Acta Pharmaceutica最新文献

{"title":"Lipid-based systems with precipitation inhibitors as formulation approach to improve the drug bioavailability and/or lower its dose: a review.","authors":"Mila Kovačević, Mirjana Gašperlin, Alenka Zvonar Pobirk","doi":"10.2478/acph-2024-0023","DOIUrl":"10.2478/acph-2024-0023","url":null,"abstract":"<p><p>Lipid-based systems, such as self-microemulsifying systems (SMEDDS) are attracting strong attention as a formulation approach to improve the bioavailability of poorly water-soluble drugs. By applying the \"spring and parachute\" strategy in designing supersaturable SMEDDS, it is possible to maintain the drug in the supersaturated state long enough to allow absorption of the complete dose, thus improving the drug's bio-availability. As such an approach allows the incorporation of larger amounts of the drug in equal or even lower volumes of SMEDDS, it also enables the production of smaller final dosage forms as well as decreased gastrointestinal irritation, being of particular importance when formulating dosage forms for children or the elderly. In this review, the technological approaches used to prolong the drug supersaturation are discussed regarding the type and concentration of polymers used in liquid and solid SMEDDS formulation. The addition of hypromellose derivatives, vinyl polymers, polyethylene glycol, polyoxyethylene, or polymetacrylate copolymers proved to be effective in inhibiting drug precipitation. Regarding the available literature, hypromellose has been the most commonly used polymeric precipitation inhibitor, added in a concentration of 5 % (<i>m/m</i>). However, the inhibiting ability is mainly governed not only by the physicochemical properties of the polymer but also by the API, therefore the choice of optimal precipitation inhibitor is recommended to be evaluated on an individual basis.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 2","pages":"201-227"},"PeriodicalIF":2.1,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative effects of pravastatin and rosuvastatin on carbohydrate metabolism in an experimental diabetic rat model.","authors":"Hacer Kayhan Kaya, Berjan Demirtas, Beran Yokus, Dilek Aygün Kesim, Ezel Tasdemir, Abdurrahman Sermet","doi":"10.2478/acph-2024-0001","DOIUrl":"10.2478/acph-2024-0001","url":null,"abstract":"<p><p>Statin treatment may increase the risk of diabetes; there is insufficient data on how statins affect glucose regulation and glycemic control and the effects of statins on liver enzymes related to carbohydrate metabolism have not been fully studied. Therefore, we aimed to compare the effects of the statin derivatives, pravastatin, and rosuvastatin, on carbohydrate metabolism in an experimental diabetic rat model. Female Wistar albino rats were used and diabetes was induced by intraperitoneal injection of streptozotocin. Thereafter, 10 and 20 mg kg^-1 day^-1 doses of both pravastatin and rosuvastatin were administered by oral gavage to the diabetic rats for 8 weeks. At the end of the experiment, body masses, the levels of fasting blood glucose, serum insulin, insulin resistance (HOMA-IR), liver glycogen, and liver enzymes related to carbohydrate metabolism were measured. Both doses of pravastatin significantly in creased the body mass in diabetic rats, however, rosuvastatin, especially at the dose of 20 mg kg^-1 day^-1 reduced the body mass signi ficantly. Pravastatin, especially at a dose of 20 mg kg^-1 day^-1, caused significant increases in liver glycogen synthase and glucose 6-phosphate dehydrogenase levels but significant decreases in the levels of glycogen phosphorylase, lactate dehydrogenase, and glucose-6-phosphatase. Hence, pravastatin partially ameliorated the adverse changes in liver enzymes caused by diabetes and, especially at the dose of 20 mg kg^-1 day^-1, reduced the fasting blood glucose level and increased the liver glycogen content. However, rosuvastatin, especially at the dose of 20 mg kg^-1 day^-1, significantly reduced the liver glycogen synthase and pyruvate kinase levels, but increased the glycogen phosphorylase level in diabetic rats. Rosuvastatin, 20 mg kg^-1 day^-1 dose, caused significant decreases in the body mass and the liver glycogen content of diabetic rats. It can be concluded that pravastatin, especially at the dose of 20 mg kg^-1 day^-1 is more effective in ameliorating the negative effects of diabetes by modulating carbohydrate metabolism.