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Cambridge MedChem Consulting

Another Chemical Probe

Boehringer Ingelheim have made a new addition to opnMe their portal for free chemical probes.

To foster innovation, we openly share selected molecules with the scientific community to unlock their full potential - all for free, no hidden costs.

The latest addition is a potent Chymase inhibitor, Chymase is a chymotrypsin-like serine protease that is stored in a latent form in the secretory granules of mast cells. Upon stimulation, it is released in its active form into the local tissue, contributing to the activation of TGF-ß, matrix metalloproteases and cytokines.

BI-1942 is a highly potent inhibitor of human chymase (IC50 = 0.4 nM) that can be used to test biological hypotheses involving this target in vitro. With BI-1829 we also offer a structurally close analog that is more than 1000 fold less active (IC50 = 850 nM) and can thus be used as negative control for in vitro studies.

BI-1942

Open Molecules Platform

Boehringer Ingelheim has added it's well-characterised non-covalent ATP-competitive inhibitor of glycogen synthase kinase (GSK-3) Bi-5521 to its open molecule platform opnMe.com.

opnMe.com, the new open innovation portal of Boehringer Ingelheim, aims to accelerate research initiatives and enable new disease biology in areas of high unmet medical need by sharing well-characterized, best-in-class, pre-clinical tool compounds.

BI-5521 is a potent and selective ATP-competitive small molecule inhibitor of glycogen synthase kinase 3 (GSK-3), GSK-3β (IC50) 1.1 nM, with demonstrated in vivo activity. Rat pharmacokinetics are available, together with an inactive related compound.

bI5521

Another useful tool for Target Validation.

Chemical Probes

Recently Boehringer Ingelheim have decided to provide access to a number of chemical probes.

Two new probes for BRD9 and BRD7/9 have been added.

I've added them to the Chemical Probes page.

Neuroscience Chemical Probes

We recently heard that Pfizer is leaving the neuroscience therapeutic area, with a resulting loss of around 300 jobs. This is of course bad news for the scientists involved but I hope the work that was undertaken within Pfizer does not disappear. Chemical probes are critical tools in target identification and validation and arguably even more so in neuroscience. I hope that Pfizer consider releasing some of the well characterised molecules as freely accessible chemical probes, especially if they could also offer a similar but inactive molecule as a negative control. Many of the older tool compounds reported in the literature have been shown to have inadequate selectivity which compromises understanding the biology.

There are many important therapeutic targets within neuroscience but our biological understanding is currently inadequate to justify the investment in drug discovery, a selection of well characterised probes may provide the tools to support the necessary basic biological research.

opnMe Chemical probes from Boehringer Ingelheim

One of the key challenges to exploring interesting targets is having access to high quality molecular probes. A number of organisations have go together to support Chemical Probes Portal which provides information and independent reviews of chemical probes.

The Chemical Probes Portal is designed to change the way scientists find and use small-molecule reagents called chemical probes in biomedical research and drug discovery. The Portal is backed by reviews and commentary from recognised chemical probe experts. Our knowledge-dissemination model, focused on providing accessible expert advice, promises to increase research reproducibility, maximise investment outcomes and accelerate the discovery science that informs the next generation of therapeutic

Recently Boehringer Ingelheim have decided to provide access to a number of chemical probes.

To foster innovation, Boehringer Ingelheim (BI) is openly sharing selected molecules with the scientific community to unlock their full potential. There are two types of Boehringer Ingelheim molecules that you can access on this portal: some for ordering, some for collaboration.

These molecules cover a range of interesting molecular targets.

Target ID
Aurora B inhibitor BI 831266
Autotaxin (ATX) inhibitor BI-2545
BCL6 degrader BI-3802
BCL6 inhibitor BI-3812
CCR1 antagonist BI-9667
CCR10 antagonist BI-6901
CDK8 inhibitor BI-1347
FAS inhibitor BI 99179
FLAP antagonist BI 665915
Glucocorticoid Receptor (GR) Agonist BI 653048
Hep. C virus (HCV) NS5B polymerase inhibitor BI 207127 (Deleobuvir)
Hepatitis C virus (HCV) NS3 protease inhibitor BI-1230
Hepatitis C virus (HCV) NS3 protease inhibitor BI-1388
LFA-1 (lymphocyte function-associated antigen-1) antagonist BI-1950
NHE1 inhibitor BI-9627
PLK1 inhibitor BI-2536
sEH inhibitor BI-1935
SYK inhibitor BI 1002494

Looking at the selective Aurora B kinase inhibitor BI 831266, it is clear that BI is making available high quality molecules, they provide the structure, in vitro activity, together with both in vitro and in vivo DMPK data in multiple species. They also suggest a related compound as a negative control in which the N-Me serves to block the critical hinge binding.

BIcompounds

There is also a co-crystal structure and some counter-screening data, together with key references from the literature. Any data generated can be published without approval from BI.

This looks to be a very exciting initiative and it will be interesting to see if other companies follow suit.

They have also created a search engine BI Miner to search multiple data sources simultaneously (PubMed Central, Medline, Patents, Drug labels, Expression Data, NIH Grants, Clinical Trials), this open access.

biminer