Described herein are therapeutic pH responsive compositions comprising a block copolymer and a therapeutic agent useful for the treatment of cancer.

The present disclosure relates to novel RNAi agents designed to decrease the expression of ANGPTL8 in the liver, where the RNAi agents comprise delivery moieties conjugated to oligonucleotides optionally via a linker. The RNAi agents are useful in the treatment of diseases involving the regulation of ANGPTL8 expression.

Disclosed herein are compounds according to Formula (I) comprising PK/PD modulators for delivery of oligonucleotide-based agents, e.g., double stranded RNAi agents, to certain cell types, such for example skeletal muscle cells, in vivo. The PK/PD modulators disclosed herein, when conjugated to an oligonucleotide-based therapeutic or diagnostic agent, such as an RNAi agent, can enhance the delivery of the composition to the specified cells being targeted to facilitate the inhibition of gene expression in those cells.

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Disclosed herein are improved methods of treating hyperglycemia with a combination of an ultrarapid acting insulin and insulin glargine comprising prandial administration of the ultrarapid insulin, and administration of a first dose of insulin glargine within 6 hours of waking for a day.

A camptothecin drug having a highly stable hydrophilic connecting unit and its conjugate, or its pharmaceutically acceptable salt thereof, including methods for preparation thereof, and its applications in preventing and/or treating cancer. The conjugate can specifically bind to receptors highly expressed in tumor cells. The conjugates have excellent water solubility, stability, and homogeneity, and can be used for preventing and/or treating tumors and/or other diseases.

Disclosed are bispecific compounds (degraders) that target α-synuclein protein for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat neurodegenerative diseases.

Disclosed are bispecific compounds (degraders) that target ITK or a zinc finger (ZnF) protein for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat diseases and disorders characterized or mediated by ITK or ZnF protein activity.

A tetra-aza corand compound of formula (Ia) and compound of formula (Ib) and salts thereof. The tetra-aza corand of formula (Ia) and (Ib) of the present invention relates to novel corand entity having a substantially enclosed volume and a framework structure, the compounds are designed as therapeutic carriers for molecule therapeutics delivery and pharmaceutical compositions thereof.

A bioorthogonal molecule can include a molecule having a structure according the above wherein R.sup.1-R.sup.8 are independently selected from H, a substituted or unsubstituted C.sub.1-C.sub.4 alkyl or alkylene group, COOH, COOR.sup.9, COR.sup.9, CONR.sup.9R.sup.10, CN, CF.sub.3, and SO.sub.2R.sup.9, and where R.sup.9 and R.sup.10 are independently selected from H and a substituted or unsubstituted C.sub.1-C.sub.4 alkyl or alkylene group, with the proviso that one of R.sup.3-R.sup.8 comprises a leaving group, and wherein X is O, S, N, SO, SO.sub.2, SR.sup.+, Se, PO.sub.2.sup.−, or NRR′.sup.+, and where R and R′ are independently selected from H or a substituted or unsubstituted C.sub.1-C.sub.4 alkyl or alkylene group. ##STR00001##

The present invention generally relates to artemisinin/dihydroartemisinin (DHA) derivatives, and their use for therapy, in particular cancer therapy. These tumor-homing artemisinin derivatives (THAD) comprise three moieties: an artemisinin/DHA or a derivative thereof, a heptamethine carbocyanine dye (HMCD) residue, and a linker that conjugates the HMCD dye residue to the artemisinin residue. The THAD include compounds wherein the linker is linked to one or two DHA residue(s) via one or more ether bonds, and wherein the linker is linked to two DHA residues via two bonds independently selected from ester, carbamate and thiocarbamate. The THAD of the invention provide improved growth inhibition of cancer cells. The present invention also relates to improved methods of cancer therapy wherein a THAD is administered to a cancer patient. In embodiments, one or more THAD may be co-administered in a coordinated administration schedule. Advantages of the THAD and their use include, among others, improved dose-response and/or efficacy. The invention also relates to new dyes, their drug conjugates, and processes of making them.