ofloxacin and atenolol

ofloxacin has been researched along with atenolol in 35 studies

Research

Studies (35)

TimeframeStudies, this research(%)All Research%
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's7 (20.00)29.6817
2010's23 (65.71)24.3611
2020's5 (14.29)2.80

Authors

AuthorsStudies
Carrupt, PA; Crivori, P; Cruciani, G; Testa, B1
Benz, RD; Contrera, JF; Kruhlak, NL; Matthews, EJ; Weaver, JL1
Bellows, DS; Clarke, ID; Diamandis, P; Dirks, PB; Graham, J; Jamieson, LG; Ling, EK; Sacher, AG; Tyers, M; Ward, RJ; Wildenhain, J1
Lombardo, F; Obach, RS; Waters, NJ1
Ahlin, G; Artursson, P; Bergström, CA; Gustavsson, L; Karlsson, J; Larsson, R; Matsson, P; Norinder, U; Pedersen, JM1
Andrisano, V; Barril, X; Bartolini, M; Carreiras, Mdo C; de los Ríos, C; García, AG; Huertas, O; León, R; López, B; López, MG; Luque, FJ; Marco-Contelles, J; Rodríguez-Franco, MI; Samadi, A; Villarroya, M1
Chupka, J; El-Kattan, A; Feng, B; Miller, HR; Obach, RS; Troutman, MD; Varma, MV1
Campillo, NE; Guerra, A; Páez, JA1
Chang, G; El-Kattan, A; Miller, HR; Obach, RS; Rotter, C; Steyn, SJ; Troutman, MD; Varma, MV1
Avdeef, A; Tam, KY1
Brea, J; Cadavid, MI; Campillo, NE; Ceballos, P; Gil, C; Loza, MI; Martínez, A; Moro, MA; Pérez, C; Pérez, DI; Perez-Castillo, A; Redondo, M; Val, C; Zarruk, JG1
Andrisano, V; Bolognesi, ML; Carloni, P; Cavalli, A; Chiriano, G; De Simone, A; Legname, G; Mancini, F; Martinez, A; Perez, DI; Roberti, M1
Alonso-Gil, S; Campillo, NE; Castro, A; Encinas, A; Gil, C; Martinez, A; Morales-Garcia, JA; Palomo, V; Perez, C; Perez, DI; Perez-Castillo, A; Soteras, I1
Artursson, P; Haglund, U; Karlgren, M; Kimoto, E; Lai, Y; Norinder, U; Vildhede, A; Wisniewski, JR1
Alonso-Gil, S; Chavarría, C; Gil, C; Morales Garcia, JA; Pérez, C; Perez, DI; Pérez-Castillo, A; Porcal, W; Souza, JM1
Afshari, CA; Chen, Y; Dunn, RT; Hamadeh, HK; Kalanzi, J; Kalyanaraman, N; Morgan, RE; van Staden, CJ1
Chen, J; Chen, X; Huang, L; Li, X; Sun, Y1
Bellman, K; Knegtel, RM; Settimo, L1
Bello, ML; Gil, C; Kraemer, BC; Lecourtois, M; Liachko, NF; Martinez, A; Miguel, L; Perez, C; Perez, DI; Redondo, M; Salado, IG1
Huang, L; Li, X; Meng, F; Miao, H; Sun, Y1
Chen, M; Hu, C; Suzuki, A; Thakkar, S; Tong, W; Yu, K1
Brodsky, JL; Chiang, A; Chung, WJ; Denny, RA; Goeckeler-Fried, JL; Havasi, V; Hong, JS; Keeton, AB; Mazur, M; Piazza, GA; Plyler, ZE; Rasmussen, L; Rowe, SM; Sorscher, EJ; Weissman, AM; White, EL1
Guo, QL; Huang, SL; Huang, ZS; Li, D; Liu, ZQ; Ou, TM; Tan, JH; Wang, HG; Wang, N; Wu, JQ; Xia, CL1
Campillo, NE; Geiger, L; Gil, C; González, S; Li, L; Martinez, A; Morales, AV; Perez, DI; Salado, IG; Sebastián-Pérez, V; Zaldivar-Diez, J1
Campillo, NE; Cañada, FJ; Canales, A; Carvalho, I; Chierrito, TPC; Martinez, A; Martínez-Gonzalez, L; Pedersoli-Mantoani, S; Perez, C; Pérez, DI; Roca, C; Sebastian-Pérez, V1
An, B; Hu, J; Huang, L; Li, X; Li, Z; Pan, T1
Balliano, TL; Barbosa, G; Carvalho, VF; da Silva, BA; de Souza, ET; Lima, LM; Martins, IRR; Martins, MA; Medeiros, MM; Moraes Junior, MO; Nunes, IKDC; Silva, PMR; Silva, SWD1
Abdel-Maksoud, MS; Ali, EMH; Ammar, UM; Choi, HS; El-Gamal, MI; Gamal El-Din, MM; Han, DK; Jeon, HR; Kim, G; Kwon, D; Kwon, YJ; Lee, BS; Lee, JK; Lee, KH; Lee, KT; Mersal, KI; Oh, CH; Yoo, KH1
Chen, H; Ding, H; Gao, Y; Jiang, X; Liu, W; Liu, X; Tian, L; Xu, Z; Zhao, Q1
Chaikuad, A; de Lago, E; Gil, C; Gomez-Almeria, M; Gonzalo-Consuegra, C; Knapp, S; Lietha, D; Martín-Requero, A; Martinez, A; Martínez-González, L; Monti, B; Nozal, V; Palomo, V; Pérez-Cuevas, E; Petralla, S; Ramírez, D; Santana, P1
Achilleos, A; Hapeshi, E; Kassinos, D; Mantzavinos, D; Michael, C; Vasquez, MI; Xekoukoulotakis, NP1
Álvarez, PM; Amat, AM; Beltrán, FJ; León, EA; Márquez, G; Rodríguez, EM1
Bracale, M; Bruno, A; De Mattia, F; Labra, M; Marsoni, M; Vannini, C1
Álvarez, PM; Beltrán, FJ; Márquez, G; Rodríguez, EM1
Chang, H; Chen, C; Du, H; Guan, C; Li, C; Qiu, L; Wang, S; Wang, T; Wu, Y; Zhang, L; Zhang, S; Zhou, H1

