ACOTIAMIDE HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H30N4O5S.ClH.3H2O
Molecular Weight	541.058
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.O.O.Cl.COC1=CC(O)=C(C=C1OC)C(=O)NC2=NC(=CS2)C(=O)NCCN(C(C)C)C(C)C

InChI

InChIKey=NPTDXIXCQCFGKC-UHFFFAOYSA-N

InChI=1S/C21H30N4O5S.ClH.3H2O/c1-12(2)25(13(3)4)8-7-22-20(28)15-11-31-21(23-15)24-19(27)14-9-17(29-5)18(30-6)10-16(14)26;;;;/h9-13,26H,7-8H2,1-6H3,(H,22,28)(H,23,24,27);1H;3*1H2

HIDE SMILES / InChI

Molecular Formula	C21H30N4O5S
Molecular Weight	450.552
Charge	0
Count

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

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	ClH
Molecular Weight	36.461
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23881665
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/21123674 | https://www.ncbi.nlm.nih.gov/pubmed/10871292 | https://www.astellas.com/en/corporate/news/pdf/130605_1_Eg.pdf

Acotiamide (Acofide(®)), an oral first-in-class prokinetic drug, is under global development by Zeria Pharmaceutical Co. Ltd and Astellas Pharma Inc. for the treatment of patients with functional dyspepsia. The drug modulates upper gastrointestinal motility to alleviate abdominal symptoms resulting from hypomotility and delayed gastric emptying. It exerts its activity in the stomach via muscarinic receptor inhibition, resulting in enhanced acetylcholine release and inhibition of acetylcholinesterase activity. Acofide® is launched in Japan for treating functional dyspepsia.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Acetylcholinesterase 209 Target ID: CHEMBL220 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21123674	Inhibitor 8504	3.0 µM [IC50]
Muscarinic acetylcholine receptor M1 168 Target ID: CHEMBL276 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10871292	Antagonist 2849
Muscarinic acetylcholine receptor M2 121 Target ID: CHEMBL211 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10871292	Antagonist 2849

Conditions

Condition	Modality	Targets	Highest Phase	Product
Functional dyspepsia 12 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23881665	Primary		Approved 8583	ACOFIDE Approved Use Acofide (Acotiamide hydrochloride hydrate) improves gastrointestinal motility and promotes excretion of stomach contents by inhibiting acetylcholinesterase activities. It is usually used for the treatment of postprandial fullness, upper abdominal bloating, and early satiation due to functional dyspepsia. Launch Date 2013

C_max

Value	Dose	Analyte	Population
25.71 ng/mL EXPERIMENT https://journals.innovareacademics.in/index.php/ijpps/article/view/38410	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ACOTIAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
200 ng/mL OTHER GOV'T https://www.pmda.go.jp/files/000153467.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	ACOTIAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
168.2 ng/mL OTHER GOV'T https://www.pmda.go.jp/files/000153467.pdf	300 mg 3 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ACOTIAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
451.59 ng/mL OTHER GOV'T https://www.pmda.go.jp/files/000153467.pdf	900 mg 3 times / day multiple, oral dose: 900 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ACOTIAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
511.75 ng × h/mL EXPERIMENT https://journals.innovareacademics.in/index.php/ijpps/article/view/38410	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ACOTIAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
537.2 ng × h/mL OTHER GOV'T https://www.pmda.go.jp/files/000153467.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	ACOTIAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1215 ng × h/mL OTHER GOV'T https://www.pmda.go.jp/files/000153467.pdf	300 mg 3 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ACOTIAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1659.57 ng × h/mL OTHER GOV'T https://www.pmda.go.jp/files/000153467.pdf	900 mg 3 times / day multiple, oral dose: 900 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ACOTIAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
23.49 h EXPERIMENT https://journals.innovareacademics.in/index.php/ijpps/article/view/38410	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ACOTIAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
8.99 h OTHER GOV'T https://www.pmda.go.jp/files/000153467.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	ACOTIAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
11.25 h OTHER GOV'T https://www.pmda.go.jp/files/000153467.pdf	300 mg 3 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ACOTIAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Analyte	Population
14.92% OTHER GOV'T https://www.pmda.go.jp/files/000153467.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	ACOTIAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
14.92% OTHER GOV'T https://www.pmda.go.jp/files/000153467.pdf	300 mg 3 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ACOTIAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
14.92% OTHER GOV'T https://www.pmda.go.jp/files/000153467.pdf	900 mg 3 times / day multiple, oral dose: 900 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ACOTIAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21934307/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21934307/	Other AEs: Constipation, Diarrhea... Other AEs: Constipation (2.2%) Diarrhea (2.2%) ALT increased (1.5%) Gamma-glutamyltransferase increased (1%) Sources: https://pubmed.ncbi.nlm.nih.gov/21934307/
100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/29315999/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/29315999/	Disc. AE: Nausea, Dyspepsia... AEs leading to discontinuation/dose reduction: Nausea (1.4%) Dyspepsia (0.97%) Constipation (0.48%) Eructation (0.48%) Gastrointestinal sounds abnormal (0.48%) Reflux gastritis (0.48%) Appetite decreased NOS (0.48%) Dysgeusia (0.48%) Sources: https://pubmed.ncbi.nlm.nih.gov/29315999/

