Account Introduction to antibody-drug conjugates (ADCs), covering structure and mechanism, major payload classes, cleavable and non-cleavable linkers, FDA-approved drugs, and emerging site-specific and bispecific ADCs.
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While STAT3 has long been considered a challenging therapeutic target, it remains an exceptionally attractive one for drug discovery. In this article, we examine the rational design and optimization of SD-2301, a potent VHL-recruiting STAT3 PROTAC degrader developed by Prof. Shaomeng Wang’s group. Discover how linker tuning, E3 ligand and STAT3 ligand optimization yielded a highly selective degrader capable of driving complete, long-lasting in vivo tumor regression with a single intravenous dose.
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The tert-butyl group is a commonly employed lipophilic substituent in drug design, yet its susceptibility to cytochrome P450-mediated oxidative metabolism represents a significant pharmacokinetic liability. This article reviews practical bioisosteric strategies for replacing the tert-butyl group to improve metabolic stability while retaining target binding affinity. Two approaches are discussed in detail: (1) the Cp-CF₃ group, a cyclopropane-based bioisostere that eliminates all sp³ C–H bonds and has been validated across multiple scaffolds, including a finasteride analog with a near-doubled HLM half-life; and (2) selective CH₃-to-CF₃ substitution, exemplified by the lead optimization campaign that transformed a PI3Kα inhibitor into Alpelisib, an approved anticancer agent with markedly improved in vivo clearance and oral bioavailability. Together, these case studies illustrate how rational modification of the tert-butyl group can effectively address metabolic liabilities in small-molecule drug candidates.
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This article explores the rise of the oxetane ring - a tiny four-membered heterocycle that has transitioned from a synthetic avoided zone to an indispensable powerhouse tool for lead optimization.
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In June 2025, Arvinas and Pfizer submitted the NDA for Vepdegestrant (ARV-471) — the world’s first PROTAC drug to reach this milestone. Targeted Protein Degradation (TPD) is no longer just a promising concept; it has officially entered the commercialization phase. This article breaks down the science behind PROTACs, explains the three critical molecular modules (E3 ligase ligand + Linker + Warhead), and reveals how AiFChem’s 200,000+ in-stock building blocks — including CRBN/VHL ligands, quinazoline-2,4-dione warheads, and diverse linker precursors — can dramatically accelerate your PROTAC discovery pipeline. Read on to discover ready-to-use catalog numbers and practical R&D tips for your next degrader program.
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While extracellular checkpoints have transformed oncology, diacylglycerol kinases (DGKα/ζ) represent the next frontier as critical "intracellular brakes." This article traces DGK R&D from its 1980s origins to modern medicinal chemistry breakthroughs by leaders like Incyte and BMS. We examine the optimization of 2-purinone-based inhibitors—using "magic methyls" and scaffold hopping—to develop lead compounds like INCB191358. A central focus is the pivotal challenge of contemporary DGK development: balancing robust T-cell activation with the transient pharmacokinetic exposure necessary to prevent systemic autoimmunity.
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Discover 5 core classes of building blocks in drug discovery, including Boronic Acids, Click Chemistry Reagents, and BCP. AiFChem offers 1.3M+ in-stock compounds to accelerate your R&D.
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Explore the breakthrough discovery and clinical success of daraxonrasib (RMC-6236), a first-in-class, oral RAS(ON) multi-selective inhibitor. This technical deep-dive covers the medicinal chemistry journey from macrocyclic scaffolds to the landmark RASolute 302 Phase 3 results in metastatic PDAC. Learn how the shift from "off-state" targeting to active-state tri-complex inhibition is transforming the treatment landscape for RAS-addicted cancers.
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Explore GLP-1 receptor agonists, their mechanisms, and the chemistry behind weight loss drugs. A practical guide to molecular building blocks for drug discovery.
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