agerafenib

inhibitor of RAF family kinases; structure in first source

Also Known As:

1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)urea; 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)urea hydrochloride; CEP-32496; RXDX-105

Networked: 10 relevant articles (1 outcomes, 4 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Experts

1.	Drilon, Alexander: 3 articles (12/2020 - 06/2017)
2.	Liu, Stephen V: 2 articles (01/2022 - 01/2019)
3.	Hayashi, Takuo: 2 articles (12/2020 - 06/2017)
4.	Ladanyi, Marc: 2 articles (12/2020 - 06/2017)
5.	Smith, Roger S: 2 articles (12/2020 - 06/2017)
6.	Somwar, Romel: 2 articles (12/2020 - 06/2017)
7.	Oliver, Jennifer W: 2 articles (01/2019 - 06/2017)
8.	Patel, Rupal: 2 articles (01/2019 - 06/2017)
9.	Fujinaga, Masayuki: 2 articles (01/2018 - 08/2014)
10.	Xie, Lin: 2 articles (01/2018 - 08/2014)

Related Diseases

1.	Neuroblastoma 10/29/2019 - "Our results demonstrate that RXDX-105 shows promise as a novel therapeutic agent for children with high-risk and relapsed neuroblastoma." 10/29/2019 - "The multikinase inhibitor RXDX-105 is effective against neuroblastoma in vitro and in vivo." 10/29/2019 - "We found that treatment of neuroblastoma cells with RXDX-105 resulted in a significant decrease in cell viability and proliferation in vitro and in tumor growth and tumor vascularity in vivo. " 10/01/2019 - "Small molecule inhibitor agerafenib effectively suppresses neuroblastoma tumor growth in mouse models via inhibiting ERK MAPK signaling." 10/29/2019 - "RXDX-105 also showed enhanced efficacy in combination with 13-cis-retinoic acid, which is currently a component of maintenance therapy for children with high-risk neuroblastoma. "
2.	Neoplasms (Cancer) 06/15/2017 - ": These data support the inclusion of patients bearing RET alterations in ongoing and future molecularly enriched clinical trials to explore RXDX-105 efficacy across a variety of tumor types. " 06/15/2017 - " design: The RET-inhibitory activity of RXDX-105 was assessed by biochemical and cellular assays, followed by in vivo tumor growth inhibition studies in cell line- and patient-derived xenograft models. " 10/01/2019 - "More importantly, agerafenib exhibited a favorable toxicity profile, potently suppressed tumor growth, and prolonged survival in NB mouse models. " 01/01/2019 - "SIGNIFICANCE: Although KIF5B-RET is the most common RET fusion in NSCLCs, RET inhibition with RXDX-105 resulted in responses only in non-KIF5B-RET-containing cancers. " 06/15/2017 - "Antitumor Activity of RXDX-105 in Multiple Cancer Types with RET Rearrangements or Mutations."
3.	Sarcoma (Soft Tissue Sarcoma) 02/09/2012 - "Identification of 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)urea hydrochloride (CEP-32496), a highly potent and orally efficacious inhibitor of V-RAF murine sarcoma viral oncogene homologue B1 (BRAF) V600E." 01/01/2018 - "CEP-32496, also known as RXDX-105 or Agerafenib, is a new orally active inhibitor for the mutated v-raf murine sarcoma viral oncogene homolog B1 (BRAFV600E), which has attracted considerable attention in clinical trials for the treatment of human cancers. "
4.	Melanoma (Melanoma, Malignant) 01/01/2018 - "[11C]CEP-32496 showed high binding affinity for BRAFV600E-positive A375 melanoma cells and densely accumulated in the respective tissue sections; this could be blocked by the BRAFV600E selective antagonist sorafenib and by unlabeled CEP-32496. " 04/01/2012 - "CEP-32496 is a potent BRAF inhibitor in an in vitro binding assay for mutated BRAF(V600E) (K(d) BRAF(V600E) = 14 nmol/L) and in a mitogen-activated protein (MAP)/extracellular signal-regulated (ER) kinase (MEK) phosphorylation (pMEK) inhibition assay in human melanoma (A375) and colorectal cancer (Colo-205) cell lines (IC(50) = 78 and 60 nmol/L). "
5.	Lung Neoplasms (Lung Cancer) 06/15/2017 - "Additionally, a patient with advanced RET-rearranged lung cancer had a rapid and sustained response to RXDX-105 in both intracranial and extracranial disease.Conclusions" 12/14/2020 - "Moreover, cabozantinib was effective at reducing growth of a lung cancer PDX that was not responsive to RXDX-105. " 12/14/2020 - "Multi-kinase RET inhibitors, such as cabozantinib and RXDX-105, are active in lung cancer patients with RET fusions; however, the overall response rates to these two drugs are unsatisfactory compared to other targeted therapy paradigms. "

Related Drugs and Biologics

1.	agerafenib
2.	Phosphotransferases (Kinase)
3.	Protein Serine-Threonine Kinases (Protein-Serine-Threonine Kinase)
4.	MAP Kinase Kinase Kinases (MAP Kinase Kinase Kinase)
5.	Mitogen-Activated Protein Kinase Kinases (MEKs)
6.	Isotretinoin (Accutane)
7.	Proteins (Proteins, Gene)
8.	Mitogens
9.	Sorafenib (BAY 43-9006)
10.	cabozantinib

Related Therapies and Procedures

1.	Therapeutics