J Enzyme Inhib Med Chem
· 2025 Dec · PMID 40916193
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Sodium-dependent multivitamin transporter (SMVT) is a biotin transporter over-expressed in various types of cancer cells and is commonly studied for targeted drug delivery using biotin conjugates. However, such conjugate...Sodium-dependent multivitamin transporter (SMVT) is a biotin transporter over-expressed in various types of cancer cells and is commonly studied for targeted drug delivery using biotin conjugates. However, such conjugates lack the carboxyl group needed for recognition by SMVT. Previously, we proposed that SMVT is unlikely the transporter of biotin conjugates. To experimentally assess this hypothesis, we examined intracellular enrichment and activation of the biotin-conjugated version of a well-established CO prodrug pair in cell culture. Although prodrug enrichment in SMVT-over-expressing cells was observed, this enrichment was not affected by excess biotin, indicating the lack of competition for SMVT. Additionally, two biotin analogs lacking the carboxyl group exhibited either augmentative or inhibitory effects depending on specific structural features. These findings support the notion that SMVT is not the transporter of biotin conjugates and underscore the need for further mechanistic studies of the transport mechanism(s) of biotin conjugates.
J Enzyme Inhib Med Chem
· 2025 Dec · PMID 40916000
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Current antithrombotic therapies face dual constraints of bleeding complications and monitoring requirements. Although natural hirudin provides targeted thrombin inhibition, its clinical adoption is hindered by sourcing...Current antithrombotic therapies face dual constraints of bleeding complications and monitoring requirements. Although natural hirudin provides targeted thrombin inhibition, its clinical adoption is hindered by sourcing limitations. This study developed a recombinant hirudin variant HMg (rHMg) with enhanced anticoagulant activity through genetic engineering and established cost-effective large-scale production methods. The synthesised gene was expressed in BL21 via a pET vector plasmid, followed by nickel-affinity purification. Systematic evaluations demonstrated rHMg's antithrombin activity of 9573 ATU/mg, dose-dependent prolongation of APTT/PT/TT. It has superior thrombin inhibition with the IC and K values were 2.8 and 0.323 nM respectively compared to FDA approved drug bivalirudin (p < 0.001). The high-yield prokaryotic expression of rHMg with enhanced anticoagulant efficacy provides a novel strategy for developing affordable antithrombotic drugs, showing significant potential for cardiovascular disease management.
Plavša-Puž JJ, Brynda J, Ajduković JJ
… +5 more, Bekić S, Ćelić A, Řezáčová P, Škerlová J, Petri E
J Enzyme Inhib Med Chem
· 2025 Dec · PMID 40905588
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Human aldo-keto reductase 1C3 (AKR1C3) is a steroid modifying enzyme involved in cancer progression. Here, A-ring modified 17α-picolyl and 17()-picolinylidene androstane derivatives are shown to inhibit AKR1C3 activity ....Human aldo-keto reductase 1C3 (AKR1C3) is a steroid modifying enzyme involved in cancer progression. Here, A-ring modified 17α-picolyl and 17()-picolinylidene androstane derivatives are shown to inhibit AKR1C3 activity . None of the androstane derivatives have off-target affinity for the androgen receptor, based on a fluorescence assay in yeast cells. The X-ray structure of AKR1C3 in complex with the strongest inhibitor, a 17α-picolyl androstane with a C3-oxime modification, was determined at 1.7 Å resolution. Based on this crystal structure and molecular docking, inhibition of AKR1C3 by the 17α-picolyl or 17()-picolinylidene derivatives depends on interactions between the C3 modification and the NADP cofactor, while the C17α-picolyl or C17-picolinylidene group anchors the inhibitor to AKR1C3. Because one AKR1C3 inhibitor identified here was also previously reported to inhibit CYP17, it may be possible for future researchers to design dual AKR1C3/CYP17 inhibitors based on a steroid scaffold for potential treatment of advanced prostate cancers.
