Recent Updates on the Development of Deuterium-Containing Drugs for the Treatment of Cancer

Abstract

Cancer is one of the deadliest diseases in the world. In 2020, 19.3 million cancer cases and 10 million deaths were reported in the world. It is supposed that the prevalence of cancer cases will rise to 28.4 million by 2040. Chemotherapy-based regimens have a narrow therapeutic index, severe adverse drug reactions, and lack metabolic stability. Besides, the metabolism of anticancer produces several non-active and toxic metabolites that reduce exposure of the target site to the parent drug. Therefore, developing better-tolerated and effective new anticancer drugs and modification of the existing anticancer drugs to minimize toxicity and increase efficacy has become a very urgent need. Deuterium incorporation reduces the metabolism of certain drugs that are breakdown by pathways involving hydrogen-carbon bond scission. For example, CYP450 mediated oxidative metabolism of drugs that involves the breakdown of a hydrogen-carbon bond affected by deuteration. Deuterium incorporation into the drug increases the half-life and reduces the dose, which provides better safety and efficacy. Deutetrabenazine is the first deuterated form of tetrabenazine approved to treat chorea associated with Huntington’s disease and tardive dyskinesia. The study revealed that Deutetrabenazine has fewer neuropsychiatric side effects with favorable safety than tetrabenazine. The current review highlights the deuterium kinetic isotope effect on drug metabolism, deuterated compound pharmacokinetic property, and safety profile. Besides, this review explains the deuterated anticancer drug development update status.

Sulfonium Salt Reagents for the Introduction of Deuterated Alkyl Groups in Drug Discovery

“…The pharmacokinetics and predicted metabolic sites of drug candidates, deuterated at the α‐position to heteroatoms, have been widely investigated [3,10,19] . Straightforward methods based on the transition‐metal‐catalyzed H/D exchange reaction (deuteration) at the α‐position to heteroatoms can be a powerful tools for directly incorporating deuterium atoms into drugs [1,20–27] .…”

“…[3,10,18] The pharmacokinetics and predicted metabolic sites of drug candidates, deuterated at the α-position to heteroatoms, have been widely investigated. [3,10,19] Straightforward methods based on the transition-metal-catalyzed H/D exchange reaction (deuteration) at the α-position to heteroatoms can be a powerful tools for directly incorporating deuterium atoms into drugs. [1,[20][21][22][23][24][25][26][27] For example, ruthenium nanocatalysts were used in the direct deuteration of chiral amine substrates, [24,25] and iridium-catalyzed α-deuteration of amine derivatives was also developed.…”

Three Members of Transmembrane-4-Superfamily, TM4SF1, TM4SF4, and TM4SF5, as Emerging Anticancer Molecular Targets against Cancer Phenotypes and Chemoresistance

“…Cancer is one of the most lethal diseases worldwide, as more than 19 million cases and 10 million deaths were reported in 2020, and the number is projected to rise dramatically by 2040 [ 10 ]. Two-thirds of cancer patients die within several years due to tumor recurrence and metastasis [ 11 ].…”

A near-infrared and lysosome-targeted BODIPY photosensitizer for photodynamic and photothermal synergistic therapy

“…Cancer is becoming one of the most threatening diseases to human health. 1 Traditional treatment methods, such as radiotherapy and chemotherapy, are widely used and improve survival rates for malignant tumor patients. Still, these methods also cause serious side effects on healthy organ function.…”