Binding Sites are 3D
I've always found it interesting that whilst everyone recognises that protein binding sites are three dimensional (and chiral) there is a reluctance to have chiral centres in screening hits. This is despite examples were chiral centres aid affinity, selectivity and solubility. I suspect one of the concerns is the ease of follow up for any hits.
I've been working with Liverpool Chirochem to design a 3D rich, homochiral fragment screening library. The real beauty of this library is that the fragments can be easily expanded using validated chemistry in their parallel synthesis lab.
Once you have built a supply of these homochiral building blocks they can of course be put to many different additional uses, covalent fragments, DEL building blocks, and as building blocks for large virtual libraries. All of which can be supported by their parallel synthesis lab.
Cambridge MedChem Meeting
Registration for the SCI / RSC 22nd Medicinal Chemistry Symposium (better known as The Cambridge MedChem Meeting) 10 September - 13 September 2023 is now open.
As usual there are discounts available for RSC and SCI members, and RSC members need to use a discount code
RSC members should enter the Event discount code EJRFChem221 and select “Guest Member” under the section Member type. Delegates will be contacted for their RSC membership number after successful registration. RSC student members should enter the Event discount code EJRFChem221S and select “Guest Member” under the section Member type. Delegates will be contacted for their RSC membership number after successful registration.
You can register here https://www.soci.org/events/fine-chemicals-group/2023/sci--rsc-22nd-medicinal-chemistry-symposium.
As usual there is an outstanding lineup of international speakers.
As part of the conference, there is also the opportunity to participate in a Medicinal Chemistry Workshop which will take place on the Sunday afternoon.
ChEMBL 32 is released!
The fantastic resource ChEMBL has been updated. ChEMBL 32 contains
- 2,354,965 compounds (of which 2,327,928 have mol files)
- 2,995,433 compound records (non-unique compounds)
- 20,038,828 activities
- 1,536,903 assays
- 15,139 targets
- 86,364 documents
More details are here http://chembl.blogspot.com/2023/03/chembl-32-is-released.html.
Data can be downloaded from the ChEMBL FTP site.
Susceptibility testing in antibacterial drug R&D
This looks like an interesting webinar for all those interested in antibiotics research
Susceptibility testing in antibacterial drug R&D
Presentation 1: Pre-clinical antimicrobial susceptibility testing: considerations and challenges (Dee Shortridge):
- Steps for developing an in vitro susceptibility test for your lead compound
- Studies needed to characterize your compound
- Points to consider if your compound is not typical
Presentation 2: Pitfalls and opportunities of susceptibility testing in clinical trials of new antibiotics (Rafael Cantón):
- The introduction of new antimicrobials needs antimicrobial susceptibility testing to define their profile and the alignment with regulators.
- Susceptibility testing data are also used to define both clinical and PK/PD breakpoints.
- Moreover, they can be used to recognize wild type populations and anticipate emergence or resistance.
This is organised by the Global Antibiotic Research & Development Partnership (GARDP) https://gardp.org.
The Global Antibiotic Research & Development Partnership (GARDP) accelerates the development and access of treatments for drug-resistant infections. Together with private, public and non-profit partners, GARDP works to preserve the power of antibiotics for generations to come.
Updated Drug Discovery Resources
I have updated several pages in the Drug Discovery Resources.
Ester and Amide Bioisosteres https://www.cambridgemedchemconsulting.com/resources/bioisoteres/ester_bioisosteres.html
Cysteine Protease inhibitors https://www.cambridgemedchemconsulting.com/resources/hitidentification/focus/cysteineprotease_inhibitors.html
Covalent Inhibitors https://www.cambridgemedchemconsulting.com/resources/lead_identification/covalent.html.
Annual site review
The Drug Discovery Resources website continues to be very popular with 161,922 page views. The pages were visited by over 76,200 viewers and around 20% of the visitors come back on multiple occasions suggesting they find it useful. The visitors come from 180 different countries with the top countries being
- United States (27%)
- United Kingdom (14%)
- India (10%)
- Germany (4%)
- South Korea (3%)
- China (3%)
One of the popular pages in 2021 was COVID-19 and the Identification of "Drug Candidates" a checklist for those using virtual screening to identify potential hits for COVID-19 targets. This has dropped out of the top pages in 2022.
The other most viewed pages were
- Molecular Interactions
- Distribution and Plasma Protein Binding
- Kinase Inhibitors
- Acid Bioisosteres
- Aromatic Bioisosteres
- Aspartic Acid Proteases
- Solvation and desolvation
- HERG Activity
- Fragment based screening
Looking at the operating systems 54% are Windows users, 20% Mac users, 12% Android, 10% iOS and 2% Linux. The browsers of choice are Chrome and Safari with all other below 10%.
I don't know how comprehensive the analytics software is but there is approximately a 54:46 M:F split for Gender.
Hoping everyone has a safe Christmas break.
As always I won't be sending cards but instead donate the money to the MS Society (https://www.mssociety.org.uk).
Predicting sites of metabolism
I updated the page on predicting metabolism
A database of covalent binders
A recent publication describes CovBinderDB DOI is a fantastic resource mined from the PDB that contains 7375 covalent modifications in which 2189 unique covalent binders target nine types of amino acid residues (Cys, Lys, Ser, Asp, Glu, His, Met, Thr, and Tyr) from 3555 complex structures of 1170 unique protein chains. The database can be accessed here https://yzhang.hpc.nyu.edu/CovBinderInPDB/.
I've added it to the Covalent inhibitors page of the Drug Discovery Resources.
EPSRC Centres for Doctoral Training
Very interesting opportunity https://www.ukri.org/opportunity/epsrc-centres-for-doctoral-training/?. Total fund £324,000,000.s