A growing team of groundbreaking scientists around the world are now sharing their lab notebooks online
Protein STK17A or DRAK1 is a serine/threonine kinase that belongs to the death-associated protein kinase family (DAPK). This family is comprised of five members: DAPK1, DAPK2, DAPK3, DRAK1 and DRAK2, being the last two the least studied. As part of our efforts to find inhibitors for understudied kinases, we recently disclosed a high quality chemical Read More …
As part of SGC-UNC’s scaffold hopping strategy to identify new series of compounds active against CaMKK2, we recently submitted a select number of compounds differing in hinge-binder for CaMKK2 enzyme inhibition assay. The hinge-binders included thienopyridine, furopyridine, quinoline, thienopyrimidines, pyrimidine, N-methyl azaindoles and quinazoline, Figure 1. Others are azaindoles, triazolopyridazine, pyrazolopyridine, imidazopyridine etc. Figure 1: Read More …
The protein kinase N3 (PKN3) represents one of the understudied kinases in the human kinome and therefore one of the kinases SGC-UNC wants to target. As part of the UNC-SOLAR program, a summer program for students, Guillermo Correa Otero was working with me in the lab for 9 weeks. Under the supervision of David Drewry, Read More …
Scaffold hopping is a strategy utilized in medicinal chemistry where the core chemical structure of a promising drug candidate is replaced isosterically, which leads to structurally novel compounds. There are many reasons for undertaking this exercise including; improving potency, changing physiochemical properties such as solubility and clogP, enhance ADME properties and to move into new Read More …
Dear colleagues, I want to share with you all the poster presented this past spring 2019 at The American Chemical Society (ACS) National Meeting in Orlando, FL. This summaries our work on the synthesis of DRAK2 inhibitors.
Access to large amounts of core building blocks is essential in drug discovery programs. It enables rapid synthesis of a series which can then give structure activity relationships (SAR) of the drugs and their target. SAR data allows medicinal chemists to determine the group(s) in a structure evoke a change in activity, whether positive or Read More …
In my last post, I reported a new synthetic route to our quinoline series, Scheme 1. The goal was to overcome prior synthetic challenges and to allow for rapid synthesis of many different analogs over a short period of time. Scheme 1: New synthetic route for generating quinoline analogs I have as a result generated large Read More …
Continuing with our goal to synthesize three compounds as ALK2 inhibitors, let’s refer back to Scheme 2 in the previous post on this topic, compounds 6, 8 and 9 were synthesized in good yields (65-90%), however compound 10 could not be obtained. Different conditions were tested to induce the cyclization of the bromo-pyrazine-2-carboxamide 9 Read More …
In order to develop ligands addressing different possible binding sites of the transcription factor brachyury, fragments co-crystallized with this protein should be developed into ligands by using the program SparkTM (Cresset®). Brachyury (T, TBXT) is an essential regulator of the notochord development. Brachyury is primarily expressed in the embryo but not in the majority of normal Read More …
One goal of the CaMKK2 project is to explore the chemistry and biology of novel hinge binders. Various hinge binders showing CaMKK2 inhibition have been identified in the literature and through testing of compounds synthesized in the SGC. Of note in this search was a recent publication by Price et al. (Bioorg. Med. Chem. Lett., Read More …
