General
Preferred name
REVEFENACIN
Synonyms
TD-4208 ()
GSK1160724 ()
TD-4208, GSK-1160724 ()
Yupelri ()
GSK-1160724 ()
P&D ID
PD058906
CAS
864750-70-9
Tags
available
drug
Approved by
FDA
First approval
2018
Drug Status
investigational
approved
Drug indication
Chronic obstructive pulmonary disease
Max Phase
Phase 4
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
TOXICITY Revefenacin does not produce the typical systemic effects associated with anticholinergic therapies.[A40025] In carcinogenic studies in animals, there was no evidence of tumorigenicity. As well, there was no evidence of mutagenicity in the Ames test nor genotoxicity in _in vitro_ mouse lymphoma assays and _in vivo_ rat bone marrow micronucleus assays. There is no effect in the fertility.[FDA label]; ; In overdose situations, the common signs and symptoms are nausea, vomiting, dizziness, lightheadedness, blurred vision, increased intraocular pressure, obstipation and difficulties in voiding.[FDA label]
PHARMACODYNAMICS Revefenacin has been reported to produce a sustained, long-acting bronchodilation with lower anti-muscarinic-related side effects. In clinical trials, revefenacin demonstrated to be of a long duration of action and low systemic exposure in patients with COPD. Also, it was reported that a dose of 88 mcg can produce a clinically effective bronchodilation measured by through forced expiratory volume in 1s and serial spirometric assessments.[A40027]; ; In placebo-controlled trials, revefenacin showed a decrease in the use of albuterol rescue inhalers and sustained increases in the peak expiratory flow rate that reached a steady state at a maximum in day 7. As well, there was a reported superior lung selectivity index when compared with other LABAs such as glycopyrronium and tiotropium which produced a decreased sialagogue effect.[A40025]
MOA Revefenacin is an inhaled bronchodilator muscarinic antagonist with a long-acting bronchodilation activity.[A40028] It has been shown to present a high affinity and behaved as a competitive antagonist of the five muscarinic cholinergic receptors. Studies have indicated that revefenacin dissociates significantly slower from the muscarinic receptor M3 (hM3) when compared to the receptor M2 (hM2) which indicates a kinetic selectivity for this subtype. This competitive antagonism produces a suppressive action of the acetylcholine-evoked calcium mobilization and contractile responses in the airway tissue.[A40029] Lastly, due to the duration of the bronchodilation, revefenacin is considered a long-acting muscarinic antagonist which allows it to be dosed once daily.[A40031]; ; This response is very important for the therapy of COPD as the main goal is the reduce the frequency and severity of exacerbations which are normally driven by the presence of elevated cholinergic bronchoconstrictor tone mediated by muscarinic receptors on parasympathetic ganglia and airway smooth muscle.[A40030] Hence, the activity of revefenacin produces a potent and long-lasting protection against the bronchoconstrictor response to acetylcholine or methacholine.[A40029]
INDICATION Revefenacin is indicated as an inhalation solution for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).[L4820]; ; COPD is a growing disease being the third leading cause of death in the US. This disease is characterized by not fully reversible airflow limitation.[L4821]
ROE After reaching maximum concentration, revefenacin concentrations decline in a biphasic manner.[A40025] This elimination kinetics is observed by a rapid declining plasma concentration followed by a slow apparent bi-exponential elimination. Renal elimination of revefenacin is limited and it presents a mean cumulative amount excreted in urine as the unchanged drug of < 0.2% of the administered dose.[A40028]; ; Following intravenous revefenacin administration, 54% of the dose is recovered in feces and 27% was recovered in urine which confirms a high hepatobiliary processing.[L4823]
DESCRIPTION Revefenacin (TD-4208) is a potent and long-acting muscarinic cholinergic receptor (mAChR) antagonist (LAMA) that has bronchodilatory effects , and which is approved for the management of chronic obstructive pulmonary disease (COPD). mAChR antagonists are the core agents used as first-line therapy for COPD. Revefenacin acts as a competitive antagonist at all 5 human mAChRs . (GtoPdb)
Compound Sets
18
AdooQ Bioactive Compound Library
A15986
Cayman Chemical Bioactives
36549
ChEMBL Approved Drugs
CHEMBL3833319
ChEMBL Drugs
CHEMBL3833319
Drug Repurposing Hub
DrugBank
DB11855
DrugBank Approved Drugs
DB11855
DrugCentral
5303
DrugCentral Approved Drugs
5303
DrugMAP
DMMP5SI
DrugMAP Approved Drugs
DMMP5SI
EU-OPENSCREEN Bioactive Compound Library
EOS100079
Guide to Pharmacology
10129
MedChem Express Bioactive Compound Library
HY-15851
NCATS Inxight Approved Drugs
G2AE2VE07O
ReFrame library
Selleckchem Bioactive Compound Library
revefenacin
TargetMol Bioactive Compound Library
T7392
External IDs
23
Properties
(calculated by RDKit )
Molecular Weight
597.33
Hydrogen Bond Acceptors
6
Hydrogen Bond Donors
2
Rotatable Bonds
10
Ring Count
5
Aromatic Ring Count
3
cLogP
4.84
TPSA
108.21
Fraction CSP3
0.4
Chiral centers
0.0
Largest ring
6.0
QED
0.35
Structural alerts
0
No structural alerts detected
Custom attributes
(extracted from source data)
Pathway
Neuroscience
GPCR/G protein
Neuronal Signaling
Target
mAChR
AChR
MOA
cholinergic receptor antagonist
Source data