AEs

AE	Significance	Dose	Population
Gamma-glutamyltransferase increased	1%	100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21934307/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21934307/
ALT increased	1.5%	100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21934307/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21934307/
Constipation	2.2%	100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21934307/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21934307/
Diarrhea	2.2%	100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21934307/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21934307/
Appetite decreased NOS	0.48% Disc. AE	100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/29315999/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/29315999/
Constipation	0.48% Disc. AE	100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/29315999/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/29315999/
Dysgeusia	0.48% Disc. AE	100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/29315999/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/29315999/
Eructation	0.48% Disc. AE	100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/29315999/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/29315999/
Gastrointestinal sounds abnormal	0.48% Disc. AE	100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/29315999/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/29315999/
Reflux gastritis	0.48% Disc. AE	100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/29315999/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/29315999/
Dyspepsia	0.97% Disc. AE	100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/29315999/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/29315999/
Nausea	1.4% Disc. AE	100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/29315999/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/29315999/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 substrate 1946	substrate 1193 inhibitor 2438	substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2B6 926 CYP2A6 879 CYP1A1/2 3 P-gp 1741 CYP2E1 1060	CYP2C19 1119 CYP2B6 776 UGT1A4 399 UGT1A8 323 P-gp 2052 UGT1A9 423 CYP1A1 389 CYP2C8 810 UGT1A1 479 UGT1A3 470 UGT1A6 343 CYP2A6 626 CYP2C18 149 CYP1A2 1197 UGT1A10 331 UGT2B7 456 UGT2B15 236 CYP2E1 729 CYP3A5 446 CYP4A11 137

Drug as perpetrator

Target	Modality	Activity
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/15306208/	no [Ki 1030.8 uM]
CYP2A6 911	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/15306208/	no [Ki 140.5 uM]
CYP1A1/2 3	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/15306208/	no [Ki 225.5 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/15306208/	no [Ki 2624.7 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/15306208/	no [Ki >10000 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/15306208/	no
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/15306208/	weak

Drug as victim

Target	Modality	Activity
UGT1A8 323	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15306208/	major [Km 1430 uM]
UGT1A9 423	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15306208/	major [Km 43.13 uM]
CYP2C8 810	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2013/P201300021/38007700_22500AMX00868000_A100_1.pdf Page: 30.0	major
CYP1A1 389	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2013/P201300021/38007700_22500AMX00868000_A100_1.pdf Page: 30.0	minor
CYP3A4 1946	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2013/P201300021/38007700_22500AMX00868000_A100_1.pdf Page: 30.0	minor
CYP1A2 1197	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2013/P201300021/38007700_22500AMX00868000_A100_1.pdf Page: 30.0	no
CYP2A6 626	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2013/P201300021/38007700_22500AMX00868000_A100_1.pdf Page: 30.0	no
CYP2B6 776	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2013/P201300021/38007700_22500AMX00868000_A100_1.pdf Page: 30.0	no
CYP2E1 729	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2013/P201300021/38007700_22500AMX00868000_A100_1.pdf Page: 30.0	no
P-gp 2052	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2013/P201300021/38007700_22500AMX00868000_A100_1.pdf Page: 23.0	weak [Km 697 uM]
CYP2C18 149	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2013/P201300021/38007700_22500AMX00868000_A100_1.pdf Page: 30.0	weak
CYP2C19 1119	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2013/P201300021/38007700_22500AMX00868000_A100_1.pdf Page: 30.0	weak
CYP2C9 1193	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2013/P201300021/38007700_22500AMX00868000_A100_1.pdf Page: 30.0	weak
CYP2D6 1388	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2013/P201300021/38007700_22500AMX00868000_A100_1.pdf Page: 30.0	weak
CYP3A5 446	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2013/P201300021/38007700_22500AMX00868000_A100_1.pdf Page: 30.0	weak
CYP4A11 137	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2013/P201300021/38007700_22500AMX00868000_A100_1.pdf Page: 30.0	weak
UGT1A1 479	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15306208/	weak
UGT1A10 331	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15306208/	weak
UGT1A3 470	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15306208/	weak
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15306208/	weak
UGT1A6 343	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15306208/	weak
UGT2B15 236	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15306208/	weak
UGT2B7 456	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15306208/	weak

