Advantages of PROTACs in achieving selective degradation of homologous protein families

• Luxi Yang,
• Xinfei Mao,
• Jingyi Zhang,
• Jing Shu,
• Wenhai Huang,
• Xiaowu Dong,
• Yinqiao Chen and
• Mingfei Wu

Beilstein J. Org. Chem. 2026, 22, 628–661, doi:10.3762/bjoc.22.49

• resistance [61]. Although many small-molecule inhibitors have also been developed for CDK9 so far, due to the high homology of the CDK family, inhibitors always tend to target a variety of CDK members, thereby reducing their specificity as therapeutic agents and chemical probes and results in many adverse

• proliferation [125]. Because long-term treatment with imatinib will lead to drug resistance in CML patients, the second generation of TKI was subsequently developed for treatment [129]. Although TKIs targeting BCR-ABL have achieved significant therapeutic effects, CML patients often need to take such drugs for

• : Serum-glucocorticoid-induced protein kinase (SGK) plays a key role in mediating resistance to phosphoinositide 3-kinase (PI3K)/Akt inhibition in breast cancer cells [132]. It has been reported that different ATP competitive inhibitors have similar affinity for all SGK isoforms [133][134]. Due to the

Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs

• Sophie Day-Riley,
• Sona Krajcovicova,
• Aryaman Raj Sokhal,
• Jan L. Venne,
• Paul Brear,
• Marko Hyvönen,
• Benjamin C. Whitehurst,
• Jason S. Carroll and
• David R. Spring

Beilstein J. Org. Chem. 2026, 22, 611–619, doi:10.3762/bjoc.22.47

• . Despite successes with ATP-competitive inhibitors, small-molecule kinase inhibitors can be limited by reversible target engagement, off-target effects, and susceptibility to resistance mechanisms [7]. These challenges have motivated the exploration of alternative therapeutic modalities that move beyond

Regioselective approach to 5-arylsulfonylisoxazoles and their antimicrobial activity

• Artem S. Sazonov,
• Dmitry A. Vasilenko,
• Denis V. Porfiriev,
• Yuri K. Grishin,
• Rimma A. Gazzaeva,
• Alisa P. Chernyshova,
• Maxim A. Kryakvin,
• Anna A. Baranova,
• Vera A. Alferova and
• Elena B. Averina

Beilstein J. Org. Chem. 2026, 22, 592–602, doi:10.3762/bjoc.22.45

• strategies to combat the antibiotic resistance include, in particular, the synthesis of novel antibacterial agents based on isoxazole derivatives [17]. In this regards, the development of efficient and convenient methods for the sulfonyl-containing isoxazoles synthesis has received great attention. The most

Design and synthesis of an erdafitinib-based selective FGFR2 degrader

• Yumeng Jin,
• Shidong Wang,
• Sihan Pan,
• Shuqi Huang,
• Weichen Zhou,
• Xiaohao Huang,
• Lei Zheng and
• Lingfeng Chen

Beilstein J. Org. Chem. 2026, 22, 583–591, doi:10.3762/bjoc.22.44

• growth factor receptor 2 (FGFR2) to overcome the issues of drug resistance and adverse reactions associated with traditional inhibitors in the treatment of FGFR2-driven tumors. Erdafitinib was employed as the targeting ligand, and its aliphatic amine site was conjugated with a CRBN E3 ligase ligand to

• FGFR2-selective inhibitor, is the first highly selective FGFR2 inhibitor. Although substantial advancements have been made in developing FGFR2-targeted therapeutics, the sustained clinical efficacy of these inhibitors in oncology remains constrained by the emergence of acquired resistance mechanisms

• signaling pathway [35][36]. These advances have driven the development of several selective FGFR2 inhibitors, including erdafitinib, infiglatinib, and FGF401 [37][38][39]. However, issues such as acquired drug resistance and on-target toxicity emerging in clinical applications have limited the long-term

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• enhances its therapeutic efficacy but also helps in overcoming resistance mechanisms that limit the effectiveness of other microtubule-targeting agents. Research continues to explore additional applications of 1 in various cancer types, including non-small cell lung cancer, ovarian cancer, and other soft

