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Cambridge MedChem Consulting

Macrocycles in Drug Discovery

I've created a new page in the Drug Discovery Resources section describing the use of macrocycles in drug discovery. With the advent of more challenging drug discovery targets such as protein-protein interactions there is renewed interest in molecules that are beyond the "Rule of 5". Macrocycles despite apparently undesirable physicochemical properties (High MWt, polar surface area etc.) can have good cell penetration and oral bioavailability.

cyclosporin

There is also an upcoming meeting on Macrocycles, 3rd RSC BMCS Medicinal Chemistry Symposium on Macrocycles. Monday-Tuesday, 8th-9th October 2018, GlaxoSmithKline, Stevenage, UK. Full details are here http://www.maggichurchouseevents.co.uk/bmcs/Macrocycles-2018.htm. #BMCS_Macrocycles

The objective of this symposium is to promote scientific interaction between scientists with a shared interest in the field of Macrocycles. This area is responsible for a growing number of therapeutic approaches and development candidates, all of which go ‘beyond the rule-of–five’. As a researcher in this field, come along to hear about the latest advances and also to share in some of the secrets of discovering therapeutic agents which go beyond Lipinski’s rules.

Pitfalls to avoid when building a Computational Therapeutics Company

 

Everyday I seem to hear about another tech company moving into healthcare, whilst I'm certain that Artificial Intelligence and Machine Learning has the potential to make a significant impact this advice should be compulsory reading for all involved.

https://a16z.com/2018/04/30/building-therapeutics-startups/

Drug Discovery Resources Updated

I've made a few additions and updated to the Drug Discovery Resources pages. In particular I've updated the covalent inhibitors page and added additional examples to the molecular interactions page. I've also started updating the ADME section and added a page on half-life and how it might be modulated.

repeated

Molecular Interactions page updated

I've updated the molecular interactions page to add more details on halogens.

Halogens are present in around 25% of drugs, calculated using data from Guide to Pharmacology Database and often used as bioisosteric replacements for H, Methyl, OH and NH2.

Bonds to halogen are significantly weaker than hydrogen bonds but there are many examples in the PDB of carbonyls interacting with halogens with bonds to I, and Br predominating. It is perhaps worth noting that halogens have been introduced into ligands to aid X-ray analysis, but they may also influence binding. Based on the observed bond angles the interaction is between the halogen and pi-cloud of the carbonyl rather than the lone pair with a clear clustering of X--O=C-N dihedral angles of 90° associated with interactions that involve primarily the pi-system of the carbonyl.

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.

RSC-BMCS / RSC-CICAG Artificial Intelligence in Chemistry

The lineup for the RSC-BMCS / RSC-CICAG conference on Artificial Intelligence in Chemistry has been announced.

AI-web-image-1

Twitter hashtag - #RSC_AIChem

09.00 Registration, refreshments, and exhibition
10.00 Presentation title to be confirmed Marwin Segler, Benevolent AI, UK
10.30 Presentation title to be confirmed Nadine Schneider, Novartis, Switzerland
11.00 Refreshments, exhibition and posters
11.30 Keynote: What I learned about machine learning - revisited Bob Sheridan, Merck, USA
12.30 Lunch, posters and exhibition
14.00 Molecular de novo design through deep learning Ola Engkvist, AstraZeneca, Sweden
14.30 Scaling de novo design, from single target to disease portfolio Wilhem van Hoorn, Exscientia, UK
15.00 Refreshments, posters and exhibition
15.30 Investigating clusters in solvent data using K-means Ella Gale, University of Bristol, UK
16.00 Deep learning and chemical data Colin Batchelor, Royal Society of Chemistry, UK
16.30 Automation, analytics and AI Darren Green, Molecular Design UK, RD Platform Technology & Science, GlaxoSmithKline, UK
17.00 Drinks reception
18.00 Close

Register here.

Friday, 15th June 2018, Royal Society of Chemistry at Burlington House, London, UK
Poster closing date is 13th April
Bursary closing date is 3rd May

Macrocycles 2018: 3rd RSC BMCS Medicinal Chemistry Symposium on Macrocycles

Take note of the closing dates for abstracts

Applications for oral and poster presentations are welcome. Posters will be displayed throughout the meeting and applicants should indicate whether they wish to be considered for a flash oral presentation when submitting an abstract (two minutes, single slide).The closing dates of 28th February (oral) and 8th August (poster).

PhD Student and Post-Doc Conference Bursaries

Did you know that most BMCS sponsored meetings have a number of bursaries available for PhD and post-doctoral students? Normally up to a value of £250, these awards help to cover registration and travel costs. Preference will be given to members of the RSC (and meeting co-sponsors if applicable), especially those who are selected to give posters.

Macrocycles 2018 meeting #BMCS_Macrocycles

Monday-Tuesday, 8th-9th October 2018, GlaxoSmithKline, Stevenage, UK

Web image-2-sml

The objective of this symposium is to promote scientific interaction between scientists with a shared interest in the field of Macrocycles. This area is responsible for a growing number of therapeutic approaches and development candidates, all of which go ‘beyond the rule-of–five’. As a researcher in this field, come along to hear about the latest advances and also to share in some of the secrets of discovering therapeutic agents which go beyond Lipinski’s rules.

Full details and application forms are here http://www.maggichurchouseevents.co.uk/bmcs/Macrocycles-2018.htm.

Molecular Interactions page updated

I've updated the Molecular Interactions page expanding the section on hydrogen bonds.

The MycetOS (Mycetoma Open Source) project was

The MycetOS (Mycetoma Open Source) project was launched today by the University of Sydney, Erasmus MC, and the Drugs for Neglected Diseases initiative (DNDi) to use an Open Pharma approach to discover compounds that could lead to new treatments for patients suffering from fungal mycetoma (eumycetoma), a devastating disease for which current treatments are ineffective, expensive, and toxic.

More details here….

Join the discussion https://www.reddit.com/r/OpenSourceMycetoma/

or Twitter https://twitter.com/MycetOS

Files here https://github.com/OpenSourceMycetoma

Target Validation page updated

I've just updated the target validation page, highlighting some of the problems with the use of antibodies.