Revefenacin trihydrate

Details

Stereochemistry	ACHIRAL
Molecular Formula	C35H43N5O4.3H2O
Molecular Weight	651.7929
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.O.O.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=GODDLKSFFJPOKV-UHFFFAOYSA-N

InChI=1S/C35H43N5O4.3H2O/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);3*1H2

HIDE SMILES / InChI

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C35H43N5O4
Molecular Weight	597.747
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 160 Target ID: CHEMBL245 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000PharmR.pdf	Antagonist 2849	0.39 nM [Kd]
Muscarinic acetylcholine receptor M1 168 Target ID: CHEMBL216 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000PharmR.pdf	Antagonist 2849	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 2849	0.61 nM [Kd]
Muscarinic acetylcholine receptor M4 87 Target ID: CHEMBL317 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000PharmR.pdf	Antagonist 2849	0.46 nM [Kd]
Muscarinic acetylcholine receptor M5 63 Target ID: CHEMBL277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000PharmR.pdf	Antagonist 2849	4.2 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic obstructive pulmonary disease 175 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210598s000lbl.pdf	Primary		Approved 8583	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 2018

C_max

Value	Dose	Analyte	Population
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
0.577 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
0.178 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
0.948 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
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
0.0742 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
0.105 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
0.178 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

AUC

Value	Dose	Analyte	Population
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
0.443 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
0.299 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
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
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
0.117 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
0.0702 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
0.259 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

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

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 substrate 1946	inhibitor 2438	inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2B6 926 CYP2C8 1057 CYP2C19 2057 OATP1B1 1079 OATP1B3 961 OAT1 725 OAT3 747 OCT2 779 BCRP 910	CYP3A 220 CYP3A5 446 OATP1B1 503 OATP1B3 435 OAT1 395 OAT2 125 OAT3 391 P-gp 2052 BCRP 697	CYP1A2 832 CYP2B6 669 CYP3A4/5 133

Drug as perpetrator

Target	Modality	Activity	Metabolite
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	no
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	no	THRX-195518 2
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=12 Page: 12.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=51 Page: 51.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	no	THRX-195518 2
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=12 Page: 12.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=51 Page: 51.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	no	THRX-195518 2
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=15 Page: 15.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	no	THRX-195518 2
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=51 Page: 51.0	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	no	THRX-195518 2
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=15 Page: 15.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	no	THRX-195518 2
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=51 Page: 51.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	no	THRX-195518 2
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=15 Page: 15.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	no	THRX-195518 2
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=53 Page: 53.0	no
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=53 Page: 53.0	no	THRX-195518 2
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=53 Page: 53.0	no
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=53 Page: 53.0	no	THRX-195518 2
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=53 Page: 53.0	no
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=53 Page: 53.0	no	THRX-195518 2
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=53 Page: 53.0	no
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=53 Page: 53.0	no	THRX-195518 2
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=53 Page: 53.0	no
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=53 Page: 53.0	no	THRX-195518 2
CYP3A4/5 357	inducer 1966 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 395	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
OAT2 125	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
OAT3 391	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=12 Page: 12.0	yes
CYP3A 220	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=27 Page: 27.0	yes
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=27 Page: 27.0	yes
CYP3A5 446	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=27 Page: 27.0	yes
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	yes
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	yes	THRX-195518 2
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	yes
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=56 Page: 56.0	yes	THRX-195518 2
BCRP 697	substrate 4014 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 2052	substrate 4014 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 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=33 Page: 33.0
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210598Orig1s000ClinPharmR.pdf#page=33 Page: 33.0		THRX-195518 2

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
BioChemPartner	BCP15793	http://www.biochempartner.com/864750-70-9-BCP15793
BOC Sciences	864750-70-9	https://www.bocsci.com/revefenacin-cas-864750-70-9-item-470939.html
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
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
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

PubMed

Title	Date	PubMed

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.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 15:12:59 GMT 2025` Edited by `admin` on `Wed Apr 02 15:12:59 GMT 2025`
Record UNII	CB9J2CKN88
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

1-(2-(4-((4-Carbamoylpiperidin-1-yl)methyl)-N-methylbenzamido)ethyl)piperidin-4-yl [1,1?-biphenyl]-2-ylcarbamate trihydrate

Preferred Name

English

Revefenacin trihydrate

Common Name

English

Code System Code Type Description

PUBCHEM

171390019

Created by admin on Wed Apr 02 15:12:59 GMT 2025 , Edited by admin on Wed Apr 02 15:12:59 GMT 2025

PRIMARY

FDA UNII

CB9J2CKN88

Created by admin on Wed Apr 02 15:12:59 GMT 2025 , Edited by admin on Wed Apr 02 15:12:59 GMT 2025

PRIMARY

Related Record Type Details


					G2AE2VE07O

REVEFENACIN

ANHYDROUS->SOLVATE

Amount:


					G2AE2VE07O

REVEFENACIN

PARENT -> SALT/SOLVATE

Amount:

Related Record Type Details


					G2AE2VE07O

REVEFENACIN

ACTIVE MOIETY

Amount:

Details

SMILES

InChI

DescriptionSources: 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

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Launch Date

Cmax

AUC

T1/2

Funbound

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

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

C_max

T_1/2

F_unbound

Drug as perpetrator