Diabetes Drugs: Present and Emerging

Tilley, Jefferson; Grimsby, Joseph; Erickson, Shawn D.; Berthel, Steven J.

doi:10.1002/0471266949.bmc198

Cited by 4 publications

(3 citation statements)

References 203 publications

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“…Metformin is almost completely in a protonated cationic form under physiological conditions due to its strong basicity (pK a = 12.4). 211 Along with the substantial hydrophilicity caused by its biguanide structure, it is not likely that metformin can be taken up by passive diffusion. In fact, the cellular uptake of metformin largely relies on membrane transporters like organic cation transporters (OCTs); 212 thus, the expression level of OCTs in different tissues and different tumor types will greatly influence its absorption, distribution, and efficacy.…”

Section: ■ Oxphos Inhibitors In Clinical Trialsmentioning

confidence: 99%

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Why All the Fuss about Oxidative Phosphorylation (OXPHOS)?

Xue

Bankhead

et al. 2020

J. Med. Chem.

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Certain subtypes of cancer cells require oxidative phosphorylation (OXPHOS) to survive. Increased OXPHOS dependency is frequently a hallmark of cancer stem cells and cells resistant to chemotherapy and targeted therapies. Suppressing the OXPHOS function might also influence the tumor microenvironment by alleviating hypoxia and improving the antitumor immune response. Thus, targeting OXPHOS is a promising strategy to treat various cancers. A growing arsenal of therapeutic agents is under development to inhibit this biological process. This Perspective provides an overview of the structure and function of OXPHOS complexes, their biological functions in cancer, relevant research tools and models, as well as the limitations of OXPHOS as drug targets. We also focus on the current development status of OXPHOS inhibitors and potential therapeutic strategies to strengthen their clinical applications.

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Section: ■ Oxphos Inhibitors In Clinical Trialsmentioning

confidence: 99%

“…Metformin is almost completely in a protonated cationic form under physiological conditions due to its strong basicity (p K a = 12.4) . Along with the substantial hydrophilicity caused by its biguanide structure, it is not likely that metformin can be taken up by passive diffusion.…”

Section: Oxphos Inhibitors In Clinical Trialsmentioning

confidence: 99%

Why All the Fuss about Oxidative Phosphorylation (OXPHOS)?

Xue

Bankhead

et al. 2020

J. Med. Chem.

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“…Metformin and Crown were employed as the additives to synergistic regulation of the defect passivation and QW width distribution of the quasi‐2D perovskites, and their chemical structures are shown in Figure a. Metformin is a strong base with a pKa of ≈12.4, [ 24 ] and it may interact strongly with the Lewis acid Pb 2+ ion. Crown with unique pore structures are typical selective coordination compounds, and their coordination ability is strongly dependent on the matching degree between the pore size and ionic radius.…”

Section: Resultsmentioning

confidence: 99%

High‐Efficiency Quasi‐2D Perovskite Light‐Emitting Diodes Using a Dual‐Additive Strategy Guided by Preferential Additive‐Precursor Interactions