Shi W, Hu M, Han J
… +6 more, Wang L, Jiang Y, Wu H, Liu W, Xiong B, Wang Y
J Enzyme Inhib Med Chem
· 2025 Dec · PMID 40905579
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A series of pinane-based thiazolidione derivatives were synthesised, and their anti-proliferative effects were investigated by CCK-8 assay. All these compounds exhibited anti-proliferation activity against three glioblas...A series of pinane-based thiazolidione derivatives were synthesised, and their anti-proliferative effects were investigated by CCK-8 assay. All these compounds exhibited anti-proliferation activity against three glioblastoma cell lines (U87, T98G, and U251). Compound exhibited the strongest inhibition effect against all three cell lines. Through cellular thermal shift (CETSA) assay and drug affinity responsive target stability (DARTS) assay, compound was demonstrated to directly interact with the CDK2 protein. Additional analyses revealed that inhibited cell migration and arrested the cell cycle in glioblastoma cells while also induced mitochondrial apoptosis and autophagy. Immunoblotting analysis indicated that induced the up-regulation of Bax, cleaved caspase 3, cleaved PARP-1, P62, and LC3B, and the down-regulation of Bcl-2, caspase 3, and PARP-1. Importantly, also demonstrated efficacy in a 3D cell culture model. Together, these results highlight the potential of as a lead compound for the development of novel therapies for glioblastoma.
Dai W, Dai L, Su T
… +6 more, Lin Q, Lin Z, Ye S, Xu P, Chen H, Zheng X
J Enzyme Inhib Med Chem
· 2025 Dec · PMID 40905571
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A green ultrasound-assisted deep eutectic solvent (UAEDES) method was optimised for extracting flavonoid enzyme inhibitors from . Optimal conditions (choline chloride-1,4-butanediol 1:3 molar ratio, 43% water content, 50...A green ultrasound-assisted deep eutectic solvent (UAEDES) method was optimised for extracting flavonoid enzyme inhibitors from . Optimal conditions (choline chloride-1,4-butanediol 1:3 molar ratio, 43% water content, 50 mL/g liquid-to-solid ratio, 80 °C ultrasound for 48 min) yielded 3.15% total flavonoids, 45.2% higher than 50% ethanol extraction. Scanning electron microscopy confirmed cell wall disruption. The UAE-DES extract showed the strongest enzyme inhibition among all extracts tested (IC 35.872 ± 0.294 µg/mL for -glucosidase, 9.126 ± 0.285 μg/mL for tyrosinase), though the -glucosidase inhibition was much weaker than acarbose, while tyrosinase inhibition was comparable to kojic acid. Six flavonoids were identified via UPLC-Q-Orbitrap HRMS, including scutellarein and corylin. Molecular docking revealed strong binding affinities (≤ -5 kcal/mol), with corylin showing the highest binding to both enzymes through hydrogen bonds and van der Waals interactions. This approach supports sustainable discovery of natural enzyme inhibitors for antidiabetic and skin-whitening applications.
Guo P, Wu C, Wang T
… +11 more, Song Y, Liu X, Wang X, Zhu Y, Song B, Zhu Y, Zhang J, Guo L, Tao R, Yu Z, Song B
J Enzyme Inhib Med Chem
· 2025 Dec · PMID 40891362
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Pyrroline-5-Carboxylate Reductase 1 (PYCR1), a member of the PYCR family, is a key enzyme in the proline biosynthesis pathway. Notably, PYCR1 was originally identified via genetic disease research, linking its mutations...Pyrroline-5-Carboxylate Reductase 1 (PYCR1), a member of the PYCR family, is a key enzyme in the proline biosynthesis pathway. Notably, PYCR1 was originally identified via genetic disease research, linking its mutations to the occurrence of cutis laxa. PYCR1 contributes to the pathogenesis of malignancies and fibrotic diseases via mechanisms involving metabolic reprogramming, Extracellular Matrix (ECM) remodelling, and redox homeostasis maintenance. PYCR1 upregulation has been reported in multiple malignancies including Hepatocellular Carcinoma (HCC), Lung Cancer (LC), Breast Cancer (BC), Bladder Cancer (BlC), and Gastric Cancer (GC), where it has been shown to promote cancer proliferation, migration, and therapy resistance, correlating significantly with advanced cancer stages and poor prognosis. On the other hand, in fibrotic disorders, PYCR1-mediated proline metabolism has been linked to the progression of pulmonary, myocardial, and cutaneous fibroses. Notably, although PYCR1-targeted small-molecule inhibitors have demonstrated therapeutic potential in preclinical studies, their clinical translation is yet to be validated.