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• hydrolysis of phytic acid without phytases is extremely difficult because of its hydrolysis resistance, and only a few studies have considered the utilization of phytic acid as a phosphorus source [6]. In recent years, industrial applications of phytic acid have been investigated for its potential

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• dehydrogenase type 1 (11-β-HSD-1), a key enzyme that alleviates insulin resistance by lowering cortisol production. Compound 157 emerged as a promising 11-β-HSD-1 inhibitor candidate. In 2016, researchers from Boehringer Ingelheim Pharmaceuticals and the University of Pennsylvania reported a concise and

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• properties [1]. Among its notable physical attributes is its high corrosion resistance: metallic zirconium is exceptionally stable toward acids and bases at ambient temperature and is less susceptible to corrosion than titanium. Its low toxicity and excellent biocompatibility have historically supported the

Rapid access to the core of malayamycin A by intramolecular dipolar cycloaddition

• Yilin Liu,
• Yuchen Yang,
• Chen Yang,
• Sha-Hua Huang,
• Jian Jin and
• Ran Hong

Beilstein J. Org. Chem. 2025, 21, 2542–2547, doi:10.3762/bjoc.21.196

• biological agents has led to a rapid emergence of resistance, which in turn diminishes the national-wide and even global-wide food security. Moreover, toxins produced by fungi in diseased crops have serious impacts on animal and human health [2]. There remains high demand to develop new antifungal compounds

• action may not be consistent with those of known fungicide classes. This encouraging characteristic indicates its potential to overcome resistance to other fungicides [6][7][8]. Structurally, malayamycin A belongs to a class of modified nucleosides that mimic UDP (uridine 5′-diphosphate)-linked

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• represents a promising approach to overcoming several limitations associated with traditional monovalent therapeutics, including drug resistance, off-target effects, high dosage requirements, and insufficient specificity. This strategy may pave the way for next-generation anticancer therapies more effective

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• proximity to the fluorescent stopper. The reported findings involving dithienylethene-based rotaxanes prove their promising future in materials applications, mainly due to their high photofatigue resistance. Spiropyran While most spiropyran-based rotaxanes have the photoswitchable unit located on the axle

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• sofosbuvir (2). Fluorination at C2 in the nucleoside results in metabolic stability and resistance to hydrolysis as it destabilizes the formation of a C1 oxocarbenium ion [5][6]. Trifluoromethylated γ-butyrolactones also find applications as antiviral agents, for example, lactone 4 which has activity against

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• -designed Pd@S-1 and H-beta zeolite catalytic system, exhibiting high resistance to coking in presence of NH3. Subsequent carboxylation with CO2 and hydrogenation over Rh/C as catalyst led to racemic proline, an important precursor for pharmaceuticals, in quantitative yield. ᴅ-Proline was then obtained in

Solar thermal fuels: azobenzene as a cyclic photon–heat transduction platform

• Jie Yan,
• Shaodong Sun,
• Minghao Wang and
• Si Wu

Beilstein J. Org. Chem. 2025, 21, 2036–2047, doi:10.3762/bjoc.21.159

• [35][36][37][38][39][40][41]. Notably, the utilization of azobenzene-based materials in solar thermal storage applications is gaining considerable attention due to their advantages in low synthesis cost, facile molecular design, exceptional cycling stability, and superior fatigue resistance [6][8

• enables each azobenzene unit to store >200% more energy than isolated molecules, while achieving multi-order-of-magnitude improved storage lifetime and resistance to material degradation during repeated cycling. Feng and co-workers covalently grafted azobenzene groups onto RGO templates (Figure 3b) and

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• forward and backward isomerisation can occur simultaneously. Moreover, some unwanted photochemical side reactions ΦS can occur, as shown in the Equation 4: A is one state of the photoswitch, B the second state, and B’ a generic degradation product. Fatigue resistance measures how many times the

• photoswitch can be switched before it is degraded by side reactions. It is typically reported as cyclability Z50, which “is the number of cycles required to reduce the initial absorbance at a specific wavelength by 50%” [3]. The quantum yield ΦS of these side reactions determines the resistance to fatigue of

• the E-chair isomer [51]. All the compounds show excellent resistance to fatigue. The behaviour of some (hetero)diazocines was also studied in water and solvent mixtures [50][51]. Interestingly, N-acetyl-diazocine possesses overall comparable properties and a longer thermal half-life, and it is also

