Sensitization of cancer cells to paclitaxel-induced apoptosis by canagliflozin
Biochem Pharmacol. 2024 Mar 19:116140. doi: 10.1016/j.bcp.2024.116140. Online ahead of print.ABSTRACTCancer cells consume more glucose and usually overexpress glucose transporters which have become potential targets for the development of anticancer drugs. It has been demonstrated that selective SGLT2 inhibitors, such as canagliflozin and dapagliflozin, display anticancer activity. Here we demonstrated that canagliflozin and dapagliflozin synergistically enhanced the growth inhibitory effect of paclitaxel in cancer cells including ovarian cancer and oral squamous cell carcinoma cells. Canagliflozin also inhibited glucose u...
Source: Biochemical Pharmacology - March 21, 2024 Category: Drugs & Pharmacology Authors: Haoning Huang Fan-Lu Kung Yu-Wen Huang Chun-Chien Hsu Jih-Hwa Guh Lih-Ching Hsu Source Type: research

Synthetic approaches and clinical application of small-molecule inhibitors of sodium-dependent glucose transporters 2 for the treatment of type 2 diabetes mellitus
Eur J Med Chem. 2024 Mar 18;269:116343. doi: 10.1016/j.ejmech.2024.116343. Online ahead of print.ABSTRACTSodium-dependent glucose transporters 2 (SGLT2) inhibitors are a class of small-molecule drugs that have gained significant attention in recent years for their potential clinical applications in the treatment of type 2 diabetes mellitus (T2DM). These inhibitors function by obstructing the kidneys' ability to reabsorb glucose, resulting in a rise in the excretion of glucose in urine (UGE) and subsequently lowering blood glucose levels. Several SGLT2 inhibitors, such as Dapagliflozin, Canagliflozin, and Empagliflozin, hav...
Source: European Journal of Medicinal Chemistry - March 21, 2024 Category: Chemistry Authors: Tong Xie Li-Jie Zhao Source Type: research

Sensitization of cancer cells to paclitaxel-induced apoptosis by canagliflozin
Biochem Pharmacol. 2024 Mar 20;223:116140. doi: 10.1016/j.bcp.2024.116140. Online ahead of print.ABSTRACTCancer cells consume more glucose and usually overexpress glucose transporters which have become potential targets for the development of anticancer drugs. It has been demonstrated that selective SGLT2 inhibitors, such as canagliflozin and dapagliflozin, display anticancer activity. Here we demonstrated that canagliflozin and dapagliflozin synergistically enhanced the growth inhibitory effect of paclitaxel in cancer cells including ovarian cancer and oral squamous cell carcinoma cells. Canagliflozin also inhibited gluco...
Source: Biochemical Pharmacology - March 21, 2024 Category: Drugs & Pharmacology Authors: Haoning Huang Fan-Lu Kung Yu-Wen Huang Chun-Chien Hsu Jih-Hwa Guh Lih-Ching Hsu Source Type: research

Synthetic approaches and clinical application of small-molecule inhibitors of sodium-dependent glucose transporters 2 for the treatment of type 2 diabetes mellitus
Eur J Med Chem. 2024 Mar 18;269:116343. doi: 10.1016/j.ejmech.2024.116343. Online ahead of print.ABSTRACTSodium-dependent glucose transporters 2 (SGLT2) inhibitors are a class of small-molecule drugs that have gained significant attention in recent years for their potential clinical applications in the treatment of type 2 diabetes mellitus (T2DM). These inhibitors function by obstructing the kidneys' ability to reabsorb glucose, resulting in a rise in the excretion of glucose in urine (UGE) and subsequently lowering blood glucose levels. Several SGLT2 inhibitors, such as Dapagliflozin, Canagliflozin, and Empagliflozin, hav...
Source: European Journal of Medicinal Chemistry - March 21, 2024 Category: Chemistry Authors: Tong Xie Li-Jie Zhao Source Type: research

