PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 34541874-1 2022 OBJECTIVE: To evaluate the safety and efficacy of selumetinib, a novel MEK inhibitor, for the treatment of plexiform neurofibromas (PN) in patients with neurofibromatosis type 1 (NF1). AZD 6244 50-61 neurofibromin 1 Homo sapiens 153-177 28094260-0 2017 Targeted therapies: Selumetinib MEKing differences in NF1. AZD 6244 20-31 neurofibromin 1 Homo sapiens 54-57 28029918-2 2016 METHODS: We conducted a phase 1 trial of selumetinib (AZD6244 or ARRY-142886), an oral selective inhibitor of MAPK kinase (MEK) 1 and 2, in children who had neurofibromatosis type 1 and inoperable plexiform neurofibromas to determine the maximum tolerated dose and to evaluate plasma pharmacokinetics. AZD 6244 41-52 neurofibromin 1 Homo sapiens 157-181 28029918-14 2016 CONCLUSIONS: Our early-phase data suggested that children with neurofibromatosis type 1 and inoperable plexiform neurofibromas benefited from long-term dose-adjusted treatment with selumetinib without having excess toxic effects. AZD 6244 181-192 neurofibromin 1 Homo sapiens 63-87 22573716-3 2012 In 19 GBM cell lines, we found that treatment with the clinically available MEK inhibitors PD0325901 or AZD6244 decreased levels of phospho-ERK, the downstream effector of MEK, regardless of NF1 status. AZD 6244 104-111 neurofibromin 1 Homo sapiens 191-194 34196005-1 2021 Selumetinib (ARRY-142886), an oral, potent and highly selective allosteric MEK1/2 inhibitor, is approved by the US FDA for the treatment of pediatric patients aged 2 years and older with neurofibromatosis type 1 with symptomatic, inoperable plexiform neurofibromas. AZD 6244 0-11 neurofibromin 1 Homo sapiens 187-211 34196005-1 2021 Selumetinib (ARRY-142886), an oral, potent and highly selective allosteric MEK1/2 inhibitor, is approved by the US FDA for the treatment of pediatric patients aged 2 years and older with neurofibromatosis type 1 with symptomatic, inoperable plexiform neurofibromas. AZD 6244 13-24 neurofibromin 1 Homo sapiens 187-211 34604034-5 2021 One major advance is the FDA approval of the MEK inhibitor selumetinib for the treatment of NF1-associated plexiform neurofibroma. AZD 6244 59-70 neurofibromin 1 Homo sapiens 92-95 34541874-1 2022 OBJECTIVE: To evaluate the safety and efficacy of selumetinib, a novel MEK inhibitor, for the treatment of plexiform neurofibromas (PN) in patients with neurofibromatosis type 1 (NF1). AZD 6244 50-61 neurofibromin 1 Homo sapiens 179-182 35170228-1 2022 Selumetinib is an oral, potent, and highly selective allosteric MEK1/2 inhibitor approved for the treatment of pediatric patients (aged <=2 years) with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. AZD 6244 0-11 neurofibromin 1 Homo sapiens 152-176 34388689-6 2021 Selumetinib has shown an overall response rate of 68% in children with NF1 and symptomatic inoperable PNs, and was associated with pain improvement and a manageable adverse events profile. AZD 6244 0-11 neurofibromin 1 Homo sapiens 71-74 35467749-0 2022 Selumetinib in Children with Neurofibromatosis Type 1 and Asymptomatic Inoperable Plexiform Neurofibroma At Risk for Developing Tumor-Related Morbidity. AZD 6244 0-11 neurofibromin 1 Homo sapiens 29-53 35467749-1 2022 BACKGROUND: Selumetinib was recently approved for treatment of inoperable symptomatic plexiform neurofibromas (PNs) in children with neurofibromatosis type 1 (NF1). AZD 6244 12-23 neurofibromin 1 Homo sapiens 133-157 35467749-1 2022 BACKGROUND: Selumetinib was recently approved for treatment of inoperable symptomatic plexiform neurofibromas (PNs) in children with neurofibromatosis type 1 (NF1). AZD 6244 12-23 neurofibromin 1 Homo sapiens 159-162 35410754-1 2022 PURPOSE: Selumetinib (ARRY-142886) is an oral, potent, and highly selective allosteric mitogen-activated protein kinase kinase 1/2 inhibitor approved for the treatment of pediatric patients (>=2 years of age) with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. AZD 6244 9-20 neurofibromin 1 Homo sapiens 214-238 35410754-1 2022 PURPOSE: Selumetinib (ARRY-142886) is an oral, potent, and