Tang

Guo

et al. 2023

Advanced Optical Materials

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The semi-conductive inorganic perovskite layer sandwiched between wide band-gap organic layers with low dielectric constant forms a quantum well-like structure in energies, and the introduced dielectric and quantum confinement effects also favor to enhance the exciton binding energy and boost the radiative recombination efficiency. [7][8][9] Although these outstanding optoelectronic properties have led to a big success in the quasi-2D perovskite LEDs, vacancy-induced defect states and insufficient energy transfer between the multiple quantum wells still impede the efficient radiative recombination in the quasi-2D perovskites. The abundant defects induced by uncoordinated lead (II) (Pb 2+ ) ions in the polycrystalline perovskite films would cause severe nonradiative recombination losses. [10][11][12] The heterogeneous QW width distribution of the quasi-2D perovskites would lead to an incomplete energy transfer from the wide-bandgap phase to the narrow-bandgap phase, which compromises the optical and electrical properties of the resultant material. [13][14][15] Functional additives have been widely used to regulate the quality of quasi-2D perovskite, such as the QW width distribution and the defect density, [16][17][18] which becomes a powerful tool for enhancing the performance of the PeLEDs. Previous studies have focused on the effects of synergistic interactions through additives and antisolvents towards regulating the crystal nucleation and growth, reducing the defects at grain boundaries, and reconfiguring the QW width distribution. [19][20][21][22] However, the additive engineering combined with antisolvent-assisted crystallization is extremely sensitive to the processing conditions and thus is not suitable for the batchto-batch large-scale manufacturing. The use of dual additives with C-O-C bonds achieved a significant progress in the fabrication of high-efficiency PeLEDs without anti-solvent treatment. The dual additives induced to form the perovskite nanocrystals with a defect-reduced quasi-core-shell structure by inhibiting the self-aggregation of organic ligands, and the resultant green PeLEDs achieved a maximum external quantum efficiency (EQE) of 28%. [23] Typically, the multifunctional additives would Quasi-2D perovskites are promising emitters in light-emitting diodes (LEDs) due to their natural quantum well (QW) structure and tunable exciton binding energy. Synergistic regulation of the defect passivation and QW width distribution of quasi-2D perovskites is crucial to achieve highperformance perovskite-based LEDs. Herein, a combination of two additives, i.e., 3-(diaminomethylidene)-1,1-dimethylguanidine (Metformin) and 1,4,7,10,13,16-hexaoxacyclooctadecane (Crown) having preferential interactions with different quasi-2D perovskite precursors is proposed to synergistically passivate the defects and regulate the QW width distribution of quasi-2D perovskites. Metformin additive interacts strongly with lead bromide, mainly passivating the defects. Crown additive has preferential interactions with organi...

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Sodium Glucose Cotransporter Inhibitors for the Treatment of Diabetes

Jesus

Harrison²,

Dore

2021

Burger's Medicinal Chemistry and Drug Discovery

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Worldwide, the incidence of diabetes mellitus, a chronic metabolic disease that results in four million deaths from it and associated complications annually, is increasing and its treatment is an enormous public health concern. Type 1 diabetes is treated by insulin, but a variety of drugs are used to treat the more prevalent type 2 diabetes. Inhibitors of sodium glucose cotransporters (SGLTs) are the newest drugs to reach the market to achieve the blood‐glucose control needed to treat type 2 diabetes. SGLT1 and 2 carry out renal reabsorption of more than 90% of glucose from urine against a concentration gradient using the electrochemical energy from the cotransport of sodium ions. Blocking SGLTs causes excess glucose to be excreted through the urine, reducing blood sugar. The first known SGLT inhibitor was the O ‐glycosylated flavonoid natural product phlorizin, which enabled the discovery of SGLTs and served as the initial lead compound for medicinal chemistry. O ‐ and C ‐Glycosylated flavonoid and dihydrochalcone natural products also inhibit SGLTs. The drugs on the market today, dapagliflozin, canagliflozin, empagliflozin, ertugliflozin, and others, are all aryl C ‐glycosides. They are selective for SGLT2 over SGLT1 to avoid adverse side effects associated with SGLT1 inhibition. Studies have suggested that SGLT inhibitors have a renal and cardiovascular protective effect that is advantageous, although their use increases the risk of urinary tract and genital infections and ketoacidosis. SGLT inhibitors are in trials as an adjuvant to insulin for the treatment of type 1 diabetes.

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Diabetes Drugs: Present and Emerging

Cited by 4 publications

References 203 publications

Why All the Fuss about Oxidative Phosphorylation (OXPHOS)?

Why All the Fuss about Oxidative Phosphorylation (OXPHOS)?

High‐Efficiency Quasi‐2D Perovskite Light‐Emitting Diodes Using a Dual‐Additive Strategy Guided by Preferential Additive‐Precursor Interactions

Sodium Glucose Cotransporter Inhibitors for the Treatment of Diabetes

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