Reviews

1 review(s) available for ofloxacin and atenolol

ArticleYear
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
    Drug discovery today, 2016, Volume: 21, Issue:4

    Topics: Chemical and Drug Induced Liver Injury; Databases, Factual; Drug Labeling; Humans; Pharmaceutical Preparations; Risk

2016

Other Studies

34 other study(ies) available for ofloxacin and atenolol

ArticleYear
Predicting blood-brain barrier permeation from three-dimensional molecular structure.
    Journal of medicinal chemistry, 2000, Jun-01, Volume: 43, Issue:11

    Topics: Blood-Brain Barrier; Databases, Factual; Models, Chemical; Molecular Conformation; Multivariate Analysis; Permeability; Pharmaceutical Preparations; Pharmacokinetics; Structure-Activity Relationship

2000
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
    Current drug discovery technologies, 2004, Volume: 1, Issue:4

    Topics: Adverse Drug Reaction Reporting Systems; Artificial Intelligence; Computers; Databases, Factual; Drug Prescriptions; Drug-Related Side Effects and Adverse Reactions; Endpoint Determination; Models, Molecular; Quantitative Structure-Activity Relationship; Software; United States; United States Food and Drug Administration

2004
Chemical genetics reveals a complex functional ground state of neural stem cells.
    Nature chemical biology, 2007, Volume: 3, Issue:5

    Topics: Animals; Cell Survival; Cells, Cultured; Mice; Molecular Structure; Neoplasms; Neurons; Pharmaceutical Preparations; Sensitivity and Specificity; Stem Cells

