692,227 results match your criteria inhibitor


Neonatal Withdrawal Syndrome following Late in utero Exposure to Selective Serotonin Reuptake Inhibitors: A Systematic Review and Meta-Analysis of Observational Studies.

Psychother Psychosom 2021 May 10:1-9. Epub 2021 May 10.

Department of Health Sciences, University of Florence, Florence, Italy.

Introduction: A clear picture of neonatal withdrawal signs due to in utero selective serotonin reuptake inhibitor (SSRI) exposure and its consequences is still missing.

Objective: A systematic review and a meta-analysis were performed to provide an overview of neonatal withdrawal signs following late in utero exposure to SSRIs and to quantify the corresponding risks.

Methods: MEDLINE, Web of Science, and Embase were searched from inception to January 2021. Read More

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VDAC1 as a target in cisplatin anti-tumor activity through promoting mitochondria fusion.

Biochem Biophys Res Commun 2021 May 7;560:52-58. Epub 2021 May 7.

Key Laboratory of Molecular Epidemiology of Hunan Province, School of Medicine, Hunan Normal University, Changsha, 410081, PR China. Electronic address:

Cisplatin is one of the most effective anti-cancer drugs, but its efficacy is limited by the development of resistance. Previous studies have shown that mitochondria play critical roles in cisplatin cytotoxicity, however, the exact mechanism of mitochondria involved in cisplatin sensitivity has not been clarified. In this study, cisplatin triggered mitochondrial oxidative stress and the decrease of mitochondria membrane potential in human cervical cancer cells. Read More

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LPS decreases CFTR open probability and mucociliary transport through generation of reactive oxygen species.

Redox Biol 2021 Apr 30;43:101998. Epub 2021 Apr 30.

Department of Otolaryngology Head & Neck Surgery, University of Alabama at Birmingham, Birmingham, AL, USA; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address:

Lipopolysaccharide (LPS) serves as the interface between gram-negative bacteria (GNB) and the innate immune response in respiratory epithelial cells (REC). Herein, we describe a novel biological role of LPS that permits GNB to persist in the respiratory tract through inducing CFTR and mucociliary dysfunction. LPS reduced cystic fibrosis transmembrane conductance regulater (CFTR)-mediated short-circuit current in mammalian REC in Ussing chambers and nearly abrogated CFTR single channel activity (defined as forskolin-activated Cl currents) in patch clamp studies, effects of which were blocked with toll-like receptor (TLR)-4 inhibitor. Read More

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Discovery of myricetin as an inhibitor against Streptococcus mutans and an anti-adhesion approach to biofilm formation.

Int J Med Microbiol 2021 May 5;311(4):151512. Epub 2021 May 5.

Center of Stomatology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, No. 1095, Jiefang Road, Wuhan, Hubei, People's Republic of China; School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China. Electronic address:

Streptococcus mutans (S. mutans) are cariogenic microorganisms. Sortase A (SrtA) is a transpeptidase that attaches Pac to the cell surface. Read More

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Design, synthesis and biological evaluation of imidazopyridazine derivatives containing isoquinoline group as potent MNK1/2 inhibitors.

Bioorg Med Chem 2021 May 2;40:116186. Epub 2021 May 2.

Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address:

Mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are located at the meeting-point of ERK and p38 MAPK signaling pathways, which can phosphorylate eukaryotic translation initiation factor 4E (eIF4E) at the conserved serine 209 exclusively. MNKs modulate the translation of mRNA involved in tumor-associated signaling pathways. Consequently, selective inhibitors of MNK1/2 could reduce the level of phosphorylated eIF4E. Read More

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Discovery of novel tripeptide propylene oxide proteasome inhibitors for the treatment of multiple myeloma.

Bioorg Med Chem 2021 May 1;40:116182. Epub 2021 May 1.