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 1","pages":"117-130"},"PeriodicalIF":2.8,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel (±)-<i>trans</i>-<i>β</i>-lactam ureas: Synthesis, <i>in silico</i> and <i>in vitro</i> biological profiling.","authors":"Mladenka Jurin, Višnja Stepanić, Krunoslav Bojanić, Denis Vadlja, Darko Kontrec, Tonko Dražić, Marin Roje","doi":"10.2478/acph-2024-0008","DOIUrl":"10.2478/acph-2024-0008","url":null,"abstract":"<p><p>A diastereomeric mixture of racemic 3-phthalimido-<i>b</i>-lactam <b>2a</b>/<b>2b</b> was synthesized by the Staudinger reaction of carboxylic acid activated with 2-chloro-1-methylpyridinium iodide and imine <b>1</b>. The amino group at the C3 position of the <i>b</i>-lactam ring was used for further structural upgrade. <i>trans</i>-<i>b</i>-lactam ureas <b>4a-t</b> were prepared by the condensation reaction of the amino group of <i>b</i>-lactam ring with various aromatic and aliphatic isocyanates. Antimicrobial activity of compounds <b>4a-t</b> was evaluated <i>in vitro</i> and neither antibacterial nor antifungal activity were observed. Several of the newly synthesized <i>trans</i>-<i>b</i>-lactam ureas <b>4a-c</b>, <b>4f</b>, <b>4h</b>, <b>4n</b>, <b>4o</b>, <b>4p</b>, and <b>4s</b> were evaluated for <i>in vitro</i> antiproliferative activity against liver hepatocellular carcinoma (HepG2), ovarian carcinoma (A2780), breast adenocarcinoma (MCF7) and untransformed human fibroblasts (HFF1). The <i>b</i>-lactam urea <b>4o</b> showed the most potent antiproliferative activity against the ovarian carcinoma (A2780) cell line. Compounds <b>4o</b> and <b>4p</b> exhibited strong cytotoxic effects against human non-tumor cell line HFF1. The <i>b</i>-lactam ureas <b>4a-t</b> were estimated to be soluble and membrane permeable, moderately lipophilic molecules (log<i>P</i> 4.6) with a predisposition to be CYP3A4 and P-glycoprotein substrates. The tools PASS and SwissTargetPrediction could not predict biological targets for compounds <b>4a-t</b> with high probability, pointing to the novelty of their structure. Considering low toxicity risk, molecules <b>4a</b> and <b>4f</b> can be selected as the most promising candidates for further structure modifications.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 1","pages":"37-59"},"PeriodicalIF":2.8,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medicarpin suppresses lung cancer cell growth <i>in vitro</i> and <i>in vivo</i> by inducing cell apoptosis.","authors":"Zongyi Shen, Liqi Yin, Manxia Chang, Haifeng Wang, Mingxuan Hao, Youfeng Liang, Rui Guo, Ying Bi, Jiansong Wang, Changyuan Yu, Jinmei Li, Qiongli Zhai, Runfen Cheng, Jinku Zhang, Jirui Sun, Zhao Yang","doi":"10.2478/acph-2024-0006","DOIUrl":"10.2478/acph-2024-0006","url":null,"abstract":"<p><p>Lung cancer (LC) is the leading cause of cancer deaths worldwide. Surgery, chemoradiotherapy, targeted therapy, and immunotherapy are considered dominant treatment strategies for LC in the clinic. However, drug resistance and meta-stasis are two major challenges in cancer therapies. Medicarpin (MED) is an isoflavone compound isolated from alfalfa, which is usually used in traditional medicine. This study was de sig ned to evaluate the anti-LC effect and reveal the underlying mechanisms of MED <i>in vivo</i> and <i>in vitro</i>. We found that MED could significantly inhibit proliferation, induce apoptosis, and cell cycle arrest of A549 and H157 cell lines. Basically, MED induced cell apoptosis of LC cells by upregu lating the expression of pro-apoptotic proteins BAX and Bak1, leading to the cleavage of caspase-3 (Casp3). Moreover, MED inhibited the proliferation of LC cells <i>via</i> downregulating the expression of proliferative protein Bid. Overall, MED inhibited LC cell growth <i>in vitro</i> and <i>in vivo via</i> suppressing cell proliferation and inducing cell apoptosis, suggesting the therapeutic potential of MED in treating LC.