Adherence to newer second ‐line oral antidiabetic drugs among people with type 2 diabetes—A systematic review
The adherence to newer second-line oral antidiabetic drugs among people with type 2 diabetes was investigated in this study. A systematic literature search was performed in six databases. A total of 14948 records was retrieved from the databases of which 7 articles were included. The reported medication possession ratio (MPR) and treatment discontinuation was extracted from the articles, and these findings were visualised in figures and summarized in a narrative synthesis. The findings indicate that the adherence to the newer second-line OADs may be better than that of older OADs, but a study directly comparing older and n...
Source: Pharmacology Research and Perspectives - March 7, 2024 Category: Drugs & Pharmacology Authors: Nynne Sophie Holdt ‐Caspersen, Claus Dethlefsen, Peter Vestergaard, Ole Hejlesen, Stine Hangaard, Morten Hasselstrøm Jensen Tags: REVIEW Source Type: research

Implication of M2 macrophage on NLRP3 inflammasome signaling in mediating the neuroprotective effect of Canagliflozin against methotrexate-induced cognitive impairment
This study aimed to investigate CANA's protective effect against MTX-induced cognitive impairment, highlighting the possible involvement of TLR4/ NF-κB crosstalk with NLRP3 inflammasome activation and macrophage polarization. Forty-eight Male Wistar rats were divided into 4 groups; (1) received saline orally for 30 days and intravenously on days 8 and 15. (2) received Canagliflozin (CANA; 20 mg/kg/day; p.o.) for 30 days. (3) received MTX (75 mg/kg, i.v.) on day 8 and 15, then they were injected with four i.p. injections of leucovorin (LCV): the first dose was 6 mg/ kg after 18 h, and the remaining doses were 3 mg/kg after...
Source: International Immunopharmacology - February 20, 2024 Category: Allergy & Immunology Authors: Lobna H Khedr Rania M Rahmo Omar M Eldemerdash Engy M Helmy Felopateer A Ramzy George H Lotfy Habiba A Zakaria Marine M Gad Marina M Youhanna Manar H Samaan Nevert W Thabet Reem H Ghazal Mostafa A Rabie Source Type: research

Canagliflozin protects against hyperglycemia-induced cerebrovascular injury by preventing blood-brain barrier (BBB) disruption via AMPK/Sp1/adenosine A2A receptor
Eur J Pharmacol. 2024 Feb 8:176381. doi: 10.1016/j.ejphar.2024.176381. Online ahead of print.ABSTRACTDiabetes mellitus causes brain microvascular endothelial cell (MEC) damage, inducing dysfunctional angiogenic response and disruption of the blood-brain barrier (BBB). Canagliflozin is a revolutionary hypoglycemic drug that exerts neurologic and/or vascular-protective effects beyond glycemic control; however, its underlying mechanism remains unclear. In the present study, we hypothesize that canagliflozin ameliorates BBB permeability by preventing diabetes-induced brain MEC damage. Mice with high-fat diet/streptozotocin-ind...
Source: European Journal of Pharmacology - February 10, 2024 Category: Drugs & Pharmacology Authors: Zhiyi Liu Wei Hua Sinan Jin Yueying Wang Yuxin Pang Benshuai Wang Nan Zhao Jiping Qi Yuejia Song Source Type: research

Selective sodium-glucose cotransporter-2 inhibitors in the improvement of hemoglobin and hematocrit in patients with type 2 diabetes mellitus: a network meta-analysis
ConclusionBased on the existing studies, we concluded that SGLT2i could increase hematocrit and hemoglobin levels in patients with T2DM, and canagliflozin 100mg had the best effect on the improvement of hematocrit, while canagliflozin 200mg had the best effect on the improvement of hemoglobin.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#loginpage, identifier PROSPERO (CRD42023477103). (Source: Frontiers in Endocrinology)
Source: Frontiers in Endocrinology - February 1, 2024 Category: Endocrinology Source Type: research

Canagliflozin regulates metabolic reprogramming in diabetic kidney disease by inducing fasting-like and aestivation-like metabolic patterns
Conclusions/interpretationIn conclusion, our study shows that CANA ameliorates DKD by inducing fasting-like and aestivation-like metabolic patterns. Furthermore, DKD was ameliorated by glycine supplementation, and the beneficial effects of glycine were probably due to the activation of the AMPK/mTOR pathway.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - January 18, 2024 Category: Endocrinology Source Type: research

