Safety assessment of metarrestin in dogs: A clinical candidate targeting a subnuclear structure unique to metastatic cancer cells.
Administration, Oral
Animals
Antineoplastic Agents
/ administration & dosage
Dogs
Drug Evaluation, Preclinical
ERG1 Potassium Channel
/ genetics
Female
HEK293 Cells
Humans
Male
No-Observed-Adverse-Effect Level
Pancreatic Neoplasms
/ drug therapy
Pyrimidines
/ administration & dosage
Pyrroles
/ administration & dosage
Metarrestin
Metastatic Cancer
Pancreatic cancer
Perinucleolar compartment
Preclinical toxicity
Safety Assessment
Safetypharmacology
Toxicokinetics
Journal
Regulatory toxicology and pharmacology : RTP
ISSN: 1096-0295
Titre abrégé: Regul Toxicol Pharmacol
Pays: Netherlands
ID NLM: 8214983
Informations de publication
Date de publication:
Oct 2020
Oct 2020
Historique:
received:
14
02
2020
revised:
09
05
2020
accepted:
16
06
2020
pubmed:
4
7
2020
medline:
10
4
2021
entrez:
4
7
2020
Statut:
ppublish
Résumé
Pancreatic cancer is a leading cause of cancer-related deaths in the U.S. Ninety percent of patients with stage IV pancreatic cancer die within one year of diagnosis due to complications of metastasis. A metastatic potential of cancer cells has been shown to be closely associated with formation of perinucleolar compartment (PNC). Metarrestin, a first-in-class PNC inhibitor, was evaluated for its toxicity, toxicokinetics, and safety pharmacology in beagle dogs following every other day oral (capsule) administration for 28 days to support its introduction into clinical trials. The study consisted of four dose groups: vehicle; 0.25, 0.75 and 1.50 mg/kg/dose. Metarrestin reached its maximum concentration in blood at 3 h (overall median T
Identifiants
pubmed: 32619635
pii: S0273-2300(20)30142-2
doi: 10.1016/j.yrtph.2020.104716
pmc: PMC8378239
mid: NIHMS1612441
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
ERG1 Potassium Channel
0
KCNH2 protein, human
0
Pyrimidines
0
Pyrroles
0
metarrestin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
104716Subventions
Organisme : CCR NIH HHS
ID : HHSN261200800001C
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA BC011267
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
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