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 1","pages":"149-164"},"PeriodicalIF":2.8,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deguelin inhibits the proliferation of human multiple myeloma cells by inducing apoptosis and G2/M cell cycle arrest: Involvement of Akt and p38 MAPK signalling pathway.","authors":"Kening Sun, Ping Chen, Liang Zhang, Zhidong Lu, Qunhua Jin","doi":"10.2478/acph-2024-0003","DOIUrl":"10.2478/acph-2024-0003","url":null,"abstract":"<p><p>Deguelin exhibits antiproliferative activity against various cancer cell types. Previous studies have reported that deguelin exhibits pro-apoptotic activity against human cancer cells. The current study aimed at further elaborating the anticancer effects of deguelin against multiple myeloma cells. Cell growth estimations were made through MTT assay. Phase contrast microscopy was used for the analysis of the viability of multiple myeloma cells. Colony formation from multiple myeloma cells was studied using a clonogenic assay. Antioxidative assays for determining levels of glutathione (GSH) and superoxide dismutase (SOD) were carried out after treating multiple myeloma cells with deguelin. The apoptosis of multiple myeloma cells was studied using AO/EB and Annexin V-FITC/PI staining methods. Multiple myeloma cell cycle analysis was performed through flow cytometry. mRNA expression levels were depicted using qRT-PCR. Migration and invasion of multiple myeloma cells were determined with the wound-healing and transwell assays, respectively. Deguelin specifically inhibited the multiple myeloma cell growth while the normal plasma cells were minimally affected. Multiple myeloma cells when treated with deguelin exhibited remarkably lower viability and colony-forming ability. Multiple myeloma cells treated with deguelin produced more SOD and had higher GSH levels. The multiple myeloma cell growth, migration, and invasion were significantly declined by <i>in vitro</i> administration of deguelin. In conclusion, deguelin treatment, when applied <i>in vitro,</i> induced apoptotic cell death and resulted in mitotic cessation at the G2/M phase through modulation of cell cycle regulatory mRNAs in multiple myeloma cells.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 1","pages":"101-115"},"PeriodicalIF":2.8,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long non-coding RNA <i>TINCR</i> suppresses growth and epithelial-mesenchymal transition by inhibiting Wnt/<i>β</i>-catenin signaling pathway in human pancreatic cancer PANC-1 cells: Insights from <i>in vitro</i> and <i>in vivo</i> studies.","authors":"Yuan Wei, Ping Zhu","doi":"10.2478/acph-2024-0009","DOIUrl":"10.2478/acph-2024-0009","url":null,"abstract":"<p><p>There is increasing evidence that long non-coding RNAs (lncRNAs) play a crucial role in the development and progression of malignant tumors, particularly pancreatic cancer. In this study, the influence of the lncRNA <i>TINCR</i> on the behavior of human pancreatic cancer cells was investigated with the aim of deciphering its role in growth, migration, and invasion. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to investigate <i>TINCR</i> expression in pancreatic cancer cells. Ectopic expression of <i>TINCR</i> in PANC-1 cells was induced to evaluate the effects on cell viability and apoptosis, examining the apoptotic genes Bax and Bcl-2. Migration and invasion assays were used to measure the impact of <i>TINCR</i> on these cellular processes. <i>In vivo</i> studies using a xenograft mouse model examined the effects of <i>TINCR</i> on tumor growth, epithelial-to-mesenchymal transition (EMT) markers, and the Wnt/β-catenin signaling pathway. PANC-1 cells showed strikingly low <i>TINCR</i> expression compared to other pancreatic cancer cell lines. Ectopic <i>TINCR</i> expression reduced the viability of PANC-1 cells primarily by inducing apoptosis, as evidenced by increased Bax and decreased Bcl-2 expression. Overexpression of <i>TINCR</i> significantly increased the percentage of apoptotic cells. It also decreased the migration and invasion ability of PANC-1 cells, as demonstrated in wound healing and transwell assays. In addition, overexpression of <i>TINCR</i>-suppressed proteins is associated with the Wnt/β-catenin signaling pathway in PANC-1 cells. In the xenograft mouse model, overexpression of <i>TINCR</i> inhibited tumor growth, EMT markers, and proteins associated with the Wnt/β-catenin pathway. This study sheds light on the tumour-suppressive role of <i>TINCR</i> in PANC-1 cells and suggests its potential as a therapeutic target. These results shed light on the molecular mechanisms underlying the impact of <i>TINCR</i> on pancreatic cancer and offer promising opportunities for innovative therapeutic strategies to improve outcomes in this serious malignancy.