J Enzyme Inhib Med Chem
· 2025 Dec · PMID 40891353
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The quest for effective and safe treatments for diabetes mellitus has led to the exploration of natural metabolites as potential α-glucosidase inhibitors. This study delves into the inhibition mechanism of wedelolactone...The quest for effective and safe treatments for diabetes mellitus has led to the exploration of natural metabolites as potential α-glucosidase inhibitors. This study delves into the inhibition mechanism of wedelolactone against α-glucosidase and its hypoglycaemic activity. Activity assay results discovered that wedelolactone functioned as a mixed-type inhibitor, with an IC of 39.12 ± 2.54 μM, surpassing the potency of the standard drug acarbose. Employing multi-spectra methods, our findings indicated that wedelolactone binding induced conformation changes in α-glucosidase to attenuate its enzymatic activity, as evidenced by fluorescence quenching, synchronous fluorescence, 3D fluorescence, CD spectra, and ANS assay. Molecular docking studies provided insights into the specific interactions between wedelolactone and α-glucosidase. Collectively, these results laid the groundwork for the potential application of wedelolactone as a natural therapeutic agent in diabetes management.
Madruga E, Sanchez-Santos C, Valenzuela-Martínez I
… +3 more, Ramírez D, Gil C, Martínez A
J Enzyme Inhib Med Chem
· 2025 Dec · PMID 40879442
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Serum and glucocorticoid-regulated kinase 1 (SGK1) is an underexplored kinase involved in several neurodegenerative diseases. Although SGK1 inhibitors are not available on the market, the absence of side effects in two S...Serum and glucocorticoid-regulated kinase 1 (SGK1) is an underexplored kinase involved in several neurodegenerative diseases. Although SGK1 inhibitors are not available on the market, the absence of side effects in two SGK1 knockout mouse models supports the development of brain-penetrant SGK1 inhibitors to explore their therapeutic potential. Through a combined ligand- and target-based virtual screening using the ECBL, we identified a small heterocyclic molecule with SGK1 inhibitory activity (IC = 0.66 ± 0.25 μM). Molecular dynamics simulations revealed two potential binding modes for the candidate compound, offering valuable insights for the further optimisation of this hit. The compound was predicted to be brain-permeable by both methods and experimental assays. It also demonstrated a neuroprotective profile in a cellular model of Alzheimer's disease (AD) and showed a favourable cardiovascular safety profile. Finally, systems pharmacology analysis identified the FOXO1/FOXO3/CREB1 axis as the principal signalling pathway regulated by SGK1 in the context of AD.