2007
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
    Drug metabolism and disposition: the biological fate of chemicals, 2008, Volume: 36, Issue:7

    Topics: Blood Proteins; Half-Life; Humans; Hydrogen Bonding; Infusions, Intravenous; Pharmacokinetics; Protein Binding

2008
Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1.
    Journal of medicinal chemistry, 2008, Oct-09, Volume: 51, Issue:19

    Topics: Cell Line; Computer Simulation; Drug Design; Gene Expression Profiling; Humans; Hydrogen Bonding; Liver; Molecular Weight; Organic Cation Transporter 1; Pharmaceutical Preparations; Predictive Value of Tests; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Structure-Activity Relationship

2008
Tacripyrines, the first tacrine-dihydropyridine hybrids, as multitarget-directed ligands for the treatment of Alzheimer's disease.
    Journal of medicinal chemistry, 2009, May-14, Volume: 52, Issue:9

    Topics: Acetylcholinesterase; Alzheimer Disease; Amyloid beta-Peptides; Blood-Brain Barrier; Butyrylcholinesterase; Calcium; Calcium Channel Blockers; Catalytic Domain; Cell Death; Cell Line, Tumor; Cholinesterase Inhibitors; Cytosol; Dihydropyridines; Humans; Hydrogen Peroxide; Kinetics; Ligands; Models, Molecular; Peptide Fragments; Permeability; Tacrine

2009
Physicochemical determinants of human renal clearance.
    Journal of medicinal chemistry, 2009, Aug-13, Volume: 52, Issue:15

    Topics: Humans; Hydrogen Bonding; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Kidney; Metabolic Clearance Rate; Molecular Weight

2009
Neural computational prediction of oral drug absorption based on CODES 2D descriptors.
    European journal of medicinal chemistry, 2010, Volume: 45, Issue:3

    Topics: Administration, Oral; Humans; Models, Chemical; Neural Networks, Computer; Permeability; Quantitative Structure-Activity Relationship; Technology, Pharmaceutical

2010
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
    Journal of medicinal chemistry, 2010, Feb-11, Volume: 53, Issue:3

    Topics: Administration, Oral; Biological Availability; Humans; Intestinal Absorption; Pharmaceutical Preparations

2010
How well can the Caco-2/Madin-Darby canine kidney models predict effective human jejunal permeability?
    Journal of medicinal chemistry, 2010, May-13, Volume: 53, Issue:9

    Topics: Animals; Disease Models, Animal; Dogs; Humans; Jejunal Diseases; Kidney Diseases; Models, Biological; Permeability; Porosity; Regression Analysis

2010
Neuroprotective efficacy of quinazoline type phosphodiesterase 7 inhibitors in cellular cultures and experimental stroke model.
    European journal of medicinal chemistry, 2012, Volume: 47, Issue:1

    Topics: Animals; Blood-Brain Barrier; Cells, Cultured; Cyclic Nucleotide Phosphodiesterases, Type 7; Disease Models, Animal; Enzyme Inhibitors; Infarction, Middle Cerebral Artery; Male; Mice; Neuroprotective Agents; Permeability; Quinazolines; Stroke

2012
A small chemical library of 2-aminoimidazole derivatives as BACE-1 inhibitors: Structure-based design, synthesis, and biological evaluation.
    European journal of medicinal chemistry, 2012, Volume: 48

    Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid Precursor Protein Secretases; Animals; Cell Survival; Chickens; Humans; Imidazoles; Inhibitory Concentration 50; Magnetic Resonance Spectroscopy; Models, Molecular; Neurons; Small Molecule Libraries; Spectrometry, Mass, Electrospray Ionization; Spectroscopy, Fourier Transform Infrared; Structure-Activity Relationship

2012
5-imino-1,2,4-thiadiazoles: first small molecules as substrate competitive inhibitors of glycogen synthase kinase 3.
    Journal of medicinal chemistry, 2012, Feb-23, Volume: 55, Issue:4

    Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Astrocytes; Blood-Brain Barrier; Cell Death; Cell Differentiation; Cell Membrane Permeability; Cells, Cultured; Glycogen Synthase Kinase 3; Hippocampus; Humans; Imines; In Vitro Techniques; Lipopolysaccharides; Membranes, Artificial; Microglia; Models, Molecular; Neural Stem Cells; Neurogenesis; Neurons; Neuroprotective Agents; Nitrites; Protein Binding; Rats; Structure-Activity Relationship; Substrate Specificity; Swine; Thiadiazoles

2012
Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions.
    Journal of medicinal chemistry, 2012, May-24, Volume: 55, Issue:10

    Topics: Atorvastatin; Biological Transport; Drug Interactions; Estradiol; Estrone; HEK293 Cells; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; In Vitro Techniques; Least-Squares Analysis; Liver; Liver-Specific Organic Anion Transporter 1; Models, Molecular; Multivariate Analysis; Organic Anion Transporters; Organic Anion Transporters, Sodium-Independent; Protein Isoforms; Pyrroles; Solute Carrier Organic Anion Transporter Family Member 1B3; Structure-Activity Relationship; Transfection

2012
Microwave-assisted synthesis of hydroxyphenyl nitrones with protective action against oxidative stress.
    European journal of medicinal chemistry, 2012, Volume: 58

    Topics: Anti-Inflammatory Agents; Antioxidants; Blood-Brain Barrier; Cell Survival; Dose-Response Relationship, Drug; Humans; Microwaves; Molecular Structure; Neuroblastoma; Neuroprotective Agents; Nitrogen Oxides; Oxidative Stress; Oxidopamine; Peroxynitrous Acid; Structure-Activity Relationship; Tyrosine

2012
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
    Toxicological sciences : an official journal of the Society of Toxicology, 2013, Volume: 136, Issue:1

    Topics: Animals; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 11; ATP-Binding Cassette Transporters; Biological Transport; Chemical and Drug Induced Liver Injury; Cluster Analysis; Drug-Related Side Effects and Adverse Reactions; Humans; Liver; Male; Multidrug Resistance-Associated Proteins; Pharmacokinetics; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Risk Assessment; Risk Factors; Toxicity Tests

2013
Inhibition of cholinesterase and monoamine oxidase-B activity by Tacrine-Homoisoflavonoid hybrids.
    Bioorganic & medicinal chemistry, 2013, Dec-01, Volume: 21, Issue:23

    Topics: Alzheimer Disease; Animals; Blood-Brain Barrier; Cholinesterase Inhibitors; Cholinesterases; Electrophorus; Humans; Isoflavones; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Swine; Tacrine

2013
Comparison of the accuracy of experimental and predicted pKa values of basic and acidic compounds.
    Pharmaceutical research, 2014, Volume: 31, Issue:4

    Topics: Chemistry, Pharmaceutical; Forecasting; Hydrogen-Ion Concentration; Pharmaceutical Preparations; Random Allocation

2014
Protein kinase CK-1 inhibitors as new potential drugs for amyotrophic lateral sclerosis.
    Journal of medicinal chemistry, 2014, Mar-27, Volume: 57, Issue:6

    Topics: Amyotrophic Lateral Sclerosis; Animals; Animals, Genetically Modified; Benzothiazoles; Blood-Brain Barrier; Casein Kinase I; Cell Membrane Permeability; Cells, Cultured; DNA-Binding Proteins; Drosophila; Drug Design; Drug Discovery; HEK293 Cells; Heterocyclic Compounds; High-Throughput Screening Assays; Humans; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Conformation; Neurons; Neurotoxicity Syndromes; Phosphorylation; Protein Kinase Inhibitors; Substrate Specificity

2014
Discovery of indanone derivatives as multi-target-directed ligands against Alzheimer's disease.
    European journal of medicinal chemistry, 2014, Nov-24, Volume: 87

    Topics: Acetylcholinesterase; Alzheimer Disease; Amyloid beta-Peptides; Antioxidants; Blood-Brain Barrier; Butyrylcholinesterase; Cholinesterase Inhibitors; Drug Design; Humans; Indans; Inhibitory Concentration 50; Ligands; Peptide Fragments; Permeability; Protein Aggregates

