MOTESANIB

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H23N5O
Molecular Weight	373.4509
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1(C)CNC2=CC(NC(=O)C3=CC=CN=C3NCC4=CC=NC=C4)=CC=C12

InChI

InChIKey=RAHBGWKEPAQNFF-UHFFFAOYSA-N

InChI=1S/C22H23N5O/c1-22(2)14-26-19-12-16(5-6-18(19)22)27-21(28)17-4-3-9-24-20(17)25-13-15-7-10-23-11-8-15/h3-12,26H,13-14H2,1-2H3,(H,24,25)(H,27,28)

HIDE SMILES / InChI

Molecular Formula	C22H23N5O
Molecular Weight	373.4509
Charge	0
Count

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

Description
Sources: http://adisinsight.springer.com/drugs/800011016
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16951187

Motesanib (AMG 706), a novel nicotinamide, was identified as a potent, orally bioavailable inhibitor of the VEGFR1/Flt1, VEGFR2/kinase domain receptor/Flk-1, VEGFR3/Flt4 and Kit receptors. Motesanib was expected to reduce vascular permeability and blood flow in human tumours. A phase III trial of motesanib in combination with paclitaxel and carboplatin in non-squamous NSCLC has been terminated by Takeda and subsequently the development was discontinued. Motesanib has also been investigated up to phase II in breast, thyroid, colorectal and gastrointestinal stromal tumours. However, development has been discontinued in these indications.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Vascular endothelial growth factor receptor 1 44 Target ID: CHEMBL1868 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=16951187	Inhibitor 8504	2.0 nM [IC50]
Vascular endothelial growth factor receptor 2 112 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16951187	Inhibitor 8504	3.0 nM [IC50]
Vascular endothelial growth factor receptor 3 41 Target ID: CHEMBL1955 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16951187	Inhibitor 8504	6.0 nM [IC50]
Stem cell growth factor receptor 57 Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16951187	Inhibitor 8504	8.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Non-small cell lung cancer 211 Sources: http://adisinsight.springer.com/drugs/800011016	Primary	Phase III 665	Unknown Approved Use Unknown
Thyroid cancer 17 Sources: http://adisinsight.springer.com/drugs/800011016	Primary	Phase II 1147	Unknown Approved Use Unknown
Ovarian cancer 160 Sources: http://adisinsight.springer.com/drugs/800011016	Primary	Phase II 1147	Unknown Approved Use Unknown
Colorectal cancer 102 Sources: http://adisinsight.springer.com/drugs/800011016	Primary	Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
447 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17557949/	125 mg 1 times / day multiple, oral dose: 125 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MOTESANIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
238 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18574557	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MOTESANIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
2.77 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17557949/	125 mg 1 times / day multiple, oral dose: 125 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MOTESANIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.06 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18574557	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MOTESANIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.24 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17557949/	125 mg 1 times / day multiple, oral dose: 125 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MOTESANIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5.67 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18574557	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MOTESANIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
175 mg 1 times / day multiple, oral Highest studied dose Dose: 175 mg, 1 times / day Route: oral Route: multiple Dose: 175 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17557949	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/17557949	DLT: Fatigue, Hyperbilirubinemia... Dose limiting toxicities: Fatigue (grade 3, 16.7%) Hyperbilirubinemia (grade 3, 16.7%) Encephalopathy (grade 3, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/17557949
125 mg 1 times / day multiple, oral MTD Dose: 125 mg, 1 times / day Route: oral Route: multiple Dose: 125 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23321064	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/23321064	Disc. AE: Posterior reversible encephalopathy syndrome... AEs leading to discontinuation/dose reduction: Posterior reversible encephalopathy syndrome (18.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/23321064
125 mg 1 times / day multiple, oral MTD Dose: 125 mg, 1 times / day Route: oral Route: multiple Dose: 125 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17557949	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/17557949	Sources: https://pubmed.ncbi.nlm.nih.gov/17557949

