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Abstract Many disease-causing proteins have multiple pathogenic mechanisms, and conventional inhibitors struggle to reliably disrupt more than one. Targeted protein degradation (TPD) can eliminate the protein, and thus all its functions, by directing a cell’s protein turnover machinery towards it. Two established strategies either engage catalytic E3 ligases or drive uptake towards the endolysosomal pathway. Here we describe CYpHER (CatalYtic pH-dependent Endolysosomal delivery with Recycling) technology with potency and durability from a catalytic mechanism that shares the specificity and straightforward modular design of endolysosomal uptake. By bestowing pH-dependent release on the target engager and using the rapid-cycling transferrin receptor as the uptake receptor, CYpHER induces endolysosomal delivery of surface and extracellular targets while re-using drug, potentially yielding increased potency and reduced off-target tissue exposure risks. The TfR-based approach allows targeting to tumors that overexpress this receptor and offers the potential for transport to the CNS. CYpHER function was demonstrated in vitro with EGFR and PD-L1, and in vivo with EGFR in a model of EGFR-driven non-small cell lung cancer.

Many disease-causing proteins have multiple pathogenic mechanisms, and conventional inhibitors struggle to reliably disrupt more than one. Targeted protein degradation (TPD) can eliminate the protein, and thus all its functions, by directing a cell's protein turnover machinery towards it. Two established strategies either engage catalytic E3 ligases or drive uptake towards the endolysosomal pathway. Here we describe CYpHER (CatalYtic pH-dependent Endolysosomal delivery with Recycling) technology with potency and durability from a catalytic mechanism that shares the specificity and straightforward modular design of endolysosomal uptake. By bestowing pH-dependent release on the target engager and using the rapid-cycling transferrin receptor as the uptake receptor, CYpHER induces endolysosomal delivery of surface and extracellular targets while re-using drug, potentially yielding increased potency and reduced off-target tissue exposure risks. The TfR-based approach allows targeting to tumors that overexpress this receptor and offers the potential for transport to the CNS. CYpHER function was demonstrated in vitro with EGFR and PD-L1, and in vivo with EGFR in a model of EGFR-driven non-small cell lung cancer. Targeted protein degradation (TPD) can be employed to eliminate disease-causing proteins. Here, the authors present CYpHER, a TPD tool that uses molecules engineered for intracellular target release with drug recycling via transferrin receptor. CYpHER induces depletion of extracellular targets in vitro and in xenograft tumours. [ABSTRACT FROM AUTHOR]

Recently, graphene-based material as a catalyst has crucially shown a novel strategy in furfural synthesis from biomass resources. In this study, sulfonated graphene oxide (SGO) was studied within five different graphene oxide to sulfanilic acid mass ratios of 1:1.5, 1:2.0, 1:2.5, 1:3.0, and 1:3.5 for facile synthesis of furfural from sugarcane bagasse. The structural investigation of those samples was proceeded through Fourier transform infrared spectroscopy, Raman spectroscopy, and energy-dispersive X-ray spectroscopy. The appropriate sample with the sulfur mass percentage of 3.51 %, corresponding to the ratio of 1:3.5, gives out the highest furfural yield was then, conducted with X-ray diffraction, Scanning electron microscopy, Transmission electron microscopy, and Brunauer-Emmett-Teller for further morphological analysis. The influence of catalyst dose, reaction temperature, and time on the yield of furfural using this catalyst revealed that under reaction conditions of 190 °C for 90 min, reaction in a low dose of 5 wt% of SGO solution gave out the highest conversion of furfural (20.6 %). According to the results, SGO showed high application potential for the synthesis of furfural from sugarcane bagasse. [ABSTRACT FROM AUTHOR]