Introduction: Acetyl-CoA Carboxylase (ACC) is an essential rate-limiting enzyme in fatty acid metabolism. For many years, ACC inhibitors have gained great attention for developing therapeutics for various human diseases including microbial infections, metabolic syndrome, obesity, diabetes, and cancer. Areas covered: We present a comprehensive review and update of ACC inhibitors. We look at the current advance of ACC inhibitors in clinical studies and the implications in drug discovery. We searched ScienceDirect (https://www.sciencedirect.com/), ACS (https://pubs.acs.org/), Wiley (https://onlinelibrary.wiley.com/), NCBI (https://www.ncbi.nlm.nih.gov/) and World Health Organization (https://www.who.int/). The keywords used were Acetyl-CoA Carboxylase, lipid, inhibitors and metabolic syndrome. All documents were published before June 2019. Expert opinion: The key regulatory role of ACC in fatty acid synthesis and oxidation pathways makes it an attractive target for various metabolic diseases. In particular, the combination of ACC inhibitors with other drugs is a new strategy for the treatment of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Expanding the clinical indications for ACC inhibitors will be one of the hot directions in the future. It is also worth looking forward to exploring safe and efficient inhibitors that act on the BC domain of ACC.

The JAK2/STAT pathway is hyperactivated in many cancers, and such hyperactivation is associated with a poor clinical prognosis and drug resistance. The mechanism regulating JAK2 activity is complex. Although translocation of JAK2 between nucleus and cytoplasm is an important regulatory mechanism, how JAK2 translocation is regulated and what is the physiological function of this translocation remain largely unknown. Here, we found that protease SENP1 directly interacts with and deSUMOylates JAK2, and the deSUMOylation of JAK2 leads to its accumulation at cytoplasm, where JAK2 is activated. Significantly, this novel SENP1/JAK2 axis is activated in platinum-resistant ovarian cancer in a manner dependent on a transcription factor RUNX2 and activated RUNX2/SENP1/JAK2 is critical for platinum-resistance in ovarian cancer. To explore the application of anti-SENP1/JAK2 for treatment of platinum-resistant ovarian cancer, we found SENP1 deficiency or treatment by SENP1 inhibitor Momordin Ic significantly overcomes platinum-resistance of ovarian cancer. Thus, this study not only identifies a novel mechanism regulating JAK2 activity, but also provides with a potential approach to treat platinum-resistant ovarian cancer by targeting SENP1/JAK2 pathway.

The phosphate group functionalized metal-organic frameworks (MOFs) as the adsorbent for removal of U(VI) from aqueous solution still suffer from low adsorption efficiency, due to the low grafting rate of groups into the skeleton structure. Herein, a novel phosphate group functionalized metal–organic framework nanoparticles (denoted as Fe₃O₄@SiO₂@UiO-66-TPP NPs) designed and prepared by the chelation between Zr and phytic acid, showing fast adsorption rate and outstanding selectivity in aqueous media including 10 coexisting ions. The Fe₃O₄@SiO₂@UiO-66-TPP was properly characterized by TEM, FT-IR, BET, VSM and Zeta potential measurement. The removal performance of Fe₃O₄@SiO₂@UiO-66-TPP for U(VI) was investigated systematically using batch experiments under different conditions, including solution pH, incubation time, temperature and initial U(VI) concentration. The adsorption kinetics, isotherm, selectivity studies revealed that Fe₃O₄@SiO₂@UiO-66-TPP NPs possess fast adsorption rates (approximately 15 min to reach equilibrium), high adsorption capacities (307.8 mg/g) and outstanding selectivity (S_u = 94.4%) towards U(VI), which in terms of performance are much better than most of the other magnetic adsorbents. Furthermore, the adsorbent could be reused for U(VI) removal without obvious loss of adsorption capacity after five consecutive cycles. The research work provides a novel strategy to assemble phosphate group-functionalized MOFs.

Due to increased drug and radiation tolerance, there is an urgent need to develop novel anticancer agents. In our previous study, we performed a series of structural modifications of ursolic acid (UA), a natural product of pentacyclic triterpenes, and found UA232, a derivative with stronger anti-tumor activity. In vitro experiments showed that UA232 inhibited proliferation, induced G₀/G₁ arrest, and promoted apoptosis in human breast cancer and cervical cancer cells. Mechanistic studies revealed that UA232 promoted apoptosis and induced protective autophagy via the protein kinase R-like endoplasmic reticulum kinase/activating transcription factor 4/C/EBP homologous protein-mediated endoplasmic reticulum stress. In addition, we also found that UA232 induced lysosomal biogenesis, increased lysosomal membrane permeability, promoted lysosomal protease release, and led to lysosome-dependent cell death. Furthermore, UA232 suppressed tumor growth in a mouse xenograft model. In conclusion, our study revealed that UA232 exerts multiple pharmacological effects against breast and cervical cancers by simultaneously triggering endoplasmic reticulum stress and lysosomal dysfunction. Thus, UA232 may be a promising drug candidate for cancer treatment.