Targeting the relaxin-3/RXFP3 system: a patent review for the last two decades.

Introduction: The neuropeptide relaxin-3/RXFP3 system belongs to the relaxin/insulin superfamily and is involved in many important physiological processes, such as stress responses, appetite control, and motivation for reward. Although relaxin-3 is the endogenous agonist for RXFP3, it can also bind to and activate RXFP1 and RXFP4. Consequently, research has been focused on the development of RXFP3-specific peptides and small-molecule ligands to validate the relaxin-3/RXFP3 system as a novel drug target.

Synthesis, kinetics and cellular studies of new phenothiazine analogs as potent human-TLK inhibitors.

The alterations in the expression patterns of protein kinases often implicate human cancer initiation and progression. Human tousled-like kinases (TLKs), both TLK1/1B and TLK2, are evolutionary kinases found in cell signaling pathways and are involved in DNA repair, replication, and chromosomal integrity. Several reports have demonstrated the numerous roles of TLK1B in the development and progression of cancer its interactions with different partners, and this direct association has made them viable molecular targets for cancer therapy.

Synthesis and Polymerase Recognition of Threose Nucleic Acid Triphosphates Equipped with Diverse Chemical Functionalities.

Expanding the chemical space of evolvable non-natural genetic polymers (XNAs) to include functional groups that enhance protein target binding affinity offers a promising route to therapeutic aptamers with high biological stability. Here we describe the chemical synthesis and polymerase recognition of 10 chemically diverse functional groups introduced at the C-5 position of α-l-threofuranosyl uridine nucleoside triphosphate (tUTP). We show that the set of tUTP substrates is universally recognized by the laboratory-evolved polymerase Kod-RSGA.

Generation of Phenothiazine with Potent Anti-TLK1 Activity for Prostate Cancer Therapy.

Through kinase assays and docking studies, we report the synthesis and biological evaluation of a phenothiazine analog J54 with potent TLK1 inhibitory activity for prostate cancer (PCa) therapy. Most PCa deaths result from progressive failure in standard androgen deprivation therapy (ADT), leading to metastatic castration-resistant PCa. Treatments that can suppress the conversion to mCRPC have high potential to be rapidly implemented in the clinics.

The Endeavours in RAS Inhibition - the Past, Present, and Future.

KRAS mutations are known to be the most recurrent gain-of-function changes instigated in patients with cancer. The RAS gene family is often mutated in most of the human cancers, and the pursuit of inhibitors that bind to mutant RAS continues as a foremost target. RAS is a small GTPase that controls numerous cellular functions, including cell proliferation, growth, survival, and gene expression.

Design, synthesis and biological evaluation of new Myo-inositol derivatives as potential RAS inhibitors.

Ras is a small family of GTPases that control numerous cellular functions like cell proliferation, growth, survival, gene expression, and is closely engaged in cancer pathogenesis. The ras-targeted methodology entails a holy grail in oncology. Nevertheless, there are no specific molecules reported targeting the same, although it is a known oncogene for more than three decades.