College of Life Science, Nanjing Normal University, No. 1 Wenyuan Road, Nanjing 210037, PR China; Jiangsu Chia Tai Fenghai Pharmaceutical Co. Ltd., No. 9 Weidi Road, Nanjing 210046, PR China. Electronic address:

The ubiquitin proteasome pathway (UPP) plays a critical role in the maintenance of cell homeostasis and the development of diseases, such as cancer and neurodegenerative disease. A series of novel tripeptide propylene oxide compounds as proteasome inhibitors were designed, synthesized and biologically investigated in this manuscript. The enzymatic activities of final compounds against 20S human proteasome were investigated and structure-activity relationship (SAR) was summarized. Read More

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Innovative use of σ and π electron acceptors in the development of three high throughput 96-microwell spectrophotometric assays for crizotinib.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Apr 30;259:119884. Epub 2021 Apr 30.

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.

Crizotinib (CZT) is a potent and selective tyrosine kinase inhibitor used for treatment of non-small cell lung cancer (NSCLC). The development of high-throughput assays for its quality control (QC) is very essential to assure its therapeutic benefits. CZT molecule has multiple electron-donating atoms that can contribute to the formation of colored charge-transfer (CT) complex with iodine as σ-electron acceptor and with 2,5-dichloro-3,6-dihydroxy-1,4-benzoquinone (CHBQ) and 7,7,8,8-tetracyanoquinodimethane (TCNQ) as π-electron acceptors. Read More

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KRAS secondary mutations that confer acquired resistance to KRAS G12C inhibitors, sotorasib and adagrasib, and overcoming strategies: insights from the in vitro experiments.

J Thorac Oncol 2021 May 7. Epub 2021 May 7.

Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan. Electronic address:

Introduction: KRAS mutations have been recognized as undruggable for many years. Recently, novel KRAS G12C inhibitors such as sotorasib and adagrasib are being developed in clinical trials and have shown promising results in metastatic non-small cell lung cancer. However, it is strongly anticipated that acquired resistance will limit their clinical utility. Read More

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Constitutive JAK/STAT signaling is the primary mechanism of resistance to JAKi in TYK2-rearranged acute lymphoblastic leukemia.

Cancer Lett 2021 May 7. Epub 2021 May 7.

Cancer Program, Precision Medicine Theme, South Australian Health & Medical Research Institute (SAHMRI), Adelaide, Australia; Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia; Faculty of Sciences, University of Adelaide, Adelaide, Australia; Australian Genomics Health Alliance (AGHA), Australia. Electronic address:

Activating TYK2-rearrangements have recently been identified and implicated in the leukemogenesis of high-risk acute lymphoblastic leukemia (HR-ALL) cases. Pre-clinical studies indicated the JAK/TYK2 inhibitor (JAKi), cerdulatinib, as a promising therapeutic against TYK2-rearranged ALL, attenuating the constitutive JAK/STAT signaling resulting from the TYK2 fusion protein. However, following a period of clinical efficacy, JAKi resistance often occurs resulting in relapse. Read More

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PDGF-PDGFR network differentially regulates, myogenic cell fate, migration, proliferation, and cell cycle progression.

Cell Signal 2021 May 7:110036. Epub 2021 May 7.

Departamento de Biología Celular y Molecular and Center for Aging and Regeneration (CARE-ChileUC), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile; Fundación Ciencia & Vida, 7780272 Santiago, Chile.

Platelet-derived growth factors (PDGFs) regulate embryonic development, tissue regeneration, and wound healing through their binding to PDGF receptors, PDGFRα and PDGFRβ. However, the role of PDGF signaling in regulating muscle development and regeneration remains elusive, and the cellular and molecular responses of myogenic cells are understudied. Here, we explore the PDGF-PDGFR gene expression changes and their involvement in skeletal muscle myogenesis and myogenic fate. Read More

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A Differential Equation Based Modelling Approach to Predict Supersaturation and In Vivo Absorption from In Vitro Dissolution-Absorption System (idas2) Data.

Eur J Pharm Biopharm 2021 May 7. Epub 2021 May 7.

Absorption Systems, Exton, PA1 9341, USA. Electronic address:

In vitro dissolution tests are widely used to monitor the quality and consistency of oral solid dosage forms, but to increase the physiological relevance of in vitro dissolution tests, newer systems combine dissolution and permeation measurements. Some of these use artificial membranes while others (e.g. Read More

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Microemulsion-based gel for the transdermal delivery of rasagiline mesylate: In vitro and in vivo assessment for Parkinson's therapy.

Eur J Pharm Biopharm 2021 May 7. Epub 2021 May 7.

