Drug Target Review

SEPTEMBER 20, 2023

“AI will not replace drug discovery scientists, but drug discovery scientists who use AI will replace those who don’t” – comment during EFMC meeting 2018 Progressing a drug molecule from concept to commercialisation typically takes 10-15 years and has high associated costs of up to $2 billion per launched drug, if all failures are factored in.

Drugs 105

Drugs Metabolic Stability Computational Chemistry Pharmaceuticals 105

Metabolite Tales Blog

APRIL 4, 2023

Deuteration at this position was found to block generation of a less selective primary amide metabolite in vivo and increase metabolic stability. Insights into drug metabolism by cytochromes P450 from modelling studies of CYP2D6-drug interactions. link] [2] Zhang and Tang, 2018. 2018 Sep;8(5):721-732.

Small Molecule 52

Small Molecule FDA Approval FDA Drugs 52

Metabolite Tales Blog

DECEMBER 13, 2023

To curb glucuronidation at that position a gem-dimethyl group was incorporated which not only boosted metabolic stability, but also resulted in increased potency of the final lead compound. Figure 4: Optimisation of an IDO1 inhibitor incorporating installation of a gem-dimethyl group to control glucuronidation of a key hydroxyl group.

Small Molecule 59

Small Molecule Metabolic Stability Treatment Pharmacokinetics 59

Metabolite Tales Blog

MARCH 1, 2023

2018, 26, 965-972 [link] 4a Pharmaceutics, 2022, 14, 1001 [link] 5 Phys. 2018, 61, 5, 2041–205 [link] 9 ACS Chem. 2006 , 34, 145-51 [link] 3 Drug Metab. 1980, 8, 34-38 [link] 4 J. Food Drug Anal. 2000, 2, 195-201 [link] 6 Biochem. 1966 98, 266-277 [link] 7 Metabolites. 2023, 13, 1, 92- [link] 8 J. 2019, 14, 2, 142–16 [link] 10 Chem.

Metabolic Stability 52

Metabolic Stability Pharmacokinetics Drugs Science 52

Metabolite Tales Blog

MAY 12, 2023

This was surprising given that replacement of a phenyl with a pyrimidine and fluorination of aryl or heteroaryl rings are techniques often used to increase metabolic stability. Journal of Medicinal Chemistry 2018 61 (23), 10700-10708, [link] [13] Chemical Aspects of Human and Environmental Overload with Fluorine. Elizabeth A.

Drugs 52

Drugs Small Molecule FDA Approval Metabolic Stability 52

Practical Cheminformatics

AUGUST 3, 2023

I wrote more about the problems with this dataset in a Practical Cheminformatics post in 2018. Initially, I would recommend aqueous solubility, membrane permeability, in vitro metabolic stability, and biochemical assays. I have a few ideas. Focus benchmarking efforts on simple, robust, relevant, clearly defined endpoints.

Drugs 94

Drugs Biochemical Assays Metabolic Stability Screening Hits 94