highly selective allosteric mitogen-activated protein kinase kinase 1/2 inhibitor approved for the treatment of pediatric patients (>=2 years of age) with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. AZD 6244 22-33 neurofibromin 1 Homo sapiens 214-238 35289492-0 2022 Selumetinib for symptomatic, inoperable plexiform neurofibromas in children with neurofibromatosis type 1: A national real-world case series. AZD 6244 0-11 neurofibromin 1 Homo sapiens 81-105 35301838-3 2022 EVIDENCE ACQUISITION: Articles describing the use of selumetinib in patients with neurofibromatosis type-1 (NF1) with inoperable plexiform neurofibromas were searched from different electronic databases. AZD 6244 53-64 neurofibromin 1 Homo sapiens 82-106 35301838-3 2022 EVIDENCE ACQUISITION: Articles describing the use of selumetinib in patients with neurofibromatosis type-1 (NF1) with inoperable plexiform neurofibromas were searched from different electronic databases. AZD 6244 53-64 neurofibromin 1 Homo sapiens 108-111 35301838-15 2022 CONCLUSIONS: Selumetinib can produce sustained shrinkage in the majority of patients with NF1 and symptomatic plexiform neurofibroma to provide clinically meaningful benefit in functional ability, with more robust evidence in children. AZD 6244 13-24 neurofibromin 1 Homo sapiens 90-93 35017312-0 2022 Efficacy and Safety of Selumetinib in Pediatric Patients With Neurofibromatosis Type 1: A Systematic Review and Meta-analysis. AZD 6244 23-34 neurofibromin 1 Homo sapiens 62-86 35017312-1 2022 BACKGROUND AND OBJECTIVES: Although the recent approval of selumetinib is expected to transform the management of children with Neurofibromatosis type 1 (NF1), particularly those with symptomatic and inoperable PN, no systematic review has summarized their efficacy and safety based on the latest studies. AZD 6244 59-70 neurofibromin 1 Homo sapiens 128-152 35017312-1 2022 BACKGROUND AND OBJECTIVES: Although the recent approval of selumetinib is expected to transform the management of children with Neurofibromatosis type 1 (NF1), particularly those with symptomatic and inoperable PN, no systematic review has summarized their efficacy and safety based on the latest studies. AZD 6244 59-70 neurofibromin 1 Homo sapiens 154-157 35017312-2 2022 This study was conducted to systematically evaluate the efficacy and safety of selumetinib in children with NF1 METHODS: Original articles reporting the efficacy and safety of selumetinib in patients with NF1 were identified in PubMed and EMBASE up to January 28, 2021. AZD 6244 79-90 neurofibromin 1 Homo sapiens 108-111 35017312-2 2022 This study was conducted to systematically evaluate the efficacy and safety of selumetinib in children with NF1 METHODS: Original articles reporting the efficacy and safety of selumetinib in patients with NF1 were identified in PubMed and EMBASE up to January 28, 2021. AZD 6244 176-187 neurofibromin 1 Homo sapiens 205-208 33903938-0 2021 Population pharmacokinetics and exposure-response of selumetinib and its N-desmethyl metabolite in pediatric patients with neurofibromatosis type 1 and inoperable plexiform neurofibromas. AZD 6244 53-64 neurofibromin 1 Homo sapiens 123-147 33683166-0 2021 Selumetinib: the first ever approved drug for neurofibromatosis-1 related inoperable plexiform neurofibroma. AZD 6244 0-11 neurofibromin 1 Homo sapiens 46-65 33683166-6 2021 Recently, the US Food and Drug Administration approved selumetinib for pediatric patients, 2 years of age and older, with neurofibromatosis type 1 who have symptomatic, inoperable tumor. AZD 6244 55-66 neurofibromin 1 Homo sapiens 122-146 33903938-1 2021 PURPOSE: Selumetinib (ARRY-142886) is a potent, selective, MEK1/2 inhibitor approved in the US for the treatment of children (>= 2 years) with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN). AZD 6244 9-20 neurofibromin 1 Homo sapiens 143-167 33903938-1 2021 PURPOSE: Selumetinib (ARRY-142886) is a potent, selective, MEK1/2 inhibitor approved in the US for the treatment of children (>= 2 years) with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN). AZD 