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai 400019, Maharashtra, India. Electronic address:

Rasagiline mesylate (RSM) is a selective and irreversible monoamine oxidase B inhibitor used for the treatment of Parkinson's disease (PD). However, its unfavorable biopharmaceutical properties, such as extensive degradation in the gastrointestinal tract and first-pass metabolism are responsible for its low oral bioavailability and suboptimal therapeutic efficacy. Here, we report the feasibility of delivering RSM via the transdermal route using RSM containing microemulsion-based gel (RSM-MEG) to achieve effective management of PD. Read More

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Hydrophobic and polar interactions of FDA-approved small protein kinase inhibitors with their target enzymes.

Authors:
Robert Roskoski

Pharmacol Res 2021 May 7:105660. Epub 2021 May 7.

Blue Ridge Institute for Medical Research 3754 Brevard Road, Suite 116, Box 19 Horse Shoe, North Carolina 28742-8814, United States. Electronic address:

Dysregulation and mutations of protein kinases play causal roles in many diseases including cancer. The KLIFS (kinase-ligand interaction fingerprint and structure) catalog includes 85 ligand binding-site residues occurring in both the small and large protein kinase lobes. Except for allosteric inhibitors, all FDA-approved drug-target enzyme complexes display hydrophobic interactions involving catalytic spine residue-6 (KLIFS-77), catalytic spine residue-7 (KLIFS-11), and catalytic spine residue-8 (KLIFS-15) within the small lobe and residues within the hinge-linker region (KLIFS-46-52). Read More

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Changes in the mesocorticolimbic pathway after low dose reserpine-treatment in Wistar and Spontaneously Hypertensive Rat (SHR): implications for cognitive deficits in a progressive animal model for Parkinson's Disease.

Behav Brain Res 2021 May 7:113349. Epub 2021 May 7.

Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil. Electronic address:

Reserpine (RES) is an irreversible inhibitor of VMAT2 used to study Parkinson's disease (PD) and screening for antiparkinsonian treatments in rodents. Recently, the repeated treatment with a low dose of reserpine was proposed as a model capable of emulating progressive neurochemical, motor and non-motor impairments in PD. Conversely, compared to Wistar rats, Spontaneously Hypertensive Rats (SHR) are resistant to motor changes induced by repeated treatment with a low dose of RES. Read More

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Evaluation of heptelidic acid as a potential inhibitor for tau aggregation-induced Alzheimer's disease and associated neurotoxicity.

Int J Biol Macromol 2021 May 7. Epub 2021 May 7.

Department of Nanotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. Electronic address:

Tau is a major component of protein plaques in tauopathies, especially Alzheimer's disease (AD). The purpose of the present study is to explore the inhibitory effects of heptelidic acid as a bioactive compound from fungus T. koningii on tau fibrillization and associated neurotoxicity. Read More

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Melatonin Postconditioning Ameliorates Anoxia/Reoxygenation Injury by Regulating Mitophagy and Mitochondrial Dynamics in a SIRT3-Dependent Manner.

Eur J Pharmacol 2021 May 7:174157. Epub 2021 May 7.

Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University-Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, People's Republic of China. Electronic address:

Ischaemia/reperfusion (I/R) injury is accompanied by excessive mitochondrial autophagy (mitophagy) and an imbalance in mitochondrial dynamics. Melatonin has been reported to alleviate I/R injury by regulating mitophagy and mitochondrial dynamics. However, the underlying mechanism associated with this activity is not fully understood. Read More

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Methylglyoxal augments uridine diphosphate-induced contraction via activation of p38 mitogen-activated protein kinase in rat carotid artery.

Eur J Pharmacol 2021 May 7:174155. Epub 2021 May 7.

Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo, 142-8501, Japan. Electronic address:

The methylglyoxal elicits diverse adverse effects on the body. Uridine diphosphate, an extracellular nucleotide, plays an important role as a signaling molecule controlling vascular tone. This study aimed to evaluate the relationship between methylglyoxal and uridine diphosphate-induced carotid arterial contraction in rats. Read More

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Structures of human peptidylarginine deiminase type III provide insights into substrate recognition and inhibitor design.

Arch Biochem Biophys 2021 May 7:108911. Epub 2021 May 7.