Mira A, Abdel Bar FM, Foudah AI
… +4 more, Aboutaleb MH, Ibrahim TS, Hassan AHE, Khalil AT
J Enzyme Inhib Med Chem
· 2025 Dec · PMID 40856353
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Bio-guided isolation from the Red Sea-derived yielded two new metabolites, 15-deoxy-15-amino-citreohybridonol () and chrysogenotoxin (), alongside five known compounds: emodin (), chrysophanol (), (2-ethylhexyl) phthala...Bio-guided isolation from the Red Sea-derived yielded two new metabolites, 15-deoxy-15-amino-citreohybridonol () and chrysogenotoxin (), alongside five known compounds: emodin (), chrysophanol (), (2-ethylhexyl) phthalate (), haenamindole (), and citreorosein (). Compound exhibited broad-spectrum antibacterial activity against both Gram-positive (MIC: 0.31-0.62 μM; MBC: 0.31-0.62 μM) and Gram-negative bacteria (MIC: 0.15-1.25 μM; MBC: 0.62-2.5 μM). Compound showed potent bactericidal activity against Gram-negative bacteria (MIC: 0.07-0.31 μM; MBC: 0.15-0.62 μM) with MBC/MIC ≤ 4, while compound selectively inhibited (MIC: 0.31 μM; MBC: 0.62 μM). Compounds , , and exhibited low cytotoxicity towards human intestinal epithelial cells (HIEC-6). Molecular docking studies targeting the NDM-1 β-lactamase identified compounds , , and as potential inhibitors of New Delhi metallo-β-lactamase-1 (NDM-1). Molecular dynamics simulations confirmed the structural stability of within the NDM-1 active site. Chrysogenotoxin () was suggested as a promising antibacterial candidate against antibiotic-resistant pathogens.
J Enzyme Inhib Med Chem
· 2025 Dec · PMID 40842071
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Eugenol (4-allyl-2-methoxyphenol), is the major chemical constituent in the essential oil of numerous plant species. Several biological properties have been described for this molecule, including modulation of enzymatic...Eugenol (4-allyl-2-methoxyphenol), is the major chemical constituent in the essential oil of numerous plant species. Several biological properties have been described for this molecule, including modulation of enzymatic targets relevant for the inflammatory response, such as 5-lipoxygenase (5-LOX). As so, there is interest in expanding the chemical space of this molecule to develop new molecules to be used in inflammatory conditions. We describe the chemometric analysis of several eugenol derivatives, which show that the chemical space of the parent molecule was successfully expanded. All molecules were evaluated for their inhibition towards 5-LOX, an important player in inflammatory pathways. Four derivatives exhibited significant 5-LOX inhibitory activity, which prompted further studies. The most promising compounds, 4-allylbenzene-1,2-diol , ethyl-4-(4-allyl-2-methoxyphenoxy)butanoate , 3-(2-methoxy-4-(oxiran-2-ylmethyl)phenoxy)propyl acetate and 4-(3-(-butoxy)-2-hydroxypropyl)-2-methoxyphenol , were submitted to assays to validate their affinity and stability towards 5-LOX, which helped clarify the mechanism by which these molecules interact and inhibit this enzyme.
Wang X, Lu Z, Shao Q
… +12 more, Wang Y, Zhang Z, Wang Z, Jia Q, Zhu J, Song Y, Yuan L, Wang Y, Xu S, He L, Chang J, Gao Y
J Enzyme Inhib Med Chem
· 2025 Dec · PMID 40841277
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Brozopine (BZP), a novel inhibitor of 12/15-lipoxygenase (12/15-LOX), has previously demonstrated efficacy in mitigating inflammatory and oxidative stress-related injury in cerebral ischaemia models. This study aimed to...Brozopine (BZP), a novel inhibitor of 12/15-lipoxygenase (12/15-LOX), has previously demonstrated efficacy in mitigating inflammatory and oxidative stress-related injury in cerebral ischaemia models. This study aimed to evaluate the therapeutic potential and underlying mechanisms of BZP in a mouse model of vascular dementia induced by chronic cerebral hypoperfusion. BZP was administered for 28 days following right unilateral common carotid artery occlusion (rUCCAO) in mice. BZP significantly alleviated cognitive impairment, behavioural deficits, and fine motor function. Mechanistically, BZP inhibited 12/15-LOX, cPLA, p-p38 MAPK/p38 MAPK ratio, tumour necrosis factor-α, interlukin-1β, Aβ deposition, and Tau hyperphosphorylation in the brain and serum of rUCCAO mice. Similar protective effects were observed in both 12/15-LOX-overexpressed and HO-induced HT22 cell models. These findings suggest that BZP exerts its neuroprotective effects by targeting the 12/15-LOX/cPLA/p38 MAPK pathway, offering a promising therapeutic strategy for mitigating the progression of cognitive impairment.