6244 9-20 neurofibromin 1 Homo sapiens 169-172 33903938-1 2021 PURPOSE: Selumetinib (ARRY-142886) is a potent, selective, MEK1/2 inhibitor approved in the US for the treatment of children (>= 2 years) with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN). AZD 6244 22-33 neurofibromin 1 Homo sapiens 143-167 33903938-1 2021 PURPOSE: Selumetinib (ARRY-142886) is a potent, selective, MEK1/2 inhibitor approved in the US for the treatment of children (>= 2 years) with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN). AZD 6244 22-33 neurofibromin 1 Homo sapiens 169-172 33721151-6 2021 Selumetinib has become the first FDA-approved targeted therapy for NF1 following its demonstrated efficacy for inoperable plexiform neurofibroma. AZD 6244 0-11 neurofibromin 1 Homo sapiens 67-70 33712511-1 2021 On April 10, 2020, the U.S. Food and Drug Administration (FDA) approved selumetinib (KOSELUGO, AstraZeneca) for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). AZD 6244 72-83 neurofibromin 1 Homo sapiens 178-202 33712511-1 2021 On April 10, 2020, the U.S. Food and Drug Administration (FDA) approved selumetinib (KOSELUGO, AstraZeneca) for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). AZD 6244 72-83 neurofibromin 1 Homo sapiens 204-207 33354735-1 2021 Selumetinib, a highly specific mitogen-activated protein kinase 1/2 inhibitor, is approved for children older than 2 years of age with neurofibromatosis 1 who have inoperable plexiform neurofibromas. AZD 6244 0-11 neurofibromin 1 Homo sapiens 135-154 33549085-7 2021 The first case of peripheral edema occurred in a 7-year-old boy affected by a severe form of NF1, after two years of treatment with selumetinib at the standard dose (25 mg/m2twice a day). AZD 6244 132-143 neurofibromin 1 Homo sapiens 93-96 33978635-0 2021 Selumetinib normalizes Ras/MAPK signaling in clinically relevant neurofibromatosis type 1 minipig tissues in vivo. AZD 6244 0-11 neurofibromin 1 Homo sapiens 65-89 33978635-1 2021 Background: The MEK1/2 inhibitor selumetinib was recently approved for neurofibromatosis type 1 (NF1)-associated plexiform neurofibromas, but outcomes could be improved and its pharmacodynamic evaluation in other relevant tissues is limited. AZD 6244 33-44 neurofibromin 1 Homo sapiens 71-95 33978635-1 2021 Background: The MEK1/2 inhibitor selumetinib was recently approved for neurofibromatosis type 1 (NF1)-associated plexiform neurofibromas, but outcomes could be improved and its pharmacodynamic evaluation in other relevant tissues is limited. AZD 6244 33-44 neurofibromin 1 Homo sapiens 97-100 33978635-2 2021 The aim of this study was to assess selumetinib tissue pharmacokinetics (PK) and pharmacodynamics (PD) using a minipig model of NF1. AZD 6244 36-47 neurofibromin 1 Homo sapiens 128-131 33978635-6 2021 Selumetinib concentrations were higher in CNS tissues from NF1 compared to WT animals. AZD 6244 0-11 neurofibromin 1 Homo sapiens 59-62 33978635-8 2021 Basal p-ERK levels were significantly higher in NF1 minipig optic nerve compared to WT and were reduced to WT levels (60%) with selumetinib. AZD 6244 128-139 neurofibromin 1 Homo sapiens 48-51 33978635-10 2021 Conclusions: Selumetinib reduces MAPK signaling in tissues clinically relevant to NF1, effectively normalizing p-ERK to WT levels in optic nerve but resulting in abnormally low levels of p-ERK in the skin. AZD 6244 13-24 neurofibromin 1 Homo sapiens 82-85 33978635-11 2021 These results suggest that selumetinib exerts activity in NF1-associated CNS tumors by normalizing Ras/MAPK signaling and may explain common MEK inhibitor-associated dermatologic toxicities. AZD 6244 27-38 neurofibromin 1 Homo sapiens 58-61 32880495-11 2020 There are several highly successful non-NSCLC selumetinib trials involving, e.g., patients with neurofibromatosis type 1 related tumors and children with low-grade BRAF-driven gliomas. AZD 6244 46-57 neurofibromin 1 Homo sapiens 96-120 32601387-6 2020 We used dual-energy X-ray absorptiometry (DXA) to assess tumor-associated changes in bone mineral density (BMD) in an individual with NF1 following treatment