AEs

AE	Significance	Dose	Population
Encephalopathy	grade 3, 16.7% DLT, Disc. AE	175 mg 1 times / day multiple, oral Highest studied dose Dose: 175 mg, 1 times / day Route: oral Route: multiple Dose: 175 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17557949	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/17557949
Fatigue	grade 3, 16.7% DLT, Disc. AE	175 mg 1 times / day multiple, oral Highest studied dose Dose: 175 mg, 1 times / day Route: oral Route: multiple Dose: 175 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17557949	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/17557949
Hyperbilirubinemia	grade 3, 16.7% DLT, Disc. AE	175 mg 1 times / day multiple, oral Highest studied dose Dose: 175 mg, 1 times / day Route: oral Route: multiple Dose: 175 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17557949	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/17557949
Posterior reversible encephalopathy syndrome	18.2% Disc. AE	125 mg 1 times / day multiple, oral MTD Dose: 125 mg, 1 times / day Route: oral Route: multiple Dose: 125 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23321064	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/23321064

Overview

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

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 910 MRP1 116 CYP1A2 2153 P-gp 1741 MRP7 3	UGT1A1 479 CYP1A1 389 CYP2B6 776 UGT 219 CYP3A5 446 UGT1A4 399 CYP3A7 109

Drug as perpetrator

Target	Modality	Activity
MRP1 232	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/24937702/	no
MRP7 6	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/24937702/	no
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/24462920/	weak [Inhibition 50 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/24462920/	yes [Inhibition 1 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/24462920/	yes [Inhibition 1 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/24462920/	yes [Inhibition 50 uM]
BCRP 985	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/24937702/	yes
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/24937702/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
UGT 219	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/18574557/	major
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19372226/	major
CYP1A1 389	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19372226/	minor
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19372226/	minor
UGT1A1 479	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19372226/	minor
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/18574557/	moderate	yes (co-administration study) Comment: Ketoconazole increased AUC(0-24h) and Cmax by 86% and 35%. Sources: https://pubmed.ncbi.nlm.nih.gov/18574557/
CYP2B6 776	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19372226/	weak
CYP3A5 446	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19372226/	weak
CYP3A7 109	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19372226/	weak

