REVEFENACIN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C35H43N5O4
Molecular Weight	597.747
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(CCN1CCC(CC1)OC(=O)NC2=CC=CC=C2C3=CC=CC=C3)C(=O)C4=CC=C(CN5CCC(CC5)C(N)=O)C=C4

InChI

InChIKey=FYDWDCIFZSGNBU-UHFFFAOYSA-N

InChI=1S/C35H43N5O4/c1-38(34(42)29-13-11-26(12-14-29)25-40-19-15-28(16-20-40)33(36)41)23-24-39-21-17-30(18-22-39)44-35(43)37-32-10-6-5-9-31(32)27-7-3-2-4-8-27/h2-14,28,30H,15-25H2,1H3,(H2,36,41)(H,37,43)

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210598s000lbl.pdf | https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000PharmR.pdf | https://www.ncbi.nlm.nih.gov/pubmed/30601616

Revefenacin (trade name Yupelri is a long-acting muscarinic antagonist developed by Mylan Ireland ltd for the treatment of chronic obstructive pulmonary disease (COPD). It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3 receptor at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo models, prevention of methacholine- and acetylcholine-induced bronchoconstrictive effects was dose-dependent and lasted longer than 24 hours.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Muscarinic acetylcholine receptor M3 159 Target ID: CHEMBL245 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000PharmR.pdf	Antagonist 2778	0.39 nM [Kd]
Muscarinic acetylcholine receptor M1 169 Target ID: CHEMBL216 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000PharmR.pdf	Antagonist 2778	1.0 nM [Kd]
Muscarinic acetylcholine receptor M2 121 Target ID: CHEMBL211 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000PharmR.pdf	Antagonist 2778	0.61 nM [Kd]
Muscarinic acetylcholine receptor M4 86 Target ID: CHEMBL317 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000PharmR.pdf	Antagonist 2778	0.46 nM [Kd]
Muscarinic acetylcholine receptor M5 62 Target ID: CHEMBL277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000PharmR.pdf	Antagonist 2778	4.2 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic obstructive pulmonary disease 174 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210598s000lbl.pdf	Primary		Approved 8429	YUPELRI Approved Use YUPELRI (revefenacin) inhalation solution is an anticholinergic indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Launch Date 1.53653766E12

C_max

Value	Dose	Analyte	Population
0.105 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	175 μg single, respiratory dose: 175 μg route of administration: Respiratory experiment type: SINGLE co-administered:	REVEFENACIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.114 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	175 μg 1 times / day steady-state, respiratory dose: 175 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered:	REVEFENACIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.309 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	175 μg single, respiratory dose: 175 μg route of administration: Respiratory experiment type: SINGLE co-administered:	REVEFENACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.577 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	700 μg 1 times / day steady-state, respiratory dose: 700 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered:	REVEFENACIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.0742 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	175 μg single, respiratory dose: 175 μg route of administration: Respiratory experiment type: SINGLE co-administered:	THRX-195518 plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.178 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	175 μg 1 times / day steady-state, respiratory dose: 175 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered:	THRX-195518 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.178 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	175 μg single, respiratory dose: 175 μg route of administration: Respiratory experiment type: SINGLE co-administered:	THRX-195518 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.948 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	700 μg 1 times / day steady-state, respiratory dose: 700 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered:	THRX-195518 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
0.0702 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	175 μg single, respiratory dose: 175 μg route of administration: Respiratory experiment type: SINGLE co-administered:	REVEFENACIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.092 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	175 μg 1 times / day steady-state, respiratory dose: 175 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered:	REVEFENACIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.161 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	175 μg single, respiratory dose: 175 μg route of administration: Respiratory experiment type: SINGLE co-administered:	REVEFENACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.443 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	700 μg 1 times / day steady-state, respiratory dose: 700 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered:	REVEFENACIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.117 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	175 μg single, respiratory dose: 175 μg route of administration: Respiratory experiment type: SINGLE co-administered:	THRX-195518 plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.299 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	175 μg 1 times / day steady-state, respiratory dose: 175 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered:	THRX-195518 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.259 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	175 μg single, respiratory dose: 175 μg route of administration: Respiratory experiment type: SINGLE co-administered:	THRX-195518 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.48 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	700 μg 1 times / day steady-state, respiratory dose: 700 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered:	THRX-195518 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
23 h OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	700 μg 1 times / day steady-state, respiratory dose: 700 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered:	REVEFENACIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
23.5 h OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	175 μg 1 times / day steady-state, respiratory dose: 175 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered:	THRX-195518 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
22.3 h OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	700 μg 1 times / day steady-state, respiratory dose: 700 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered:	THRX-195518 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Analyte	Population
29% OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	175 μg 1 times / day steady-state, respiratory dose: 175 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered:	REVEFENACIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
29% OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	700 μg 1 times / day steady-state, respiratory dose: 700 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered:	REVEFENACIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
42% OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	175 μg 1 times / day steady-state, respiratory dose: 175 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered:	THRX-195518 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
42% OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf	700 μg 1 times / day steady-state, respiratory dose: 700 μg route of administration: Respiratory experiment type: STEADY-STATE co-administered:	THRX-195518 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
175 ug 1 times / day steady, respiratory Recommended Dose: 175 ug, 1 times / day Route: respiratory Route: steady Dose: 175 ug, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210598s000lbl.pdf	unhealthy, 64 years (range: 41 - 88 years) n = 418 Health Status: unhealthy Condition: chronic obstructive pulmonary disease Age Group: 64 years (range: 41 - 88 years) Population Size: 418 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210598s000lbl.pdf	Other AEs: Cough, Nasopharyngitis... Other AEs: Cough (4%) Nasopharyngitis (4%) Upper respiratory tract infection (3%) Headache (4%) Back pain (2%) Hypertension (1-2) Dizziness (1-2) Oropharyngeal pain (1-2) Bronchitis (1-2) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210598s000lbl.pdf
175 ug 1 times / day steady, respiratory Dose: 175 ug, 1 times / day Route: respiratory Route: steady Dose: 175 ug, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000MedR.pdf	unhealthy n = 427 Health Status: unhealthy Condition: COPD Population Size: 427 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000MedR.pdf	Disc. AE: Hypertension... AEs leading to discontinuation/dose reduction: Hypertension (0.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000MedR.pdf
175 ug 1 times / day steady, respiratory Dose: 175 ug, 1 times / day Route: respiratory Route: steady Dose: 175 ug, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000MedR.pdf Page: p. 72	unhealthy n = 427 Health Status: unhealthy Condition: COPD Population Size: 427 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000MedR.pdf Page: p. 72	Disc. AE: Cough, Bronchiectasis... AEs leading to discontinuation/dose reduction: Cough (0.5%) Bronchiectasis (0.2%) Bronchospasm paradoxical (0.2%) Hypoxia (0.2%) Bronchitis (0.5%) Pneumonia (0.5%) Gastroenteritis (0.2%) Upper respiratory tract infection (0.2%) Atypical pneumonia (0.2%) Pneumonia parainfluenzae viral (0.2%) Urinary tract infection (0.2%) Abdominal distension (0.2%) Dry mouth (0.2%) Oral pain (0.2%) Headache (0.2%) Acute myocardial infarction (0.2%) Colon cancer (0.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000MedR.pdf Page: p. 72