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/15306208/

PubMed

Title	Date	PubMed
Acotiamide (Z-338) as a possible candidate for the treatment of functional dyspepsia.	2010-06	20553562
Clinical trial: dose-dependent therapeutic efficacy of acotiamide hydrochloride (Z-338) in patients with functional dyspepsia - 100 mg t.i.d. is an optimal dosage.	2010-06	20059698
A dose-ranging, placebo-controlled, pilot trial of Acotiamide in patients with functional dyspepsia.	2009-03	19254354
Prokinetics and fundic relaxants in upper functional GI disorders.	2008-12	18940266
[Functional and motor gastrointestinal disorders].	2008-10	19434861
Acotiamide hydrochloride (Z-338), a novel prokinetic agent, restores delayed gastric emptying and feeding inhibition induced by restraint stress in rats.	2008-09	18482254
Drug-drug interactions of Z-338, a novel gastroprokinetic agent, with terfenadine, comparison with cisapride, and involvement of UGT1A9 and 1A8 in the human metabolism of Z-338.	2004-08-23	15306208

Patents

Sample Use Guides

In Vivo Use Guide

In general, for adults, take 1 tablet (100mg of the active ingredient) at a time, 3 times a day before meals.

Route of Administration: Oral

In Vitro Use Guide

Acotiamide (0.3 and 1 uM) significantly enhanced the contraction of guinea pig gastric body strips induced by electrical field stimulation

Substance Class	Chemical Created by `admin` on `Mon Mar 31 21:25:13 GMT 2025` Edited by `admin` on `Mon Mar 31 21:25:13 GMT 2025`
Record UNII	NMW7447A9A
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ACOTIAMIDE HYDROCHLORIDE TRIHYDRATE

Preferred Name

English

ACOTIAMIDE HYDROCHLORIDE

Official Name

English

ACOTIAMIDE HYDROCHLORIDE TRIHYDRATE [MI]

Common Name

English

ACOTIAMIDE HYDROCHLORIDE HYDRATE [JAN]

Common Name

English

Z-338

Code

English

YM-443

Code

English

N-[2-[Bis(1-methylethyl)amino]ethyl]-2-[(2-hydroxy-4,5-dimethoxybenzoyl)amino]thiazole-4-carboxamide monohydrochloride trihydrate

Systematic Name

English

ACOTIAMIDE HYDROCHLORIDE HYDRATE

Common Name

English

ACOTIAMIDE HYDROCHLORIDE [USAN]

Common Name

English

4-THIAZOLECARBOXAMIDE, N-(2-(BIS(1-METHYLETHYL)AMINO)ETHYL)-2-((2-HYDROXY-4,5-DIMETHOXYBENZOYL)AMINO)-, MONOHYDROCHLORIDE, TRIHYDRATE

Common Name

English

YM443

Code

English

4-THIAZOLECARBOXAMIDE, N-(2-(BIS(1-METHYLETHYL)AMINO)ETHYL)-2-((2-HYDROXY-4,5-DIMETHOXYBENZOYL)AMINO)-, HYDROCHLORIDE, HYDRATE (1:1:3)

Systematic Name

English

Acotiamide hydrochloride trihydrate [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C267