2014
Increasing the Endoplasmic Reticulum Pool of the F508del Allele of the Cystic Fibrosis Transmembrane Conductance Regulator Leads to Greater Folding Correction by Small Molecule Therapeutics.
    PloS one, 2016, Volume: 11, Issue:10

    Topics: Alleles; Benzoates; Cells, Cultured; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Endoplasmic Reticulum; Furans; Gene Deletion; HEK293 Cells; HeLa Cells; High-Throughput Screening Assays; Humans; Hydroxamic Acids; Microscopy, Fluorescence; Protein Folding; Protein Structure, Tertiary; Pyrazoles; RNA, Messenger; Small Molecule Libraries; Ubiquitination; Vorinostat

2016
Design, synthesis and evaluation of 2-arylethenyl-N-methylquinolinium derivatives as effective multifunctional agents for Alzheimer's disease treatment.
    European journal of medicinal chemistry, 2017, Apr-21, Volume: 130

    Topics: Alzheimer Disease; Amyloid beta-Peptides; Antioxidants; Blood-Brain Barrier; Cell Death; Cell Line; Cholinesterase Inhibitors; Drug Design; Glutathione; Humans; Quinolines; Reactive Oxygen Species

2017
Leucine rich repeat kinase 2 (LRRK2) inhibitors based on indolinone scaffold: Potential pro-neurogenic agents.
    European journal of medicinal chemistry, 2017, Sep-29, Volume: 138

    Topics: Animals; Cell Differentiation; Cell Proliferation; Dose-Response Relationship, Drug; Humans; Indoles; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Mice; Mice, Inbred C57BL; Models, Molecular; Molecular Structure; Neural Stem Cells; Neuroprotective Agents; Protein Kinase Inhibitors; Structure-Activity Relationship

2017
Chameleon-like behavior of indolylpiperidines in complex with cholinesterases targets: Potent butyrylcholinesterase inhibitors.
    European journal of medicinal chemistry, 2018, Feb-10, Volume: 145

    Topics: Acetylcholinesterase; Butyrylcholinesterase; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Humans; Indoles; Molecular Structure; Piperidines; Structure-Activity Relationship

2018
Synthesis and evaluation of clioquinol-rolipram/roflumilast hybrids as multitarget-directed ligands for the treatment of Alzheimer's disease.
    European journal of medicinal chemistry, 2019, Feb-01, Volume: 163

    Topics: Alzheimer Disease; Aminopyridines; Animals; Benzamides; Clioquinol; Cyclic Nucleotide Phosphodiesterases, Type 4; Cyclopropanes; Drug Design; Humans; Ligands; Mice; Rats; Rolipram

2019
Discovery of sulfonyl hydrazone derivative as a new selective PDE4A and PDE4D inhibitor by lead-optimization approach on the prototype LASSBio-448: In vitro and in vivo preclinical studies.
    European journal of medicinal chemistry, 2020, Oct-15, Volume: 204

    Topics: Animals; Cyclic AMP; Cyclic Nucleotide Phosphodiesterases, Type 4; Drug Design; Enzyme Inhibitors; Humans; Hydrazones; Hypersensitivity; Lung; Male; Mice

2020
Discovery of New Imidazo[2,1-
    Journal of medicinal chemistry, 2021, 05-27, Volume: 64, Issue:10

    Topics: Animals; Binding Sites; Cell Line, Tumor; Cell Proliferation; Drug Evaluation, Preclinical; Drug Screening Assays, Antitumor; Drug Stability; Half-Life; Humans; Imidazoles; Melanoma; Mice; Mitogen-Activated Protein Kinase Kinases; Molecular Docking Simulation; Phosphorylation; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Structure-Activity Relationship; Sulfonamides; Thiazoles; Transplantation, Heterologous