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 substrate 1737	inhibitor 1767	inhibitor 1852 substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2B6 810 CYP2C8 911 CYP2C19 1478 OATP1B1 788 OATP1B3 706 OAT1 599 OAT3 642 OCT2 647 BCRP 699	CYP3A 191 CYP3A5 395 OATP1B1 406 OATP1B3 350 OAT1 326 OAT2 115 OAT3 339 P-gp 1537 BCRP 561	CYP1A2 701 CYP2B6 547 CYP3A4/5 124

Drug as perpetrator

Target	Modality	Activity	Metabolite
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	no
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	no	THRX-195518 1
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=12 Page: 12.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=51 Page: 51.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	no	THRX-195518 1
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=12 Page: 12.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=51 Page: 51.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	no	THRX-195518 1
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=15 Page: 15.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	no	THRX-195518 1
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=51 Page: 51.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	no	THRX-195518 1
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=15 Page: 15.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	no	THRX-195518 1
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=51 Page: 51.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	no	THRX-195518 1
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=15 Page: 15.0	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	no	THRX-195518 1
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=53 Page: 53.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=53 Page: 53.0	no	THRX-195518 1
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=53 Page: 53.0	no
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=53 Page: 53.0	no	THRX-195518 1
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=53 Page: 53.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=53 Page: 53.0	no	THRX-195518 1
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=53 Page: 53.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=53 Page: 53.0	no	THRX-195518 1
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=53 Page: 53.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=53 Page: 53.0	no	THRX-195518 1
CYP3A4/5 335	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=12 Page: 12.0	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
OAT2 115	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=12 Page: 12.0	yes
CYP3A 191	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=27 Page: 27.0	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=27 Page: 27.0	yes
CYP3A5 395	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=27 Page: 27.0	yes
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	yes
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	yes	THRX-195518 1
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	yes
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	yes	THRX-195518 1
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	yes		unlikely Comment: Available information from DDI studies conducted for digoxin (P-gp substrates) suggest that the increase in exposure (AUC and Cmax) in the presence of P-gp inhibitors is expected to be generally less than 2-fold (Refer to prescribing information for digoxin). The available clinical data (total N= 115) at 350 µg dose (2 times above 175 µg) from studies 0091 and 0117 suggest that a 2-fold exposure increase was generally safe. Considering these factors, the expected increase in the systemic of revefenacin with P-gp or BCRP inhibition is unlikely to have a clinically meaningful impact on safety of the proposed dose. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	yes		unlikely Comment: Available information from DDI studies conducted for digoxin (P-gp substrates) suggest that the increase in exposure (AUC and Cmax) in the presence of P-gp inhibitors is expected to be generally less than 2-fold (Refer to prescribing information for digoxin). The available clinical data (total N= 115) at 350 µg dose (2 times above 175 µg) from studies 0091 and 0117 suggest that a 2-fold exposure increase was generally safe. Considering these factors, the expected increase in the systemic of revefenacin with P-gp or BCRP inhibition is unlikely to have a clinically meaningful impact on safety of the proposed dose. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=33 Page: 33.0
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=33 Page: 33.0		THRX-195518 1