Liu T, Kan CH, Zheng Y
… +7 more, Tsang TF, Liu Y, Tsang MW, Fang H, Lam LY, Yang X, Ma C
J Enzyme Inhib Med Chem
· 2025 Dec · PMID 40823998
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Bacterial RNA polymerase (RNAP) requires the NusG factor to facilitate transcription, with the RNAP clamp-helix domain (CH) serving as the primary binding site for NusG and representing a promising target for antimicrobi...Bacterial RNA polymerase (RNAP) requires the NusG factor to facilitate transcription, with the RNAP clamp-helix domain (CH) serving as the primary binding site for NusG and representing a promising target for antimicrobial intervention. In previous work, we unprecedentedly developed a pharmacophore model based on key clamp-helix residues (R270, R278, R281) at RNAP CH essential for NusG binding, which led to the identification of a hit compound exhibiting modest antimicrobial activity against . In this study, we designed a new class of triaryl inhibitors via scaffold hopping, substituting the linear structure of the hit compound with a benzene ring. Antimicrobial testing showed that several newly synthesised lead compounds achieved the minimum inhibitory concentration of 1 µg/mL against drug-resistant , superior to some marketed antibiotics. The following inhibitory and cell-based assays demonstrated the potential of these triaryl compounds as promising candidates for further development as novel antimicrobial agents.
Xia Y, Chang Y, Guan L
… +6 more, Geng Y, Zhang Q, Shen X, Bu Q, Niu MM, Han G
J Enzyme Inhib Med Chem
· 2025 Dec · PMID 40820676
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Overexpression of PLK1 and NRP1 correlate with enhanced proliferative activity in lung cancer cells, thus the development of dual-target PLK1/NRP1 inhibitors holds great therapeutic promise. In this study, five compounds...Overexpression of PLK1 and NRP1 correlate with enhanced proliferative activity in lung cancer cells, thus the development of dual-target PLK1/NRP1 inhibitors holds great therapeutic promise. In this study, five compounds (PLN 1-5) targeting both PLK1 and NRP1 were identified using a multi-step virtual screening approach. PLN-5 showed nanomolar inhibitory potency against PLK1 (IC = 2.07 ± 0.13 nM) and NRP1 (IC = 5.15 ± 0.24 nM), exceeding the positive controls onvansertib and EG00229 by approximately 9-fold and 124-fold, respectively. Molecular dynamics (MD) simulations revealed that PLN-5 maintained a stable binding to the active sites of PLK1 and NRP1. Importantly, MTT assays showed that PLN-5 had significant antiproliferative activity (IC = 0.27 ± 0.02 μM) against human lung cancer cells, with no significant inhibitory effect on normal lung cells. In conclusion, these results demonstrate the therapeutic potential of PLN-5 as a dual-targeting antitumor agent that warrants further development.
J Enzyme Inhib Med Chem
· 2025 Dec · PMID 40793794
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Poxviruses regulate their replication cycle through host phosphorylation pathways, with dual-specific phosphatase H1(DUSP-H1) playing a key role in immune evasion by dephosphorylating STAT1 and inhibiting interferon(IFN)...Poxviruses regulate their replication cycle through host phosphorylation pathways, with dual-specific phosphatase H1(DUSP-H1) playing a key role in immune evasion by dephosphorylating STAT1 and inhibiting interferon(IFN) responses. Given its high conservation across orthopoxviruses, it represents a promising antiviral target. This study screened a flavonoid library against DUSP-H1 from monkeypox virus (DUSP-H1) using a malachite green-based phosphatase assay, identifying Myricetin, (-)-Gallocatechin, Cupressuflavone, (-)-Epigallocatechin gallate, Baicalein, and Herbacetin as potent DUSP-H1 inhibitors (IC: 7.07-14.05 μM). Docking analysis revealed key hydrogen bonding interactions between 5,7-hydroxyl groups of the hydroxyflavone backbone and Asp79 and Arg116 of DUSP-H1, respectively. Additional interactions with Ser23 via the 3'-hydroxyl group seems to enhance binding and effectively blocking the enzyme's active site. These findings align with previous studies on tyrosine phosphatase inhibitors, supporting flavonoids as broad-spectrum viral phosphatase inhibitors. Further structural and pharmacokinetic studies will aid in developing optimised antiviral therapies against monkeypox, variola, and cowpox viruses.