Identification of risk factors associated with acute kidney injury in patients taking sodium ‐glucose cotransporter‐2 inhibitors
ConclusionsThe transient eGFR decline with SGLT2 inhibitor initiation should be expected and is generally not an indication to discontinue therapy. Future initiatives should be directed at increasing knowledge of monitoring recommendations for these agents. (Source: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy)
Source: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy - January 12, 2024 Category: Drugs & Pharmacology Authors: Christie Schumacher, Amanda Chorpash, Charlotte Bolch, Kellye Eagan, Sara Nimer, Elizabeth Van  Dril Tags: RESEARCH ARTICLE Source Type: research

Canagliflozin attenuates kidney injury, gut-derived toxins, and gut microbiota imbalance in high-salt diet-fed Dahl salt-sensitive rats
CONCLUSION: Canagliflozin may change the production of metabolites and reduce the level of uremic toxins in the blood circulation by reconstructing the intestinal flora of DSS rats fed a high-salt diet, ultimately alleviating oxidative stress and renal injury.PMID:38189082 | DOI:10.1080/0886022X.2023.2300314 (Source: Renal Failure)
Source: Renal Failure - January 8, 2024 Category: Urology & Nephrology Authors: Lili He Qingjuan Zuo Sai Ma Guorui Zhang Zhongli Wang Tingting Zhang Jianlong Zhai Yifang Guo Source Type: research

Molecules, Vol. 29, Pages 273: Synthesis of New Derivatives of Berberine Canagliflozin and Study of Their Antibacterial Activity and Mechanism
ong Luo Hao Wei The isoquinoline alkaloid berberine, derived from Coptidis rhizoma, exhibits antibacterial, hypoglycemic, and anti-inflammatory properties. Canagliflozin is a sodium–glucose cotransporter 2 (SGLT2) inhibitor. We synthesized compounds B9OC and B9OBU by conjugating canagliflozin and n-butane at the C9 position of berberine, aiming to develop antimicrobial agents for combating bacterial infections worldwide. We utilized clinically prevalent pathogenic bacteria, namely Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, to investigate the antibacterial efficacy of B9OC. This...
Source: Molecules - January 4, 2024 Category: Chemistry Authors: Jinsheng Li Xueli Hou Jinlong Xiao Li Zhu Yujie Deng Ziyi Li Zijian Zhao Zhenghong Luo Hao Wei Tags: Article Source Type: research

Identification of Risk Factors Associated with Acute Kidney Injury in Patients Taking Sodium ‐Glucose Cotransporter‐2 Inhibitors
ConclusionsThe transient eGFR decline with SGLT2 inhibitor initiation should be expected and is generally not an indication to discontinue therapy. Future initiatives should be directed at increasing knowledge of monitoring recommendations for these agents. (Source: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy)
Source: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy - December 22, 2023 Category: Drugs & Pharmacology Authors: Christie Schumacher, Amanda Chorpash, Charlotte Bolch, Kellye Eagan, Sara Nimer, Elizabeth Van Dril Tags: RESEARCH ARTICLE Source Type: research

Comparative cardiovascular benefits of individual SGLT2 inhibitors in type 2 diabetes and heart failure: a systematic review and network meta-analysis of randomized controlled trials
ConclusionSGLT2is significantly reduce the composite CV death/HFH outcome. Among them, canagliflozin may be considered the preferred treatment for patients with diabetes and a history of heart failure, but it may also be associated with an increased risk of any adverse events compared to other SGLT2is. However, a sensitivity analysis focusing on HF-specific trials identified sotagliflozin as the most likely agent to reduce CV death/HFH, followed by empagliflozin and dapagliflozin.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022353754. (Source: Frontiers in Endocrinology)
Source: Frontiers in Endocrinology - December 20, 2023 Category: Endocrinology Source Type: research