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• focusing on the tumor microenvironment to develop supramolecular systems that are highly specific and capable of responding to multiple stimuli. These advanced systems aim to target and penetrate tumor cells effectively, mitigate drug resistance caused by tumor cell uptake, and ultimately enhance clinical

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• stainless steel demonstrates corrosion resistance in individual exposures to concentrated nitric acid or sulfuric acid due to passivation layer formation. However, during nitration using both acids simultaneously, progressive HNO3 consumption and water generation may reduce acid concentrations below

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• resistance [1][2][3][4]. In addition to their conventional use, azodyes have unique optical properties, defined by the E/Z isomerization [5][6] and by the tautomeric proton exchange [3][7][8][9][10][11], when a OH or NH group is present on a suitable position in the molecule. Both processes are strongly

N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• Biochemistry, Federal University of Lafia, Nigeria 10.3762/bjoc.21.103 Abstract Pseudomonads strains represent a promising source of bioactive compounds with potential pharmaceutical applications. The necessity to find new drugs is underscored by the increased concern over antimicrobial resistance in the

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• of action and a longer half-life (to improve total cure rates and forestall the development of drug resistance) [2]. Unfortunately, partial artemisinin resistance has been documented in Southeast Asia for more than a decade, and parasites with partial artemisinin resistance have been detected in

• patient isolates in African geographies [1][2]. P. falciparum isolates have also been detected in various global regions with at least some measure of resistance to all frontline ACT partner drugs [1][2]. New chemotherapeutics are urgently needed to manage malarial disease and forestall or circumvent ACT

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• , metallic gold is easily reduced to Au− [2]. Adding to the aforementioned properties, the excellent resistance against corrosion makes gold a vital element for use in a wide range of electronic applications. Some common devices that contain gold include smartphones, in which it is used in the circuit boards

• and/or audio, bringing the benefit of enhanced signal transmission (because of its high conductivity), reliability and durability (a direct result of its high resistance to oxidation) [7][8]. In medicine, gold is used as an inert and non-allergenic alternative metal in devices such as pacemakers [9

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• (3.032 eV) and 5e (2.694 eV) emphasize their strong electron-accepting capabilities, while the high IE of 5c (6.429 eV) indicates its resistance to electron donation. These findings suggest that compounds 5c and 5e are highly reactive and suitable for applications requiring active electron transfer

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• resistance, and maintain ion balance (e.g., LiClO4, n-Bu4NBF4), and active electrolytes, which participate directly in redox reactions, acting as oxidizing or reducing agents (e.g., H2SO4, Et4NOH). Choosing the proper electrolyte affects reaction efficiency, selectivity, and overall performance. Electrodes

• was performed. The use of graphite and RVC gave good results. Nickel, graphite, and platinum electrodes were examined as the cathodes. Results showed that platinum and nickel performed better than graphite in the cathode due to their higher conductivity and lower electrical resistance. When platinum

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• diseases: ADCs have shown remarkable success in treatment of highly refractory diseases. Their ability to overcome resistance makes them valuable options for patients who previously had limited treatment choices. ADCs consist of three main components (Figure 1): (1) Monoclonal antibody (mAb): The antibody

Semisynthetic derivatives of massarilactone D with cytotoxic and nematicidal activities

• Rémy B. Teponno,
• Sara R. Noumeur and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 607–615, doi:10.3762/bjoc.21.48

• ; nematicidal activity; Introduction Cancer continues to be responsible for morbidity and mortality all over the world. Endophytic fungi have been shown to be an important source of secondary metabolites endowed with interesting cytotoxic activities. However, resistance to cancer therapies is a persistent

• challenge in clinical practice. This resistance often leads to treatment failure and poor survival outcomes for patients [1]. Another ongoing problem is the excessive use of chemical pesticides such as methyl bromide, carbamates, and organophosphates to control plant-parasitic nematodes that has shown a

• negative impact on the environment and human health. Prolonged and widespread applications of these substances have also increased the development of nematode resistance to pesticides [2][3][4]. However, advancements in natural products chemistry have shown that chemical modifications of certain natural