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 1","pages":"131-147"},"PeriodicalIF":2.8,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical composition and potential antioxidant, anti-inflammatory, and analgesic efficacy of <i>Cistus albidus</i> L.","authors":"Aziz Zouhri, Toufik Bouddine, Naoual El Menyiy, Yahya El-Mernissi, Hassan Laaroussi, Mohamed Chebaibi, Hassan Amhamdi, Abdelhay Elharrak, Hiba-Allah Nafidi, Baye Sitotaw, Yousef A Bin Jardan, Mohammed Bourhia, Lhoussain Hajji","doi":"10.2478/acph-2024-0002","DOIUrl":"10.2478/acph-2024-0002","url":null,"abstract":"<p><p>This study aims to assess the chemical composition of the aqueous extract of <i>Cistus albidus</i> L. leaves, as well as the potential of aqueous and hydroethanol extracts of the leaves and seeds as analgesic, anti--inflammatory, and antioxidant agents. The contents of phenolics and inorganic constituents were determined in <i>C. albidus</i> seeds and leaves; antioxidant capacity was assessed by 3 complementary and diverse tests. The carrageenan-induced paw edema technique was used to investigate the anti-inflammatory effect <i>in vivo</i>, and albumin denaturation to evaluate the anti-inflammatory effect <i>in vitro</i>. The acetic acid-induced contortion test, the tail-flick test, and the plantar test were used to assess the analgesic effi cacy <i>in vivo</i>. Chemical analysis was performed by UPLC-MS/MS to quantify several phenolic compounds including catechin (1,627.6 mg kg^-1), quercitrin (1,235.8 mg kg-1) and gallic acid (628. 2 mg kg^-1). The ICP analysis revealed that potassium and calcium were the main inorganic components in the seeds and leaves of <i>C. albidus</i>. The hydroethanolic extract of the leaves showed the highest content of polyphenols/flavonoids, whereas the highest value of proantho cyanidins was detected in the aqueous extract of the seeds. All extracts showed potent antioxidant activity related to different phenolic compounds (quercetin, gallic acid, astragalin, catechin, and rutin). The aqueous extract of the leaves strongly inhibited paw edema (76.1 %) after 6 h of treatment and showed maximal inhibition of protein denaturation (191.0 µg mL^-1 for 50 % inhibition) and analgesic activity in different nociceptive models. The presented data reveal that <i>C. albidus</i> extracts potentially show antioxidant, anti-inflammatory, and analgesic activities that could confirm the traditional use of this plant.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 1","pages":"81-99"},"PeriodicalIF":2.8,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Furanocoumarin compounds isolated from <i>Dorstenia foetida</i> potentiate irinotecan anticancer activity against colorectal cancer cells.","authors":"Supusson Pengnam, Watcharapa Jitkaroon, Roongtiwa Srisuphan, Pawaris Wongprayoon, Kanok-On Rayanil, Purin Charoensuksai","doi":"10.2478/acph-2024-0004","DOIUrl":"10.2478/acph-2024-0004","url":null,"abstract":"<p><p>Although the anticancer activity of <i>Dorstenia foetida</i> was already observed, the chemical entity responsible for this activity remained unidentified. In this study, the cytotoxic activity of two furanocoumarin compounds, <i>i</i>.<i>e</i>., 5-methoxy--3-(3-methyl-2,3-dihydroxybutyl)-psoralen (<b>1</b>) and 5-methoxy-3-(3-methyl-2,3-dihydroxybutyl)-psoralen diacetate (<b>2</b>) isolated from ethyl acetate fraction of <i>D. foetida</i> (whole plant) was investigated in several cancer cell lines including HN22, MDA-MB-231, HCT116, and HT29. The results revealed that compound <b>2</b> exhibited cytotoxic activity, particularly against colorectal cancer cell lines HCT116 and HT29. The interplay between compound <b>2</b> and irinotecan (Iri) showed synergism against HCT116, which was analyzed by CompuSyn software. The simulation revealed that, at the molar ratio of Iri:<b>2</b> of 1:40, the concentration predicted to achieve a 90 % inhibitory effect when used in the combination would be ~28- and ~4-fold lower than the concentration of compound <b>2</b> and Iri, resp., when used individually. Finally, the percentage of apoptotic cells in the HCT116 line treated with the combination was markedly higher than in the cells treated with the individual agent (60 % apoptotic cells for the combination compared to 17 and 45 % for Iri and compound <b>2</b> monotherapy, resp). In conclusion, our results identified compound <b>2</b> as a plant-derived compound exhibiting anticancer properties that can act synergistically with Iri and warranted further research to assess the potential of this synergism for colorectal cancer treatment.