While receptor tyrosine kinase-like orphan receptor 1 (ROR1) is typically expressed at low levels or absent in normal tissues, its expression is notably elevated in various malignant tumors and conditions, including chronic lymphocytic leukemia (CLL), breast cancer, ovarian cancer, melanoma, and lung adenocarcinoma. This distinctive feature positions ROR1 as an attractive target for tumor-specific treatments. Currently, several targeted drugs directed at ROR1 are undergoing clinical development, including monoclonal antibodies, antibody-drug conjugates (ADCs), and chimeric antigen receptor T-cell therapy (CAR-T). Additionally, there are four small molecule inhibitors designed to bind to ROR1, presenting promising avenues for the development of PROTAC degraders targeting ROR1. This review offers updated insights into ROR1's structural and functional characteristics, embryonic development implications, cell survival signaling pathways, and evolutionary targeting strategies, all of which have the potential to advance the treatment of malignant tumors.

Herein, we report a dual photoredox/Rh-catalyzed asymmetric allylic substitution reaction with in situ-generated alkyl radical species. Under mild reaction conditions, a broad range of products are obtained in 48-80% yields with 80-98% ee. Notably, the photocatalyst plays a key role in this method, not only assisting the generation of alkyl radicals from 4-alkyl-1,4-dihydropryidines but also facilitating the reduction of pi-allyl-Rh(III) complexes to pi-allyl-Rh(II) complexes. This strategy provides a method for Rh-catalyzed asymmetric allylic substitution with an alkyl radical species, further expanding the reaction patterns beyond the well-established thermal Rh-catalyzed allylic substitution reactions.

Highly regioselective and diastereoselective cis-arylcyclopropanation (ACP) and trans-vinylcyclopropanation (VCP) of 1-alkenes with gem-dichloroalkanes are described. By employing stable and readily available donor carbene precursors and zinc powder as the additive, the cobalt dichloride complex ((PNN)-P-tBu)CoCl2 of a phosphinobipyridine (PNN) pincer with Bu-t substituents on the phosphorus atom catalyzes mild and efficient cyclopropanation with high functional-group compatibility and wide substrate scope, furnishing high diastereoselectivity in the case of trans-VCP that remains underdeveloped. The synthetic potential was demonstrated by late-stage modification of bioactive molecules. Stoichiometric experiments and cyclic voltammetry experiments provide insights into the reaction mechanism and identify key factors to achieve this reaction; of particular importance is relatively slow reduction of gem-dichloroalkane by a formal Co-I species ((PNN)-P-tBu)CoCl to keep the free alkyl radical at low concentration, as elucidated by the relationship between catalytic activity and reduction potentials of four ((PNN)-P-tBu)Co complexes with various electronic properties.

Aim: To develop a robust drug-delivery system using multi-arm amphiphilic block copolymers for enhanced efficacy in cancer therapy. Materials & methods: Two series of amphiphilic polymer micelles, PEG-b-PCLm and PEG-b-PCLm/TPGS, were synthesized. Doxorubicin (DOX) loading into the micelles was achieved via solvent dialysis. Results: The micelles displayed excellent biocompatibility, narrow size distribution, and uniform morphology. DOX-loaded micelles exhibited enhanced antitumor efficacy and increased drug accumulation at tumor sites compared with free DOX. Additionally, 4A-PEG(47)-b-PCL21/TPGS micelles effectively suppressed drug-resistant MCF-7/ADR cells. Conclusion: This study introduces a novel micelle formulation with exceptional serum stability and efficacy against drug resistance, promising for cancer therapy. It highlights innovative strategies for refining clinical translation and ensuring sustained efficacy and safety in vivo.

Recent advances in transition metal-catalyzed o-carborane B-H activation have led to the rapid development of various methodologies for cage boron functionalization. For catalytic cage B-H acyloxylation, intermolecular oxygenation gave products with different regioselectivities (B(3)-, B(4)-, and B(8,9)-selectivities). Herein, an efficient palladium-catalyzed direct cage B(4)-H oxygenation of o-carboranylacetic acids has been achieved, where the carboxylic group serves as not only a directing group, but also a coupling partner. A wide range of substituted o-carboranylacetic acids have been cyclized via the formation of B(4)-O bond to give the corresponding gamma-lactones in modest to excellent yields. A Pd(IV) intermediate is proposed to be involved in the catalytic cycle. This work offers valuable references for the BH/OH dehydrocoupling reactions under mild conditions to produce carborane-featuring functional molecules.

The targeting of cyclin-dependent kinase 7 (CDK7) has become a highly desirable therapeutic approach in the field of oncology due to its dual role in regulating essential biological processes, encompassing cell cycle progression and transcriptional control. We have previously identified a highly selective thieno[3,2-d]pyrimidine- based CDK7 inhibitor with demonstrated efficacy and safety in animal model. In this study, we sought to optimize the thieno[3,2-d]pyrimidine core to discover a novel series of CDK7 inhibitors with improved potency and pharmacokinetic (PK) properties. Through extensive structure-activity relationship (SAR) studies, compound 20 has emerged as the lead candidate due to its potent inhibitory activity against CDK7 and remarkable efficacy on MDA-MB-453 cells, a representative triple negative breast cancer (TNBC) cell line. Furthermore, 20 has demonstrated favorable oral bioavailability and exhibited highly desirable pharmacokinetic (PK) properties, making it a promising lead candidate for further structural optimization.

To combat the crisis of today's synthetic polymers arising from unsustainable production and disposal, it is essential for the synthetic polymer community to reshape the current polymer industry with sustainable polymers. As an emerging class of sustainable polymers, the development of chemically depolymerizable polymers (CDPs), which can undergo closed-loop depolymerization/repolymerization cycles to reproduce virgin polymers without the loss of properties from recovered monomers, offers an ideal solution to preserve finite natural resources, provides a feasible solution to the end-of-life issue of polymer waste, and thereby establishes a circular materials economy. However, two grand key challenges have been encountered in the establishment of practically useful CDPs: how to balance polymerization and depolymerization ability and how to unify conflicted depolymerizability and physical properties. Accordingly, this critical review article presents our vision for summarizing feasible strategies to overcome the above two significant challenges and the design principles for constructing an ideal CDP by highlighting selected major progress made in this rapidly expanding field.