2021
Design, synthesis and biological evaluation of harmine derivatives as potent GSK-3β/DYRK1A dual inhibitors for the treatment of Alzheimer's disease.
    European journal of medicinal chemistry, 2021, Oct-15, Volume: 222

    Topics: Alzheimer Disease; Cell Line; Cell Proliferation; Dose-Response Relationship, Drug; Drug Design; Dyrk Kinases; Glycogen Synthase Kinase 3 beta; Harmine; Humans; Models, Molecular; Molecular Structure; Neuroprotective Agents; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Protein-Tyrosine Kinases; Structure-Activity Relationship

2021
TDP-43 Modulation by Tau-Tubulin Kinase 1 Inhibitors: A New Avenue for Future Amyotrophic Lateral Sclerosis Therapy.
    Journal of medicinal chemistry, 2022, 01-27, Volume: 65, Issue:2

    Topics: Amyotrophic Lateral Sclerosis; Animals; Brain; Case-Control Studies; DNA-Binding Proteins; Humans; Inflammation; Macrophages; Male; Mice; Mice, Inbred BALB C; Mice, Transgenic; Phosphorylation; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Rats; Rats, Wistar; Spinal Cord; Tissue Distribution

2022
Drugs degrading photocatalytically: Kinetics and mechanisms of ofloxacin and atenolol removal on titania suspensions.
    Water research, 2010, Volume: 44, Issue:6

    Topics: Animals; Atenolol; Catalysis; Daphnia; Hydrogen Peroxide; Hydrogen-Ion Concentration; Kinetics; Minerals; Ofloxacin; Soil; Solutions; Suspensions; Titanium; Toxicity Tests; Ultraviolet Rays; Waste Disposal, Fluid; Water Supply

2010
Mechanism considerations for photocatalytic oxidation, ozonation and photocatalytic ozonation of some pharmaceutical compounds in water.
    Journal of environmental management, 2013, Sep-30, Volume: 127

    Topics: Adsorption; Atenolol; Environmental Restoration and Remediation; Hydrochlorothiazide; Hydrogen-Ion Concentration; Ofloxacin; Oxidation-Reduction; Oxygen; Ozone; Photochemical Processes; Semiconductors; Titanium; Trimethoprim; Ultraviolet Rays; Water Pollutants, Chemical

2013
Uptake and effects of a mixture of widely used therapeutic drugs in Eruca sativa L. and Zea mays L. plants.
    Ecotoxicology and environmental safety, 2014, Volume: 108

    Topics: Albuterol; Atenolol; Bezafibrate; Brassicaceae; Carbamazepine; Cyclophosphamide; Drug Interactions; Germination; Humans; Lincomycin; Ofloxacin; Pharmaceutical Preparations; Ranitidine; Rivers; Tandem Mass Spectrometry; Wastewater; Water Pollutants, Chemical; Zea mays

2014
Solar photocatalytic ozonation of a mixture of pharmaceutical compounds in water.
    Chemosphere, 2014, Volume: 113

    Topics: Atenolol; Biodegradation, Environmental; Catalysis; Hydrochlorothiazide; Models, Chemical; Molecular Structure; Ofloxacin; Oxidation-Reduction; Ozone; Pharmaceutical Preparations; Photolysis; Sunlight; Titanium; Trimethoprim; Wastewater; Water Pollutants, Chemical; Water Purification

2014
Effects of membrane transport activity and cell metabolism on the unbound drug concentrations in the skeletal muscle and liver of drugs: A microdialysis study in rats.
    Pharmacology research & perspectives, 2021, Volume: 9, Issue:5

    Topics: Animals; Antipyrine; Atenolol; Carbamazepine; Cell Membrane; Digoxin; Diltiazem; Diphenhydramine; Drug Elimination Routes; Gabapentin; Lamotrigine; Liver; Memantine; Membrane Transport Proteins; Microdialysis; Muscle, Skeletal; Ofloxacin; Pharmaceutical Preparations; Propranolol; Pyrilamine; Quinidine; Rats; Terfenadine

2021