Active {natural|all-natural|organic} {products|goods|items|merchandise|solutions} are {an important|an essential|a crucial|a vital} {source|supply} of drug discovery {due to|because of|as a result of|on account of|resulting from|as a consequence of} their {unique|distinctive|special|exclusive|exceptional|one of a kind} biocompatibility, novel-structural framework and {extensive|in depth|substantial|comprehensive} pharmacological activities. The target identification of {natural|all-natural|organic} {products|goods|items|merchandise|solutions} {is the|will be the|may be the|would be the|could be the|is definitely the} {key|important|crucial|essential} to {thoroughly|completely} understanding their mechanism of action and guiding their subsequent structure optimization. Lathyrane diterpenoids isolated {from the|in the} seeds of Euphorbia lathyris in our laboratory {have been|happen to be|have already been} proved to possess {good|great|excellent|very good|fantastic|superior} anti-inflammatory activities in lipopolysaccharide (LPS)-induced macrophages, but their precise target and mechanism of action {remain|stay} unclear. Herein, we employed PROTAC {technology|technologies} combined with quantitative proteomic {analysis|evaluation} to {identify|determine|recognize} the {potential|possible|prospective} targets of lathyrane diterpenoids in macrophages. ZCY-PROTAC, synthesized {based on|according to|depending on|determined by} Lathyrol, the core scaffold structure {of the|from the|in the|on the|with the|of your} most active {natural|all-natural|organic} compound (2S,3S,4S,5R,9S,11R,15R)-15-acetoxy-3- cinnamoyloxy-5-hydroxy-14-oxolathyra-6(17),12E-diene, ZCY-001), intensively degraded a target protein MAFF in mouse and human cells. MST, CETSA and DARTS assays confirmed the direct binding of MAFF with Lathyrol or ZCY020, a {natural|all-natural|organic} {product|item|solution} sharing {the same|exactly the same|the identical|precisely the same|the exact same} core scaffold structure. {Further|Additional} mechanism {studies|research} showed that ZCY020 was capable of inhibiting the formation of a MAFF homodimer, {promoting|advertising} MAFF-Nrf2 heterodimerization, and {thus|therefore|hence|as a result} regulating the transcription and expression of downstream protein HO-1, thereby exerting antioxidant, anti-inflammatory activity and {promoting|advertising} protective mitophagy in LPS-induced inflammation in macrophages and acute lung injury in mice. {Together|With each other|Collectively}, our {research|study|analysis|investigation} indicates that MAFF {is a|is really a|is actually a|can be a|is often a|is usually a} {potential|possible|prospective} target of ZCY020 {and other|as well as other|along with other|and also other} lathyrane diterpenoids, and that PROTAC {technology|technologies} {can be|may be|could be|might be|is often|is usually} an {innovative|revolutionary} {approach|method|strategy} {and a|along with a|as well as a|plus a|and also a|in addition to a} {useful|helpful|beneficial|valuable} supplement for target identification of {natural|all-natural|organic} {products|goods|items|merchandise|solutions}. BuyGrubbs 1st 744253-37-0 manufacturer PMID:23381626
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