Discovery and preclinical evaluations of TQB3616, a novel CDK4-biased inhibitor.

Among small-molecule CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) approved for metastatic breast cancers, abemaciclib has a more tolerable adverse effects in clinic. This is attributable to preferential inhibition of CDK4 over CDK6. In our search for a biased CDK4 inhibitor, we discovered a series of pyrimidine-indazole inhibitors. SAR studies led us to TQB3616 as a preferential CDK4 inhibitor. TQB3616 exhibited improvements in both enzymatic and cellular proliferation inhibitory potency when tested side-by-side with the FDA approved palbociclib and abemaciclib. TQB3616 also possessed favorable PK profile in multiple species. These differentiated properties, together with excellent GLP safety profile warranted TQB3616 moving to clinic. TQB3616 entered into clinical development in 2019 and currently in phase III clinical trials (NCT05375461, NCT05365178).

Strong infiltrative HHC36 antimicrobial peptide/silver nanoparticles-loaded carboxymethyl chitosan/sodium alginate hydrogel for acne vulgaris therapy.

Acne is a common chronic skin inflammatory disease closely related toCutibacterium acnes(C. acnes), which affects the life quality of patients worldwide, especially adolescents and young adults. However, the physical barrier of the skin makes drugs difficult to infiltrate effectively into infected site, causing acne hard to cure and easy to recur. Herein, we developed an antibacterial skin dressing with strong infiltration of antibacterial agents which can co-delivery small-molecular antimicrobial agents through stratum corneum deeply into dermis, achieving high antimicrobial efficacy. The antibacterial dressings were constructed with carboxymethyl chitosan/sodium alginate (CMCS/SA) hydrogel loading with HHC36 (an antimicrobial peptide) and silver nanoparticles (AgNPs) conjugates (Ag-H2/CMCS/SA hydrogel). The released Ag-H2from Ag-H2/CMCS/SA hydrogel can early infiltrate into dermis, co-delivery HHC36 and AgNPs due to the infiltration and targeting of HHC36, presenting the superior antibacterial effect compared to HHC36 or AgNPs alone and killing 100%C. acnesand 100%Staphylococcus epidermidis(S. epidermidis) at a very low concentration of Ag-H2(15µg ml-1A g with 7.1µg ml-1HHC36). Meanwhile, Ag-H2/CMCS/SA hydrogel was biocompatible due to the natural polysaccharides carboxymethyl chitosan and sodium alginate. The HaCaT cells spread well in Ag-H2/CMCS/SA hydrogel. These results indicate that the co-delivery small-molecular antimicrobial agents is a promising strategy and Ag-H2/CMCS/SA hydrogel has a great potential in the therapy of acne.

Raman scattering enhancement of a single ZnO nanorod decorated with Ag nanoparticles: synergies of defects and plasmons: publisher's note.

This publisher's note corrects an error in the funding section in Opt. Lett.43, 2244 (2018)OPLEDP0146-959210.1364/OL.43.002244.

Raman scattering enhancement of a single ZnO nanorod decorated with Ag nanoparticles: synergies of defects and plasmons.

Surface-enhanced Raman scattering (SERS) of a single ZnO nanorod (NR) is demonstrated by coating with Ag nanoparticles (NPs). An enhancement factor of 1.2×103 and 4.4×102 has been obtained for E2 (high) mode (437 cm-1) and A1 (TO) mode (378 cm-1), respectively. Electron paramagnetic resonance measurements reveal an unintentional donor state in ZnO NRs. The enhancement of deep-level emission and micro-absorption mapping of a single ZnO NR further confirms the presence of the donor state. The SERS is believed to result from the charge transfer between ZnO NRs and Ag NPs, which can be enhanced by the empty donor state in ZnO. Finally, single ZnO NRs coated with Ag can be used as good SERS substrates for small molecule detection. This Letter highlights the interaction between point defects and the SERS effect down to a single semiconductor NR.