Peptide design x Deep learning

You know recurrent neural network (RNN) is universally used in machine learning for natural language, handwriting, speech and also chemistry. Recently there are lots of reports that use RNN against SMILES strings to solve chemoinformatics problems. Today I read a short article published from Prof. Gisbert Schneider’s group. URL is below. https://pubs.acs.org/doi/10.1021/acs.jcim.7b00414 They applied RNNContinue reading “Peptide design x Deep learning”

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Applications of Fluorine atom in Drug discovery

Some years ago, there was good review in drug discovery about the applications of fluorine. The perspective was published by researchers in BMS. There were many informations about fluorine based on their experience and published data. I think this is still useful for Med Chem. It was published in 2015 from ACS. https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.5b00258 And recentlyContinue reading “Applications of Fluorine atom in Drug discovery”

Rational design of GPCR biased Ligand

GPCR is one of druggable target. GPCR activation controls many networks of signaling pathways, which for most receptors are mediated by both G proteins and beta-arrestins. Different signaling pathways give different effects. To avoid side effects from G protein signals, designing beta-arrestins selective ligand is useful strategy for drug discovery. And there are lots ofContinue reading “Rational design of GPCR biased Ligand”

PKPD in R.

You know, to drug development understanding PKPD is important. I’m not DMPK dept. but I think it’s better to know about basic PKPD theory. There are some packages about pkpd analysis in R. And I found cool library developed ronkeiser named “PKPDsim”. http://ronkeizer.github.io/PKPDsim/ This library can integrate shiny, so user can calculate PKPD on theContinue reading “PKPD in R.”

Visualizing the process of lead optimization

Some time we set milestones to management of portfolio, or/and to check the progeress of projects. These data were reported document, power point slides etc, so it’s difficult to grasp situation of LO timely. Researchers at GSK published a solution of visualize LO process. It was impressive for me. Link is here. http://www.ncbi.nlm.nih.gov/pubmed/26262898 They calledContinue reading “Visualizing the process of lead optimization”

Passport for compound.

I was interested in the title. “Compound Passport Service” http://dx.doi.org/10.1016/j.drudis.2015.06.011 AZ made passport for compound to manage compound rights tracking. The system can manage status of compounds, like ownership, permission and structure shared. I really impressed with the concept and system because I think that management of compound(and right) logistics is key factor in DrugContinue reading “Passport for compound.”

How to visualize QSAR model.

I often discuss with other chemist(s) about QSAR. And sometime they told me …”QSAR is useful tool for drug discovery, but I don’t understand it. Because QSAR model (i.e. ML) is hard to understand why the compound is good ?” Hmm, I agree his opinion. SVM, NB, RF etc are very useful but these modelsContinue reading “How to visualize QSAR model.”

mishima.syk#6 etc.

Today I presented at mishima.syk#6 about rdkitjs. I wrote very simple script using rdkitjs and d3js. This script can make scatter plot about fraction of Csp3 and molwt and when user mouse over the circle, rdkitjs return molecule image. Like this. I uploaded the script to github. https://github.com/iwatobipen/mishimasyk/tree/master/mishimasyk6 I hope, participants enjoyed my presentation…. TheContinue reading “mishima.syk#6 etc.”

Think about SAR analysis.

I lost a chance of participation in RDKIT-UGM because ticket was sold out. ;-( I’ll try next year…. SAR analysis is key for drug discovery. MMPA is one of major tool, I like the method. Because MMPA is easy to check effect of substituent in molecule. But sometime, it difficult to understand why the parameterContinue reading “Think about SAR analysis.”

review for kinetics

I found nice review about kinetics of drug binding and residence time. http://www.ncbi.nlm.nih.gov/pubmed/25782745 To improve in vitro, in vivo potency, I some time try to get SKR for designing molecule. If I got correlation only residence time and lipophilicity or molecular weight, the information is not so good. Because too liphophilic or heavy molecule isContinue reading “review for kinetics”

TELG

I read following reviews… http://www.sciencedirect.com/science/article/pii/S0960894X14013845 Many pharmaceutical industry is facing low productivity of NME. It is need to focus on right target for drug discovery to improve the productivity. I think this review is nicely ordered in recent drug discovery process. There are some example about target engagement. Pfizer, many of drug discovery project droppedContinue reading “TELG”

Compound Library in Europe

I read a perspective in DDT today. The title was “The Joint European Compound Library: boosting precompetitive research”. Link is following url. http://www.sciencedirect.com/science/article/pii/S1359644614003419 The Joint European Compound Library (JECL) is a key component of the IMI European Lead Factory (ELF) and brings together over 321 000 high-quality, drug-like and lead-like compounds from the in-house collectionsContinue reading “Compound Library in Europe”

MPO about drug discovery

I have question about MPO multi-parameter optimisation in drug discovery. My opinion is that designed molecule’s biological activity and ADMET profile are not always correlate. So, to design molecules that has good profile, I think it is important to get data about molecules not only biological activity but also phys-chem and ADMET profile even ifContinue reading “MPO about drug discovery”