Synthesis of promiscuous ALK2 inhibitors

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 …

Shorter procedure to access Thieno[2,3-d]pyrimidines

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 …

Last set of DRAK2 inhibitors to be synthesized?

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 …

Are kinase DRAK2 inhibitors active against kinase AURKB in cells? Good news: NO!

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 …

First set of selected compounds against DRAK2 kinase

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 …

Synthesis of a selective inhibitor for DRAK2 kinase

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 …

Chemical probes for understudied kinases

One of the ongoing projects at SGC-UNC is the development of chemical probes for understudied kinases (e.g. MST1-4, TAOK1-3, DCAMKL1, MAP3K2 and MAP3K3). A chemical probe is defined as a small molecule that selectively and potently modulates a protein’s function. Generating chemical probes for understudied kinases is important so we can further understand the biology Read More …