During treatment, 3 patients (5%) developed transient rashes, with no treatment discontinuation required. HS016 exhibits significant efficacy and an acceptable safety profile in biologic-naïve PFCD patients, though the incremental maintenance strategy shows limited efficacy.

Beyond protein degradation, the diverse biological activities of thalidomide are discussed, including modulation of cytokines, angiogenesis, and immune signaling pathways. Collectively, thalidomide exemplifies how mechanistic insight, synthetic innovation and careful risk-benefit evaluation can transform a once-discarded molecule into a cornerstone of contemporary drug design.

P=N/A, N=23900, Completed, Takeda | Not yet recruiting --> Completed

P2, N=120, Active, not recruiting, Johns Hopkins University | Recruiting --> Active, not recruiting

P3, N=49, Active, not recruiting, UCB Biopharma SRL | Trial completion date: Aug 2034 --> Jul 2026 | Trial primary completion date: Sep 2029 --> Apr 2026

While approved pan-FGFR inhibitors provide clinical benefit, their durability is limited by acquired, often polyclonal, on-target resistance mutations affecting key regions of the FGFR2 kinase domain, including the gatekeeper residue (V565), molecular brake residues (N550, E566, K642), and other key variants...Given FGFR2-associated toxicities and the need for subtype selectivity, FGFR4 inhibition was prioritized as a selectivity determinant, while sparing FGFR1 was considered less critical. Guided by structure-based drug design, a reversible aminopyrimidine screening hit was optimized into a novel covalent inhibitor series active against FGFR2 wild-type and clinically relevant resistance mutations. An advanced lead 13 showed favorable potency, ADME properties, and demonstrated proof-of-concept in vivo efficacy in an FGFR2-amplified xenograft model comparable with the standard of care.

P=N/A, N=881, Active, not recruiting, Celltrion | Recruiting --> Active, not recruiting

P2, N=115, Recruiting, Navigator Medicines, Inc.

P2, N=99, Recruiting, Sanofi

Together, our findings indicate that TNF-α blockade by Etanercept exerts neuroprotective and anti-inflammatory actions in the spinal cord of dystrophic mice, providing new insights into the impact of TNF-α signaling on neuroinflammatory processes in DMD.

Current evidence supports a stepwise, phenotype-driven approach in which systemic retinoids remain first-line systemic therapy, while biologics represent a rational and increasingly evidence-supported option for moderate-to-severe, treatment-resistant, or syndromic disease. Further controlled studies are needed to define optimal sequencing, duration, and combination strategies for long-term management.

These compounds incorporated the natural product CGA as the target-binding ligand, conjugated to pomalidomide (an E3 ligase-recruiting moiety) via various synthetic linkers. This study successfully applied an effective strategy for target identification and medication discovery of natural compounds. In addition, CGA-PROTAC A7 was synthesized in one step with an overall yield of 45.96%, providing a feasible route for synthesis and establishing a basis for the combination of natural product polyphenols with PROTAC technology.