Jiang C, Yang S, Wang Y
… +3 more, Du L, Niu MM, Zhang D
J Enzyme Inhib Med Chem
· 2025 Dec · PMID 40793788
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Poly (ADP-ribose) polymerase 1 (PARP-1) exhibits high expression levels in colorectal cancer (CRC) patients and participates in multiple DNA damage repair pathways, thereby emerging as an attractive target. Herein, we id...Poly (ADP-ribose) polymerase 1 (PARP-1) exhibits high expression levels in colorectal cancer (CRC) patients and participates in multiple DNA damage repair pathways, thereby emerging as an attractive target. Herein, we identified a series of PARP-1 inhibitors (termed as compounds 1-6) by pharmacophore modelling, virtual screening and biological evaluation. Enzyme inhibition assays demonstrated that compound-5 significantly inhibited PARP-1 activity (IC = 0.07 ± 0.01 nM) and exhibited high selectivity for PARP-1 among 63 different kinases. Molecular dynamic simulations indicated that compound-5 stably bound to the catalytic domain of PARP-1. Cellular assays demonstrated that compound-5 significantly inhibited the proliferation of a panel of human CRC cell lines (HCT116, SNU-1, Caco-2, HT-29). The data suggest that compound-5 may be a highly potent and selective PARP-1 inhibitor for CRC therapy.
Albano A, Emmolo R, De Santis R
… +16 more, Patacchini E, Madia VN, Maloccu S, Ialongo D, Ruggieri G, Arpacioglu M, Scipione L, Saccoliti F, Amatore D, Grilli G, Lista F, Esposito F, Tramontano E, Corona A, Di Santo R, Costi R
J Enzyme Inhib Med Chem
· 2025 Aug · PMID 40793777
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COVID-19 pandemic stimulated tremendous efforts to develop therapeutic strategies targeting SARS-CoV-2, leading to the evaluation of a wide range of potential treatments in clinical trials. However, effective therapeutic...COVID-19 pandemic stimulated tremendous efforts to develop therapeutic strategies targeting SARS-CoV-2, leading to the evaluation of a wide range of potential treatments in clinical trials. However, effective therapeutics remain elusive when the development of new variants and the limits of antiviral drugs is considered. Therefore, the development of antiviral drugs against SARS-CoV-2 is of paramount importance. Among potential drug targets, the SARS-CoV-2 nsp13 is highly attractive thanks to its pivotal role in viral replication. Pursuing our studies on the development of nsp13 inhibitors, in this work we describe the design, synthesis, and biological evaluation of novel inhibitors targeting SARS-CoV-2 nsp13. The newly designed -benzyl indole derivatives were active against both enzymatic activities showing measurable IC under 30 μM concentration, while -alkyl derivatives showed less promising results. Interestingly, the tested compounds blocked viral replication with no cytotoxicity. Docking studies predicted their binding into an allosteric conserved site located in the RecA2 domain.