Graduate School of Science and Engineering, Ibaraki University, Hitachi, Japan; Frontier Research Center for Applied Atomic Sciences, Ibaraki University, Tokai Naka, Japan. Electronic address:

Peptidylarginine deiminase type III (PAD3) is an isozyme belonging to the PAD enzyme family that converts arginine to citrulline residue(s) within proteins. PAD3 is expressed in most differentiated keratinocytes of the epidermis and hair follicles, while S100A3, trichohyalin, and filaggrin are its principal substrates. In this study, the X-ray crystal structures of PAD3 in six states, including its complex with the PAD inhibitor Cl-amidine, were determined. Read More

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Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial.

Lancet 2021 May 7. Epub 2021 May 7.

Research, Aurinia Pharmaceuticals, Victoria, BC, Canada. Electronic address:

Background: Voclosporin, a novel calcineurin inhibitor approved for the treatment of adults with lupus nephritis, improved complete renal response rates in patients with lupus nephritis in a phase 2 trial. This study aimed to evaluate the efficacy and safety of voclosporin for the treatment of lupus nephritis.

Methods: This multicentre, double-blind, randomised phase 3 trial was done in 142 hospitals and clinics across 27 countries. Read More

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Nur77 Attenuates Inflammasome Activation by Inhibiting Caspase-1 Expression in Pulmonary Vascular Endothelial Cells.

Am J Respir Cell Mol Biol 2021 May 10. Epub 2021 May 10.

Thomas Jefferson University, 6559, Philadelphia, Pennsylvania, United States;

Inflammasomes are intracellular multiprotein complexes that help trigger and maintain the inflammatory response as part of the innate immune system. Recently, it has been increasingly recognized that aberrant inflammasome activation is critically involved endothelial dysfunction in a variety of human diseases, such as atherosclerosis, acute lung injury (ALI), and type 2 diabetes. The molecular mechanisms underlying endothelial inflammasome activation, however, are not completely elucidated. Read More

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A Proteasome Mutation Sensitizes Cam3.II K13 Parasites to DHA and OZ439.

ACS Infect Dis 2021 May 10. Epub 2021 May 10.

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States.

Artemisinin-based combination therapies (ACTs), the World Health Organization-recommended first-line therapy for uncomplicated falciparum malaria, has led to significant decreases in malaria-associated morbidity and mortality in the past two decades. Decreased therapeutic efficacy of artemisinins, the cornerstone of ACTs, is threatening the gains made against this disease. As such, novel therapeutics with uncompromised mechanisms of action are needed to combat parasite-mediated antimalarial resistance. Read More

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Regulating Twisted Skeleton to Construct Organ-Specific Perylene for Intensive Cancer Chemotherapy.

Angew Chem Int Ed Engl 2021 May 10. Epub 2021 May 10.

National Center for Nanoscience and Technology, No. 11 Beiyitiao, Zhongguancun, 100190, Beijing, CHINA.

The systemic use of pharmaceutical drugs for cancer patients is a compromise between desirable therapy and side effects because of the intrinsic shortage of organ-specific pharmaceutical drug. Design and construction of pharmaceutical drug to achieve the organ-specific delivery is thus desperately desirable. We herein regulate perylene skeleton to effect organ-specificity and present an example of lung-specific distribution on the basis of bay-twisted PDIC-NC. Read More

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Overcoming TKI resistance in a patient with chronic myeloid leukemia using combination BCR-ABL inhibition with asciminib and bosutinib.

Am J Hematol 2021 May 10. Epub 2021 May 10.

Winship Cancer Institute of Emory University, Bone Marrow and Stem Cell Transplant Center, Atlanta, GA.

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The efficacy of elobixibat as bowel preparation agent for colonoscopy: A prospective, randomized, multi-center study.

Dig Endosc 2021 May 10. Epub 2021 May 10.

Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.

Background And Aim: Elobixibat is a novel ileal bile acid transporter inhibitor. This study aimed to compare the efficacy, tolerability, and safety of the combination of elobixibat and 1 L of polyethylene glycol formulation containing ascorbic acid (PEG-Asc) solution versus the combination of sodium picosulfate and 1-L PEG-Asc solution as bowel preparation for colonoscopy.

