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 …
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.
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 a collaboration between SGC-University of North Carolina-Chapel Hill and M4K Pharma, we plan to synthesize 3 different imidazopyridin pyrazines as promiscuous kinase ALK2 inhibitors, compounds 1-3, Scheme 1. The first step will be the synthesis of key intermediate 10, Scheme 2. The proposed synthesis begins with a nucleophilic aromatic substitution on compound 4 to Read More …
Continuing with the line of delivering a chemical probe for DRAK2/STK17B kinase, we decided to revise the procedure to synthesize analogs with a thieno[2,3-d]pyrimidine core, which are intended to be used as negative control in our DRAK2 inhibition study. We shortened the synthesis of these pyrimidines to 2 steps from the starting material 6-bromo-4-chlorothieno[2,3-d]pyrimidine 1 Read More …
This is what is planned to be the last small set of compounds prepared as STK17B/DRAK2 kinase inhibitors. Here, chemical modifications are made in the “top part” of the parent compound AP-39. The goal is to evaluate the role of other functional groups such as imidazole, tetrazole, and sulfonamides (1-3). Other changes include replacement of Read More …
The original compound donated by Pfizer PFE-PKIS 43 (thienopyrimidine scaffold), showed activity against 3 kinases greater than 70% inhibition in the KinomeSCAN at 1 µM (STK17B/DRAK2, AURKB and SRPK2). In the series of compounds recently synthesized as thienopyrimidine derivatives we seek selective and potent inhibitors for STK17B/DRAK2 only. To further identify off-target activity of these Read More …
Another small set of compounds was recently synthesized, the major change in Set2 is the substitution of the sulfur atom by oxygen or nitrogen. The change was made in position 6 of the pyrimidine ring. These compounds along with others from Set1 are currently under screening in the NanoBRET cellular assay (performed by Carrow Wells).
Several compounds derived from thienopyrimidine scaffolds were recently synthesized to be tested as inhibitors of DRAK2/STK17B kinase. Among these, a set of 12 were selected to determine their potency as IC50 values on a DRAK2 cellular assay. These compounds have different functional groups around the phenyl ring and variation in the position of the sulfur Read More …
Towards the SGC goal of creating a kinase chemogenomic set (KCGS) we have been receiving and profiling kinase inhibitors donated by pharmaceutical companies. One such compound is PFE-PKIS 43 (Scheme 1a). We received this compound from Pfizer and it was screened against 403 kinases at DiscoverX. This compound, originally synthesized and published as part of Read More …