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00D8H0	https://www.1pchem.com/search?query=1P00D8H0
1PlusChem LLC	1P00G31L	https://www.1pchem.com/search?query=1P00G31L
AChemBlock	Q70236	http://www.achemblock.com/catalogsearch/result/?q=Q70236
AK Scientific	SYN1055	https://aksci.com/item_detail.php?cat=SYN1055
AK Scientific	SYN5718	https://aksci.com/item_detail.php?cat=SYN5718
AK Scientific	X4931	https://aksci.com/item_detail.php?cat=X4931
AK Scientific	X7466	https://aksci.com/item_detail.php?cat=X7466
AOBIOUS INC	AOB87176	http://aobious.com/aobious/search?search_query=AOB87176
ApexBio Technology	A3632	https://www.apexbt.com/catalogsearch/result/?q=A3632
ApexBio Technology	A5017	https://www.apexbt.com/catalogsearch/result/?q=A5017
AstaTech	40617	http://astatechinc.com/CPSResult.php?CRNO=40617
AstaTech	61834	http://astatechinc.com/CPSResult.php?CRNO=61834
Axon MedChem	1768	https://www.axonmedchem.com/product/1768
BLD Pharm	BD210719	http://www.bldpharm.com/search/Search.html?keyword=BD210719
BLD Pharm	BD559247	http://www.bldpharm.com/search/Search.html?keyword=BD559247
BOC Sciences	453562-69-1	http://www.bocsci.com/description.asp?cas=453562-69-1
Capot Chemical	22412	https://www.capotchem.com/search.do?q=22412
Cayman Chemical	17671	http://www.caymanchem.com/app/template/Product.vm/catalog/17671
Chem Scene	CS-0028	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0028
Chem Scene	CS-0193	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0193
ChemShuttle	112447	https://www.chemshuttle.com/catalogsearch/result/?q=112447
ChemShuttle	113670	https://www.chemshuttle.com/catalogsearch/result/?q=113670
Combi-Blocks	QJ-0817	http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-0817
eMolecules	31507654	https://orderbb.emolecules.com/search/#?query=31507654
eMolecules	32278026	https://orderbb.emolecules.com/search/#?query=32278026
eMolecules	43639386	https://orderbb.emolecules.com/search/#?query=43639386
eMolecules	48669074	https://orderbb.emolecules.com/search/#?query=48669074
eNovation Chemicals	D388281	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D388281&searchbtn.x=0&searchbtn.y=0
eNovation Chemicals	D518764	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D518764&searchbtn.x=0&searchbtn.y=0
Excenen	EX-A453	http://www.excenen.com/searchresultlist.php?id=EX-A453
Excenen	EX-A487	http://www.excenen.com/searchresultlist.php?id=EX-A487
Exclusive Chemistry	2343	http://www.exchemistry.com/chem-catalog/product-2343.html
Hairui	HR105765	http://www.hairuichem.com/en/product/search.do?q=HR105765
Hairui	HR143778	http://www.hairuichem.com/en/product/search.do?q=HR143778
KeyOrganics	AS-16212	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16212
KeyOrganics	AS-17019	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-17019
Lab Network	LN01299380	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01299380
Lab Seeker	SC-28323	http://www.labseeker.com/search.php?keywords=SC-28323&category=0
LabSeeker	SC-28323	http://www.labseeker.com/search.php?keywords=SC-28323&category=0
Matrix Scientific	132644	http://www.matrixscientific.com/132644.html
Matrix Scientific	147772	http://www.matrixscientific.com/147772.html
mcule	MCULE-3496762093	https://mcule.com/MCULE-3496762093/
mcule	MCULE-4037113225	https://mcule.com/MCULE-4037113225/
mcule	MCULE-9095751100	https://mcule.com/MCULE-9095751100/
MedChem Express	HY-10228	https://www.medchemexpress.com/search.html?q=HY-10228&ft=&fa=&fp=
MedChem Express	HY-10229	https://www.medchemexpress.com/search.html?q=HY-10229&ft=&fa=&fp=
Molnova	M14539	https://www.molnova.com/en/serch-list.html?keywords=M14539
Molnova	M16223	https://www.molnova.com/en/serch-list.html?keywords=M16223
MolPort	MolPort-009-679-440	https://www.molport.com/shop/molecule-link/MolPort-009-679-440
MolPort	MolPort-016-633-170	https://www.molport.com/shop/molecule-link/MolPort-016-633-170
MolPort	MolPort-046-424-798	https://www.molport.com/shop/molecule-link/MolPort-046-424-798
MuseChem	I003594	https://www.musechem.com/product/I003594.html
Ryan Scientific	Motesanib	https://ryansci.com/products?q=Motesanib&list_q=&search_type=exact
Ryan Scientific	TGR5	https://ryansci.com/products?q=TGR5&list_q=&search_type=exact
Selleck Chemicals	S1032	http://www.selleckchem.com/search.html?searchDTO.searchParam=S1032
ShangHai Biochempartner	BCP000220	http://www.biochempartner.com/search_BCP000220
ShangHai Biochempartner	BCP01822	http://www.biochempartner.com/search_BCP01822
ShangHai Biochempartner	BCP01982	http://www.biochempartner.com/search_BCP01982
TargetMol	T2288	https://www.targetmol.com/search?keyword=T2288
TargetMol	T2288L	https://www.targetmol.com/search?keyword=T2288L
Toronto Research Chemicals	A637252	https://www.trc-canada.com/product-detail/?CatNum=A637252
Toronto Research Chemicals	M732500	https://www.trc-canada.com/product-detail/?CatNum=M732500

