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Game-changing pan-TEAD inhibitor for solid tumours

Drug Target Review

The system optimised the molecules that were most likely to succeed in terms of potency, metabolic stability, synthetic accessibility, and more. The novel molecules were further ranked based on their ADME and selectivity profiles.

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Metabolism of macrocyclic drugs

Metabolite Tales Blog

Not only this, the reduction in rotatable bonds and consequent reduction in susceptibility to metabolism is an additional benefit [4]. Although in vitro studies showed low metabolic activity, more than 20 metabolites could be identified, resulting from two main routes.

Drugs 52
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Metabolism of de novo designed macrocyclic drugs

Metabolite Tales Blog

Not only this, the reduction in rotatable bonds and consequent reduction in susceptibility to metabolism is an additional benefit [4]. Although in vitro studies showed low metabolic activity, more than 20 metabolites could be identified, resulting from two main routes.

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N-glucuronidation: the human element

Metabolite Tales Blog

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.

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Metabolism of five membered nitrogen containing heterocycles

Metabolite Tales Blog

2013, 41, 508-517 [link] 21 J. 44, 797–814 [link] Take a look at our other blogs The post Metabolism of five membered nitrogen containing heterocycles appeared first on Hypha Discovery. 1994, 22, 659-662 [link] 18a Xenobiotica , 1986, 16, 11-20 [link] 18b Wood and Fibre Science. 2009, 41, 157-167 [link] 19 Molecules.