Structure-Based Discovery of Novel Chemical Classes of Autotaxin Inhibitors
نویسندگان
چکیده
منابع مشابه
Chemical Evolution of Autotaxin Inhibitors
(ATX or ENPP2) was isolated as an autocrine motility factor from melanoma cells. 1 The ∼120 kDa glycoprotein ATX belongs to a small family named ectonucleotide pyrophosphatase and phosphodiesterase (ENPP), which consists of seven family members. 2 ATX is the only ENPP family member with lysophospholipase D (lysoPLD) activity and is responsible for the hydrolysis of lysophosphatidylcholine (LPC)...
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Autotaxin (ATX) is a secreted phosphodiesterase that hydrolyzes the abundant phospholipid lysophosphatidylcholine (LPC) to produce lysophosphatidic acid (LPA). The ATX-LPA signaling axis has been implicated in inflammation, fibrosis, and tumor progression, rendering ATX an attractive drug target. We recently described a boronic acid-based inhibitor of ATX, named HA155 (1). Here, we report the d...
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In an effort to develop a novel therapeutic agent aimed at addressing the unmet need of patients with osteoarthritis pain, we set out to develop an inhibitor for autotaxin with excellent potency and physical properties to allow for the clinical investigation of autotaxin-induced nociceptive and neuropathic pain. An initial hit identification campaign led to an aminopyrimidine series with an aut...
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A new chemical series, triazolo[4,5-b]pyridines, has been identified as an inhibitor of PIM-1 by a chemotype hopping strategy based on a chemically feasible fragment database. In this case, structure-based virtual screening and in silico chemogenomics provide added value to the previously reported strategy of prioritizing among proposed novel scaffolds. Pairwise comparison between compound 3, r...
متن کاملساختار کلاسهایی از حلقه های z- موضعی و c- موضعی the structure of some classes of z-local and c-local rings
فرض کنیمr یک حلقه تعویض پذیر ویکدار موضعی باشدو(j(r رایکال جیکوبسن r و(z(r مجموعه مقسوم علیه های صفر حلقه r باشد.گوییم r یک حلقه z- موضعی است هرگاه j(r)^2=. .همچنین برای یک حلقه تعویض پذیر r فرض کنیم c یک عنصر ناصفر از (z( r باشد با این خاصیت که cz( r)=0 گوییم حلقه موضعی r یک حلقه c - موضعی است هرگاه و{0 و z(r)^2={cو z(r)^3=0, نیز xz( r)=0 نتیجه دهد که x عضو {c,0 } است. در این پایان نامه ساخ...
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ژورنال
عنوان ژورنال: International Journal of Molecular Sciences
سال: 2020
ISSN: 1422-0067
DOI: 10.3390/ijms21197002