Kossakowski K, Cherniienko A, Zaprutko L
… +1 more, Pawełczyk A
J Enzyme Inhib Med Chem
· 2025 Dec · PMID 40793752
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FDA-approved kinase inhibitors represent a rapidly growing class of targeted therapies with proven clinical success in oncology. However, their occupancy-driven mode of action is often associated with resistance, off-tar...FDA-approved kinase inhibitors represent a rapidly growing class of targeted therapies with proven clinical success in oncology. However, their occupancy-driven mode of action is often associated with resistance, off-target effects, and incomplete inhibition. Proteolysis-Targeting Chimaeras (PROTACs) offer a compelling alternative by promoting complete degradation of oncogenic kinases, thereby enhancing selectivity and resistance reduction. In this review, we provide a comprehensive overview of the rational design, development, and synthetic approaches for PROTACs incorporating FDA-approved kinase inhibitors. We discuss key aspects influencing degrader efficiency, including kinase selectivity, linker design, E3 ligase recruitment, and synthetic strategies. Additionally, we highlight recent advances, emerging trends, and future directions, such as expanding the repertoire of degradable kinases, optimising linker chemistry, and broadening diversity of E3 ligases. A better understanding of these factors will facilitate the continued evolution of PROTAC technology into effective next-generation therapies for kinase-driven diseases.
Chung CH, Hsu KC, Huang MM
… +3 more, Tu HJ, Pan SL, Chao MW
J Enzyme Inhib Med Chem
· 2025 Dec · PMID 40762406
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Pancreatic cancer is among the most lethal malignancies, with a five-year survival rate of only 6%. For patients with metastatic disease, current treatments extend median survival by merely four months. This study addres...Pancreatic cancer is among the most lethal malignancies, with a five-year survival rate of only 6%. For patients with metastatic disease, current treatments extend median survival by merely four months. This study addresses the urgent need for targeted therapies, as no specific drugs are currently available. Clinical analyses revealed significantly elevated RSK2 expression in pancreatic cancer tissues, associated with shorter survival. We aimed to identify a novel RSK2 inhibitor for metastatic pancreatic cancer. Through structure-based virtual screening, we identified NSYSU-115 as a promising candidate with an IC50 of 45.5 nM. At low concentrations, NSYSU-115 significantly suppressed colony formation, while higher concentrations reduced cell viability and proliferation. It also inhibited phosphorylation of IκBα, a known RSK2 substrate, in a dose- and time-dependent manner. Furthermore, NSYSU-115 impaired cell migration and altered epithelial-mesenchymal transition (EMT) markers. These findings highlight NSYSU-115 as a potent kinase inhibitor with promising therapeutic potential for pancreatic cancer treatment.
J Enzyme Inhib Med Chem
· 2025 Dec · PMID 40762397
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In this study, we have aimed to determine the and effects of 23 frequently used dermatologic drugs on human carbonic anhydrase I (hCA I) and II (hCA II). The inhibitory effects of the drugs on hCA I and hCA II were det...In this study, we have aimed to determine the and effects of 23 frequently used dermatologic drugs on human carbonic anhydrase I (hCA I) and II (hCA II). The inhibitory effects of the drugs on hCA I and hCA II were determined by esterase methods. The most potent inhibitors were isotretinoin for hCA I (Ki= 5.75 µM) and valaciclovir for hCA II (Ki= 5.74 µM). Ketotifen (Ki= 6.98 µM), pantoprazole (Ki= 7.16 µM) and acyclovir (Ki= 7.31 µM) were also potent inhibitors for hCA I. Isotretinoin (Ki= 6.54 µM), brivudine (Ki= 7.44 µM) and fluconazole (Ki= 7.91 µM) were also potent inhibitors for hCA II. Terbinafine hydrochloride was a weak CA inhibitor for both of these isoenzymes (Ki= 20.58 µM for hCA I and 20.32 µM for hCA I). Therefore, the drug, having a weak CA inhibitory activity, may be preferred primarily in patients with a skin disease compared to the other drugs due to important physiological functions of CAs. Molecular docking studies have shown that acitretin and isotretinoin, in particular, will inhibit hCA I at lower concentrations and have higher docking scores. For hCA II, it was shown that Isotretinoin and Ketotifen would inhibit at lower concentrations and have higher placement scores.