FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3180658823> ?p ?o ?g. }

• W3180658823 endingPage "2997" @default.
• W3180658823 startingPage "2977" @default.
• W3180658823 abstract "SBI-0206965, originally identified as an inhibitor of the autophagy initiator kinase ULK1, has recently been reported as a more potent and selective AMP-activated protein kinase (AMPK) inhibitor relative to the widely used, but promiscuous inhibitor Compound C/Dorsomorphin. Here, we studied the effects of SBI-0206965 on AMPK signalling and metabolic readouts in multiple cell types, including hepatocytes, skeletal muscle cells and adipocytes. We observed SBI-0206965 dose dependently attenuated AMPK activator (991)-stimulated ACC phosphorylation and inhibition of lipogenesis in hepatocytes. SBI-0206965 (≥25 μM) modestly inhibited AMPK signalling in C2C12 myotubes, but also inhibited insulin signalling, insulin-mediated/AMPK-independent glucose uptake, and AICA-riboside uptake. We performed an extended screen of SBI-0206965 against a panel of 140 human protein kinases in vitro, which showed SBI-0206965 inhibits several kinases, including members of AMPK-related kinases (NUAK1, MARK3/4), equally or more potently than AMPK or ULK1. This screen, together with molecular modelling, revealed that most SBI-0206965-sensitive kinases contain a large gatekeeper residue with a preference for methionine at this position. We observed that mutation of the gatekeeper methionine to a smaller side chain amino acid (threonine) rendered AMPK and ULK1 resistant to SBI-0206965 inhibition. These results demonstrate that although SBI-0206965 has utility for delineating AMPK or ULK1 signalling and cellular functions, the compound potently inhibits several other kinases and critical cellular functions such as glucose and nucleoside uptake. Our study demonstrates a role for the gatekeeper residue as a determinant of the inhibitor sensitivity and inhibitor-resistant mutant forms could be exploited as potential controls to probe specific cellular effects of SBI-0206965." @default.
• W3180658823 created "2021-07-19" @default.
• W3180658823 creator A5002571575 @default.
• W3180658823 creator A5004279317 @default.
• W3180658823 creator A5004936479 @default.
• W3180658823 creator A5006463358 @default.
• W3180658823 creator A5012147587 @default.
• W3180658823 creator A5012450463 @default.
• W3180658823 creator A5014431006 @default.
• W3180658823 creator A5029750430 @default.
• W3180658823 creator A5039796961 @default.
• W3180658823 creator A5059284814 @default.
• W3180658823 creator A5075307766 @default.
• W3180658823 creator A5075703021 @default.
• W3180658823 creator A5076732044 @default.
• W3180658823 creator A5079623767 @default.
• W3180658823 creator A5088395356 @default.
• W3180658823 date "2021-08-10" @default.
• W3180658823 modified "2023-10-16" @default.
• W3180658823 title "Investigation of the specificity and mechanism of action of the ULK1/AMPK inhibitor SBI-0206965" @default.
• W3180658823 cites W1864635191 @default.
• W3180658823 cites W1965927487 @default.
• W3180658823 cites W1978763812 @default.
• W3180658823 cites W1985829345 @default.
• W3180658823 cites W1993655397 @default.
• W3180658823 cites W2010763118 @default.
• W3180658823 cites W2015787802 @default.
• W3180658823 cites W2020351518 @default.
• W3180658823 cites W2028553047 @default.
• W3180658823 cites W2029968439 @default.
• W3180658823 cites W2031532881 @default.
• W3180658823 cites W2037918682 @default.
• W3180658823 cites W2046822015 @default.
• W3180658823 cites W2065744630 @default.
• W3180658823 cites W2070910260 @default.
• W3180658823 cites W2080107084 @default.
• W3180658823 cites W2080481362 @default.
• W3180658823 cites W2085567056 @default.
• W3180658823 cites W2091469763 @default.
• W3180658823 cites W2092340120 @default.
• W3180658823 cites W2097261862 @default.
• W3180658823 cites W2097363242 @default.
• W3180658823 cites W2101078720 @default.
• W3180658823 cites W2101715194 @default.
• W3180658823 cites W2110283222 @default.
• W3180658823 cites W2122172227 @default.
• W3180658823 cites W2124536446 @default.
• W3180658823 cites W2125990439 @default.
• W3180658823 cites W2126875959 @default.
• W3180658823 cites W2132629607 @default.
• W3180658823 cites W2135704900 @default.
• W3180658823 cites W2137218119 @default.
• W3180658823 cites W2138226825 @default.
• W3180658823 cites W2138319716 @default.
• W3180658823 cites W2143465418 @default.
• W3180658823 cites W2160615487 @default.
• W3180658823 cites W2169520827 @default.
• W3180658823 cites W2517461269 @default.
• W3180658823 cites W2549946117 @default.
• W3180658823 cites W2590955912 @default.
• W3180658823 cites W2610781292 @default.
• W3180658823 cites W2735200095 @default.
• W3180658823 cites W2755578884 @default.
• W3180658823 cites W2783963614 @default.
• W3180658823 cites W2788724769 @default.
• W3180658823 cites W2801072797 @default.
• W3180658823 cites W2810343827 @default.
• W3180658823 cites W2888330909 @default.
• W3180658823 cites W2902605485 @default.
• W3180658823 cites W2911745815 @default.
• W3180658823 cites W2921646079 @default.
• W3180658823 cites W2938098774 @default.
• W3180658823 cites W2952667566 @default.
• W3180658823 cites W2963446625 @default.
• W3180658823 cites W2968904762 @default.
• W3180658823 cites W2991085222 @default.
• W3180658823 cites W3013716420 @default.
• W3180658823 cites W3091874048 @default.
• W3180658823 cites W3097055298 @default.
• W3180658823 cites W3121271451 @default.
• W3180658823 cites W3121539875 @default.
• W3180658823 cites W3134666894 @default.
• W3180658823 cites W4232094630 @default.
• W3180658823 doi "https://doi.org/10.1042/bcj20210284" @default.
• W3180658823 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8370752" @default.
• W3180658823 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34259310" @default.
• W3180658823 hasPublicationYear "2021" @default.
• W3180658823 type Work @default.
• W3180658823 sameAs 3180658823 @default.
• W3180658823 citedByCount "18" @default.
• W3180658823 countsByYear W31806588232021 @default.
• W3180658823 countsByYear W31806588232022 @default.
• W3180658823 countsByYear W31806588232023 @default.
• W3180658823 crossrefType "journal-article" @default.
• W3180658823 hasAuthorship W3180658823A5002571575 @default.
• W3180658823 hasAuthorship W3180658823A5004279317 @default.
• W3180658823 hasAuthorship W3180658823A5004936479 @default.
• W3180658823 hasAuthorship W3180658823A5006463358 @default.

• next