Methods: This multi-center, randomized, observer-blinded, non-inferiority study recruited 210 outpatients who were assigned to either the elobixibat plus 1-L PEG-Asc group (group A) or the sodium picosulfate plus 1-L PEG-Asc group (group B). Read More

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Patient, hospital and country-level risk factors of all-cause mortality among patients with chronic heart failure: Prospective international cohort study.

PLoS One 2021 10;16(5):e0250931. Epub 2021 May 10.

Maria Cecilia Hospital-GVM Care & Research, Cotignola, Italy.

Background: Although many studies have described patient-level risk factors for outcomes in heart failure (HF), health care structural determinants remain largely unexplored. This research reports patient-, hospital- and country-level characteristics associated with 1-year all-cause mortality among patients with chronic HF, and investigates geographic and hospital variation in mortality.

Methods And Findings: We included 9,277 patients with chronic HF enrolled between May 2011 and November 2017 in the prospective cohort study European Society of Cardiology Heart Failure Long Term registry across 142 hospitals, located in 22 countries. Read More

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Computational investigation of phytochemicals from (Indian ginseng/ashwagandha) as plausible inhibitors of GluN2B-containing NMDA receptors.

J Biomol Struct Dyn 2021 May 10:1-13. Epub 2021 May 10.

Division of Computer Aided Drug Design, Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India.

-Methyl-d-aspartate receptor (NMDAR)-mediated excitotoxicity has been implicated in multi-neurodegenerative diseases. Owing to dearth of efficacy and adverse effects of NMDA receptor antagonists, search for herbal remedies acting like salutary agents is a dynamic expanse of investigation to contest neurodegenerative disease. () has been used since antiquity as a nerve tonic and nootropic agents in Ayurveda, an old Indian system of medicine. Read More

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A higher flexibility at the SARS-CoV-2 main protease active site compared to SARS-CoV and its potentialities for new inhibitor virtual screening targeting multi-conformers.

J Biomol Struct Dyn 2021 May 10:1-21. Epub 2021 May 10.

Laboratory of Molecular Modeling and Bioinformatics, Department of Exact and Biological Sciences, Universidade Federal de São João Del Rei, Sete Lagoas, Brazil.

The main-protease (M) catalyzes a crucial step for the SARS-CoV-2 life cycle. The recent SARS-CoV-2 presents the main protease (M) with 12 mutations compared to SARS-CoV (M). Recent studies point out that these subtle differences lead to mobility variances at the active site loops with functional implications. Read More

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Risk of Ophthalmic Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis.

Ocul Immunol Inflamm 2021 May 10:1-11. Epub 2021 May 10.

Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

: Immune checkpoint inhibitors (ICIs) -induced adverse events (AEs) have been reported affecting almost all human organs. However, studies about ocular AEs are few. A meta-analysis was performed to evaluate the risks of ICI-related ophthalmic AEs compare to chemotherapy. Read More

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Phosphatidylinositol 3-kinase (PI3K) inhibitors: a recent update on inhibitor design and clinical trials (2016-2020).

Expert Opin Ther Pat 2021 May 10. Epub 2021 May 10.

DSC 362, Department of Chemistry, The University of Nebraska at Omaha, 6001 Dodge Street, Omaha, Nebraska 68182, USA.

Introduction: The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway plays a central role in regulating cell growth and proliferation and thus have been considered as effective anticancer drug targets. Many PI3K inhibitors have been developed and progressed to various stages of clinical trials and some even have been approved in recent years by the regulatory agency as anticancer treatment. In this review, we discuss the drug design and clinical development of PI3K inhibitors in the past four years. Read More

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Real-world treatment patterns and outcomes of abemaciclib for the treatment of HR+, HER2- metastatic breast cancer.

Curr Med Res Opin 2021 May 10. Epub 2021 May 10.

Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

This retrospective observational study described baseline characteristics, real-world treatment patterns, and outcomes among patients with metastatic breast cancer treated with abemaciclib in the United States. De-identified electronic health record-derived data were used to describe patients who began abemaciclib treatment on or after 30 June 2016 and ≥4 months before data cutoff (31 December 2018). Real-world response (rwR) and real-world progression assessments were abstracted from clinical documentation. Read More

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