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY445243	https://www.001chemical.com/chem/864750-70-9
AA Blocks	AA00H1HI	https://www.aablocks.com/goods/Goods/detail?id=AA00H1HI
AbMole Bioscience	M6127	http://www.abmole.com/products/cpdd1221.html
Achemtek	0102-032475	http://www.achemtek.com/864750-70-9-2
Acorn PharmaTech	ACN-051241	http://www.acornpharmatech.com/
Adooq BioScience	A15986	https://www.adooq.com/revefenacin.html
Angel Pharmatech	AG-12148	http://www.angelpharmatech.com/864750-70-9.html
Ark Pharma Scientific Limited	A-1555	http://www.arkpharmtech.com/product/33506.html
BOC Sciences	864750-70-9	https://www.bocsci.com/revefenacin-cas-864750-70-9-item-470939.html
BioChemPartner	BCP15793	http://www.biochempartner.com/864750-70-9-BCP15793
Chem Scene	CS-7743	http://www.chemscene.com/864750-70-9.html
Chemspace	CSSB00161189496	https://chem-space.com/CSSB00161189496
DC Chemicals	DC8813	http://www.dcchemicals.com/product_show-TD_4208.html
Excenen	EX-A1722	http://www.excenen.com/searchresultlist.php?id=864750-70-9
Hairui	ACSA02511	http://www.hairuichem.com/en/product/864750-70-9.html
Lab Network	LN01344948	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01344948
MedChem Express	HY-15851	https://www.medchemexpress.com/Revefenacin.html
Molcore	MC445243	https://www.molcore.com/product/864750-70-9
Smolecule	S541280	http://www.smolecule.com/products/s541280
Smolecule	S785590	https://www.smolecule.com/products/s785590
Synblock Inc	SB17262	http://www.synblock.com/product/864750-70-9.html
THE BioTek	bt-280247	https://www.thebiotek.com/product/inhibitors/bt-280247
eNovation Chemicals	D589724	https://www.enovationchem.com/ProductDetails.asp?ProductID=D589724
eNovation Chemicals	D676393	https://www.enovationchem.com/ProductDetails.asp?ProductID=D676393
eNovation Chemicals	Y0975758	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0975758

PubMed

Title	Date	PubMed
Revefenacin.	2006	30601616

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose of YUPELRI (revefenacin) inhalation solution is one 175 mkg unit-dose vial administered once daily by nebulizer using a mouthpiece.

Route of Administration: Respiratory

In Vitro Use Guide

CHO-K1 cell membrane fractions expressing human recombinant M2 or M3 mAChRs were incubated with [3H]revefenacin (18.5 Ci/mmol), [3H]glycopyrrolate (70 Ci_mmol_1), for 1 hours at 37°C or [3H]tiotropium (70 Ci/mmol) for 4 hours at 37°C. Nonspecific binding was defined in the presence of 10 mkmol/L atropine.

Name

Type

Language

REVEFENACIN

Official Name

English

1-(2-(4-((4-CARBAMOYLPIPERIDIN-1-YL)METHYL)-N-METHYLBENZAMIDO)ETHYL)PIPERIDIN-4-YL N-((1,1'-BIPHENYL)-2-YL)CARBAMATE

Systematic Name

English

GSK-1160724

Code

English

TD-4208

Code

English

GSK1160724

Code

English

REVEFENACIN [MI]

Common Name

English

YUPELRI

Brand Name

English

REVEFENACIN [ORANGE BOOK]

Common Name

English

CARBAMIC ACID, N-(1,1'-BIPHENYL)-2-YL-, 1-(2-((4-((4-(AMINOCARBONYL)-1-PIPERIDINYL)METHYL)BENZOYL)METHYLAMINO)ETHYL)-4-PIPERIDINYL ESTER

Systematic Name

English

REVEFENACIN [USAN]

Common Name

English

Revefenacin [WHO-DD]

Common Name

English

revefenacin [INN]

Common Name

English

BIPHENYL-2-YLCARBAMIC ACID, 1-(2-((4-(4-CARBAMOYLPIPERIDIN-1-YLMETHYL)BENZOYL)METHYLAMINO)ETHYL)PIPERIDIN-4-YL ESTER

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29704