Within druggable target space, new small-molecule modalities, particularly covalent
inhibitors and targeted degraders, have expanded the repertoire of medicinal chemists …

Transcriptional deregulation has emerged as a hallmark of several cancer types. In
metastatic castration-resistant prostate cancer, a stage in which systemic androgen …

Selective degradation of the cyclin-dependent kinases 12 and 13 (CDK12/13) presents a
novel therapeutic opportunity for triple-negative breast cancer (TNBC), but there is still a lack …

Covalent protein kinase inhibitors exploit currently noncatalytic cysteines in the adenosine
5′-triphosphate (ATP)-binding site via electrophiles directly appended to a reversible …

Cell cycle-dependent protein kinase 12 (CDK12) plays a key role in a variety of
carcinogenesis processes and represents a promising therapeutic target for cancer …

Selective degradation of cyclin-dependent kinases 12 and 13 (CDK12/13) emerges as a
new potential therapeutic approach for triple-negative breast cancer (TNBC) and other …

Highlights•A series of dual-target inhibitors of CDK12-PARP1 were designed and
synthesized.•The SARs of dual-target inhibitors of CDK12-PARP1 were investigated.•The …

The cyclin-dependent kinase CDK12 has garnered interest as a cancer therapeutic target as
DNA damage response genes are particularly suppressed by loss of CDK12 activity. In this …

In the wake of the development of the concept of cell cycle and its limiting points, cyclin-
dependent kinases (CDKs) are considered to play a central role in regulating cell cycle …

Bone sarcomas are rare heterogeneous tumors that affect patients of all ages including
children, adolescent young adults, and older adults. They include many aggressive …