against Of ChtI were evaluated. Compound 8 with 6-tert-pentyl showed preferential inhibitory activity with a Ki value of 0.71 μM. Their structure-activity relationships suggested that the compound with larger steric hindrance at the 6-nonpolar group was essential for inhibitory activity due to its stronger interactions with surrounding amino acids. This work provides a strategy for designing potential chitinase inhibitors.
ANTHELMINTIC AND INSECTICIDAL THIOPHENE DERIVATIVES
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Page 19-20, (2008/06/13)
Novel anthelmintic compositions containing thiophene derivatives as active ingredients are disclosed.