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 1","pages":"67-79"},"PeriodicalIF":2.8,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of mineral composition of leaves and flowers of wild-growing <i>Sambucus nigra</i>.","authors":"Bujar Qazimi, Trajče Stafilov, Katerina Bačeva Andonovska, Krste Tašev, Nikola Geskovski, Shpend Dragusha, Hyrije Koraqi, Valon Ejupi","doi":"10.2478/acph-2024-0007","DOIUrl":"10.2478/acph-2024-0007","url":null,"abstract":"<p><p>The objective of this study was to determine the mineral content in the leaves and flowers of wild-grown <i>Sambucus nigra</i> collected from eleven different locations in Kosovo. The samples were digested in a microwave system using the wet digestion method. The minerals were determined by the application of inductively coupled plasma-atomic emission spectrometry (ICP-AES) and inductively coupled plasma-mass spectrometry (ICP-MS). A total of 31 elements were determined, 15 elements by the ICP-AES method (Al, B, Ba, Ca, Cr, Cu, Fe, K, Mg, Mn, Na, P, Sr, V, and Zn) and 16 elements by the ICP-MS method (Ag, As, Be, Bi, Cd, Co, Cs, Ga, Hg, In, Li, Ni, Pb, Rb, Tl, and U). The leaves of <i>S. nigra</i> show a higher content of minerals compared to the flowers, except for the flower of the sample SN-FL10, which is characterized by a high concentration of Fe, Al, Pb, Be, and Tl. The concentration of heavy metals and toxic elements (Pb, Cd, and Hg) was within the permissible concentrations according to Eur. Ph.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 1","pages":"165-175"},"PeriodicalIF":2.8,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive overview of selective and novel fibroblast growth factor receptor inhibitors as a potential anticancer modality.","authors":"Nem Kumar Jain, Mukul Tailang, Neelaveni Thangavel, Hafiz A Makeen, Mohammed Albratty, Asim Najmi, Hassan Ahmad Alhazmi, Khalid Zoghebi, Muthumanickam Alagusundaram, Hemant Kumar Jain, Balakumar Chandrasekaran","doi":"10.2478/acph-2024-0005","DOIUrl":"10.2478/acph-2024-0005","url":null,"abstract":"<p><p>The arrival of comprehensive genome sequencing has accelerated the understanding of genetically aberrant advanced cancers and target identification for possible cancer treatment. Fibroblast growth factor receptor (FGFR) gene alterations are frequent findings in various rare and advanced cancers refractive to mainstay chemo-therapy or surgical interventions. Several FGFR inhibitors have been developed for addressing these genetically altered FGFR-harboring malignancies, and some have performed well in clinical trials. In contrast, others are still being investigated in different phases of clinical trials. FDA has approved four anticancer agents such as erdafitinib, pemigatinib, infigratinib, and futibatinib, for clinical use in oncogenic FGFR-driven malignancies. These include cholangiocarcinoma, urothelial carcinoma, and myeloid/lymphoid malignancies. Pemigatinib is the only FGFR inhibitor globally approved (USA, EU, and Japan) and available as a targeted therapy for two types of cancer, including FGFR2 fusion or other rearrangements harboring cholangiocarcinoma and relapsed/refractory myeloid/lymphoid neoplasms with FGFR1 rearrangements. Myeloid/lymphoid neoplasm is the latest area of application added to the therapeutic armamentarium of FGFR inhibitors. Furthermore, futibatinib is the first-in-class covalent or irreversible pan-FGFR inhibitor that has received FDA approval for locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene aberrations. This review highlights the current clinical progress concerning the safety and efficacy of all the approved FGFR-TKIs (tyrosine kinase inhibitors) and their ongoing investigations in clinical trials for other oncogenic FGFR-driven malignancies.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 1","pages":"1-36"},"PeriodicalIF":2.8,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}