PubMed

Title	Date	PubMed
Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors.	2012-12-27	23098265
Comprehensive analysis of kinase inhibitor selectivity.	2011-10-30	22037378
Safety and pharmacokinetics of motesanib in combination with panitumumab and gemcitabine-Cisplatin in patients with advanced cancer.	2011	21559248
Targeting RET receptor tyrosine kinase activation in cancer.	2010-12-15	20930041
The lack of target specificity of small molecule anticancer kinase inhibitors is correlated with their ability to damage myocytes in vitro.	2010-12-01	20832415
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.	2010-11-24	21095574
Development of a modeling framework to simulate efficacy endpoints for motesanib in patients with thyroid cancer.	2010-11	20872147
Population pharmacokinetic/pharmacodynamic modeling for the time course of tumor shrinkage by motesanib in thyroid cancer patients.	2010-11	20872145
Biomarkers as predictors of response to treatment with motesanib in patients with progressive advanced thyroid cancer.	2010-11	20739388
Phase 1 study of the investigational, oral angiogenesis inhibitor motesanib in Japanese patients with advanced solid tumors.	2010-10	20107802
Telomerase inhibition targets clonogenic multiple myeloma cells through telomere length-dependent and independent mechanisms.	2010-09-01	20824134
Motesanib inhibits Kit mutations associated with gastrointestinal stromal tumors.	2010-07-15	20633291
Augmentation of radiation response by motesanib, a multikinase inhibitor that targets vascular endothelial growth factor receptors.	2010-07-15	20507929
Axitinib: The evidence of its potential in the treatment of advanced thyroid cancer.	2010-06-15	20694064
Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors.	2010-05-05	20351338
A phase Ib study of AMG 102 in combination with bevacizumab or motesanib in patients with advanced solid tumors.	2010-05-01	20406832
Phase II study of motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate.	2010-04	19690858
Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism of action?	2010-03	20012482
Targeting vascular endothelial growth factor receptor in thyroid cancer: the intracellular and extracellular implications.	2010-02-01	20103668
Phase 1b study of motesanib, an oral angiogenesis inhibitor, in combination with carboplatin/paclitaxel and/or panitumumab for the treatment of advanced non-small cell lung cancer.	2010-01-01	20028752
Present and future evolution of advanced breast cancer therapy.	2010	21050422
Molecular and other novel advances in treatment of metastatic epithelial and medullary thyroid cancers.	2010	20862373
Advances in cellular therapy for the treatment of thyroid cancer.	2010	20671939
Targeting angiogenesis with multitargeted tyrosine kinase inhibitors in the treatment of non-small cell lung cancer.	2010	20427383
Pretargeted radioimmunotherapy in the treatment of metastatic medullary thyroid cancer.	2009-09	19862356
Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer.	2009-08-10	19564535
In vitro metabolism of the novel, highly selective oral angiogenesis inhibitor motesanib diphosphate in preclinical species and in humans.	2009-07	19372226
Targeting RET for thyroid cancer therapy.	2009-02-01	19028457
Broad antitumor activity in breast cancer xenografts by motesanib, a highly selective, oral inhibitor of vascular endothelial growth factor, platelet-derived growth factor, and Kit receptors.	2009-01-01	19118038
[Advances in the treatment of thyroid cancer in the era of molecularly targeted therapies].	2009-01	19211364
Safety and pharmacokinetics of motesanib in combination with gemcitabine for the treatment of patients with solid tumours.	2008-11-04	18971935
Novel therapies in breast cancer: what is new from ASCO 2008.	2008-10-01	18828924
Effect of coadministration of ketoconazole, a strong CYP3A4 inhibitor, on pharmacokinetics and tolerability of motesanib diphosphate (AMG 706) in patients with advanced solid tumors.	2008-10	18574557
New molecular targeted therapies in thyroid cancer.	2006-09	16940797

Patents

Sample Use Guides

In Vivo Use Guide

50-125 mg per day. Motesanib appeared to induce a dose-dependent biological response in an ongoing phase I trial in patients with advanced solid tumours. A reduction in soluble VEGF-receptor 2 (KDR) correlated with the change in tumour size at day 50. In a phase II trial, motesanib at doses up to 125 mg/day showed anti-tumour activity among patients with advanced malignancy.

Route of Administration: Oral

In Vitro Use Guide

Motesanib (AMG-706) potently inhibited VEGF-induced proliferation of HUVECs with IC50 values of 10 nM

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:45:29 GMT 2025` Edited by `admin` on `Mon Mar 31 18:45:29 GMT 2025`
Record UNII	U1JK633AYI
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AMG 706

Preferred Name

English

MOTESANIB

Official Name

English

AMG-706

Code

English

N-(3,3-Dimethyl-2,3-dihydro-1H-indol-6-yl)-2-[(pyridin-4-ylmethyl)amino]pyridine-3-carboxamide

Systematic Name

English

N-(3,3-DIMETHYL-2,3-DIHYDRO-1H-INDOL-6-YL)-2-((PYRIDIN-4-YLMETHYL)AMINO)NICOTINAMIDE

Systematic Name

English

MOTESANIB [USAN]

Common Name

English

3-PYRIDINECARBOXAMIDE, N-(2,3-DIHYDRO-3,3-DIMETHYL-1H-INDOL-6-YL)-2-((4-PYRIDINYLMETHYL)AMINO)-

Systematic Name

English

MOTESANIB [MART.]

Common Name

English

motesanib [INN]

Common Name

English

Motesanib [WHO-DD]

Common Name

English

MOTESANIB [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1967