with the MEK inhibitor selumetinib. AZD 6244 181-192 neurofibromin 1 Homo sapiens 134-137 32644232-1 2020 A 12-year-old girl with neurofibromatosis type 1 and a large facial plexiform neurofibroma had been participating in a selumetinib clinical trial for the past 5 years. AZD 6244 119-130 neurofibromin 1 Homo sapiens 24-48 32939452-0 2020 The MEK inhibitor selumetinib reduces spinal neurofibroma burden in patients with NF1 and plexiform neurofibromas. AZD 6244 18-29 neurofibromin 1 Homo sapiens 82-85 32939452-2 2020 The MEK inhibitor selumetinib shrinks the majority of plexiform neurofibromas (PNs) in patients with NF1. AZD 6244 18-29 neurofibromin 1 Homo sapiens 101-104 32272491-8 2020 The use of MEK inhibitors is likely to increase substantially with the expected upcoming approval of selumetinib for a specific indication for treatment of plexiform neurofibromas in NF1. AZD 6244 101-112 neurofibromin 1 Homo sapiens 183-186 32187457-13 2020 CONCLUSIONS: In this phase 2 trial, most children with neurofibromatosis type 1 and inoperable plexiform neurofibromas had durable tumor shrinkage and clinical benefit from selumetinib. AZD 6244 173-184 neurofibromin 1 Homo sapiens 55-79 32504375-2 2020 Selumetinib has been granted orphan drug status as adjuvant treatment for thyroid cancer (in the USA) and as treatment for neurofibromatosis type 1 (in the USA and the EU) and, based on the results of the phase II SPRINT trial, was recently approved in the USA in paediatric patients with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas. AZD 6244 0-11 neurofibromin 1 Homo sapiens 123-147 32504375-2 2020 Selumetinib has been granted orphan drug status as adjuvant treatment for thyroid cancer (in the USA) and as treatment for neurofibromatosis type 1 (in the USA and the EU) and, based on the results of the phase II SPRINT trial, was recently approved in the USA in paediatric patients with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas. AZD 6244 0-11 neurofibromin 1 Homo sapiens 289-313 32504375-3 2020 This article summarizes the milestones in the development of selumetinib leading to this first approval for the treatment of paediatric patients aged >= 2 years with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. AZD 6244 61-72 neurofibromin 1 Homo sapiens 166-190 31913576-5 2020 Through the conduct of a longitudinal cohort study and early phase clinical trials, the MEK inhibitor selumetinib was identified as the first active therapy for the NF1-related peripheral nerve sheath tumors called plexiform neurofibromas (PNs). AZD 6244 102-113 neurofibromin 1 Homo sapiens 165-168 32108293-0 2020 Selumetinib for plexiform neurofibromas in neurofibromatosis type 1: a single-institution experience. AZD 6244 0-11 neurofibromin 1 Homo sapiens 43-67 32108293-6 2020 Herein, we describe a single institutional experience with selumetinib for inoperable PN in NF-1. AZD 6244 59-70 neurofibromin 1 Homo sapiens 92-96 32108293-7 2020 METHODS: Case series study of demographics, clinical, baseline characteristics, treatment effect, and follow-up of consecutive genetically confirmed NF1 patients with inoperable PN associated with significant or potential significant morbidity treated with selumetinib (April 2018 to April 2019). AZD 6244 257-268 neurofibromin 1 Homo sapiens 149-152 31151904-0 2019 Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial. AZD 6244 0-11 neurofibromin 1 Homo sapiens 57-81 31151904-22 2019 INTERPRETATION: Selumetinib is active in recurrent, refractory, or progressive pilocytic astrocytoma harbouring common BRAF aberrations and NF1-associated paediatric low-grade glioma. AZD 6244 16-27 neurofibromin 1 Homo sapiens 140-143 31151904-23 2019 These results show that selumetinib could be an alternative to standard chemotherapy for these subgroups of patients, and have directly led to the development of two Children"s Oncology Group phase 3 studies comparing standard chemotherapy to selumetinib in patients with newly diagnosed paediatric low-grade glioma both with and without NF1. AZD 6244 24-35 neurofibromin 1 Homo sapiens 338-341