Michael A. Schafroth's research while affiliated with The Scripps Research Institute and other places

... Lysine is not involved in the synthesis of toxins, but is diuretic and promotes the elimination of toxins (Rubin et al., 1960). In addition, studies have shown that lysine administration provides renal protection in salt-sensitive hypertension (Rolleman et al., 2008;Rinschen et al., 2022). Thus, the significantly increased abundance of lysine degradation in the gut flora also contributes to worsening subsequent CKD. ...

... These results pointed to a broad acyl chain remodeling outcome associated with TMEM164 deletion that is reminiscent of the reshuffling of acyl chains in diacyl PLs that accompanies the genetic or pharmacological disruption of the C20:4-preferring acyltransferases LPCAT3 or MBOAT7 (refs. [20][21][22]. One difference in the remodeling profile caused by TMEM164 disruption, however, was the very minor increase in C22:4 ePEs (Fig. 1g,h and Supplementary Dataset 1), which contrasted with the more marked elevation in C22:4 PEs found in LPCAT3-null cells 21,22 . ...

... These initial data show that probe labelling can be visualized in intact living cells, which we expect will enable both spatially and temporally resolved activity maps of more selective drug-like compounds in intact tissues in the future. Notably, visualization of covalent drug-target interactions with cellular resolution in intact brain tissue has only recently achieved (Pang et al., 2022) using a number of alkynylated CNS drug analogs that had previously been advanced by classical ABPP approachesamong them a covalent MAOI that operates by a slightly different mechanism from that of PHZ. ...

... Copper-induced nucleophilic 18 F labeling, which was developed by Gouverneur's (Tredwell et al., 2014;Taylor et al., 2017) and Scott's group (Chu and Qing, 2014), is another strategy for radiofluorination of a non-active aromatic ring. There is easy access to the precursor BPE via Miyaura boration (Ishiyama et al., 1995), which would be complementary to SCIDY synthesis (Rong et al., 2021). Because of this, we also systemically evaluated BPE radiolabeling feasibility in our FX2N module. ...

... This justifies why THC (and other molecules with partial or full agonistic activity on CB1, including the weak psychoactive D9-cis-THC enantiomer, recently demonstrated to occur naturally in Hemp-derived nutraceuticals, both phytocannabinoids and non-cannabinoids, with potential effects on the gastrointestinal tract and the brain-gut axis. (Schafroth et al., 2021), should be absent (or at low, non-psychotropic levels) in hemp-derived food products, as a minimum health safety requirement. With antagonistic or negative allosteric activity on CB1 receptors as an outstanding feature, the pharmacology of CBD is very complex (summarized in Table 5) and underlies its broad biological activities, including neuroprotection, analgesia, antiinflammatory and immune-modulating effects, anxiolytic, spasmolytic, anticonvulsant and antipsychotic effects, mood stabilization, and normalization of sleep disorders, just to name a few (Kicman and Toczek, 2020;Mlost et al., 2020;Britch et al., 2021;Franco et al., 2021;Vitale et al., 2021). ...

... This framework might be more clinically relevant, as the assessment of pathological personality traits may be more predictive of interpersonal problems that contribute to the individual seeking treatment (Fowler et al., 2015), and one neurotransmitter system alone is unlikely to explain all the symptoms of BPD or ASPD. In terms of advancing ECS research into personality disorders, Chen et al. (2021) recently developed a PET radiotracer for MAGL mapping. ...

... It shows a good safety profile 17 and can be considered a close analogue of the marketed kinase inhibitor sunitinib (4, Fig. 1a). DCAF11 has only been targeted by chloroacetamide derivatives before, which were considered valuable tool compounds for cellular investigations 18 , and the discovery of degraders incorporating more tempered electrophiles, such as  -unsaturated amides was deemed highly desirable. The drug-like, natural-product inspired arylidene indolinones define a new DCAF11-ligand class with balanced electrophilic reactivity that may enable the wider exploration of this E3-ligase in chemical biology and medicinal chemistry programs. ...

... Several structural scaffolds of CB 2 R PET tracers have recently been developed [51][52][53][54][55] including pyridine derivatives, oxoquinoline derivatives, thiazole derivatives [56,57], oxadiazole derivatives [58], carbazole derivatives [59], imidazole derivative [60], and thiophene derivatives [61,62]. In this study, our newly developed pyridine derivative [ 18 F]RoSMA-18-d6 (Fig. 3b), which exhibited sub-nanomolar affinity and high selectivity towards CB 2 R (Ki: 0.8 nM, CB 2 R/CB 1 R > 12′000) [63], was selected for CB 2 R-targeted neuroinflammation imaging. ...

... platforms vary in the choice of enrichment handle, for example either iodoacetamide alkyne (IAA), iodoacetamide desthiobiotin (IA-DTB) 22,25 , or more tailored labeling reagents, such as hypervalent iodine probes [50][51][52] and heteroaromatic azoline thioethers (HATs) 53 . Isotopic labeling strategies have emerged as another area of considerable innovation for cysteine chemoproteomics. ...

... 13−15 Positron emission tomography (PET), as a non-invasive imaging technique, can support drug discovery and development by providing valuable information on drug−target engagement, accessing target occupancy, and monitoring treatment. 16 Early developed MAGL radioligands are mainly irreversible ones such as [ 11 C]MA-PB-1, 17 [ 11 C]SAR127303, 18 [ 11 C]PF-06809247, 19 and [ 18 F]PF-06795071 20 (Figure 1). However, irreversible PET tracers could hardly provide comprehensive quantification of the drug−target interaction. ...