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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 of MOTESANIB

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
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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
447 ng/mL
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
2.77 μg × h/mL
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
6.24 h
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
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

Doses

DosePopulationAdverse 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:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
DLT: Fatigue, Hyperbilirubinemia...
Dose limiting toxicities:
Fatigue (grade 3, 16.7%)
Hyperbilirubinemia (grade 3, 16.7%)
Encephalopathy (grade 3, 16.7%)
Sources:
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:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
Disc. AE: Posterior reversible encephalopathy syndrome...
AEs leading to
discontinuation/dose reduction:
Posterior reversible encephalopathy syndrome (18.2%)
Sources:
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:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
AEs

AEs

AESignificanceDosePopulation
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:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
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:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
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:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
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:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
OverviewDrug as perpetrator​Drug as victim
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
New molecular targeted therapies in thyroid cancer.
2006 Sep
Safety and pharmacokinetics of motesanib in combination with gemcitabine for the treatment of patients with solid tumours.
2008 Nov 4
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 Oct
Novel therapies in breast cancer: what is new from ASCO 2008.
2008 Oct 1
Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer.
2009 Aug 10
Targeting RET for thyroid cancer therapy.
2009 Feb 1
[Advances in the treatment of thyroid cancer in the era of molecularly targeted therapies].
2009 Jan
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 Jan 1
Present and future evolution of advanced breast cancer therapy.
2010
Targeting RET receptor tyrosine kinase activation in cancer.
2010 Dec 15
Targeting vascular endothelial growth factor receptor in thyroid cancer: the intracellular and extracellular implications.
2010 Feb 1
Development of a modeling framework to simulate efficacy endpoints for motesanib in patients with thyroid cancer.
2010 Nov
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
2010 Nov 24
Safety and pharmacokinetics of motesanib in combination with panitumumab and gemcitabine-Cisplatin in patients with advanced cancer.
2011
Comprehensive analysis of kinase inhibitor selectivity.
2011 Oct 30
Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors.
2012 Dec 27
Patents

Sample Use Guides

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
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
  • Download
Name Type Language
AMG 706
Preferred Name English
MOTESANIB
INN   MART.   MI   USAN   WHO-DD  
USAN   INN  
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
Created by admin on Mon Mar 31 18:45:29 GMT 2025 , Edited by admin on Mon Mar 31 18:45:29 GMT 2025
Code System Code Type Description
CAS
453562-69-1
Created by admin on Mon Mar 31 18:45:29 GMT 2025 , Edited by admin on Mon Mar 31 18:45:29 GMT 2025
PRIMARY
EPA CompTox
DTXSID10196488
Created by admin on Mon Mar 31 18:45:29 GMT 2025 , Edited by admin on Mon Mar 31 18:45:29 GMT 2025
PRIMARY
MERCK INDEX
m7636
Created by admin on Mon Mar 31 18:45:29 GMT 2025 , Edited by admin on Mon Mar 31 18:45:29 GMT 2025
PRIMARY Merck Index
ChEMBL
CHEMBL572881
Created by admin on Mon Mar 31 18:45:29 GMT 2025 , Edited by admin on Mon Mar 31 18:45:29 GMT 2025
PRIMARY
NCI_THESAURUS
C71896
Created by admin on Mon Mar 31 18:45:29 GMT 2025 , Edited by admin on Mon Mar 31 18:45:29 GMT 2025
PRIMARY
SMS_ID
100000141571
Created by admin on Mon Mar 31 18:45:29 GMT 2025 , Edited by admin on Mon Mar 31 18:45:29 GMT 2025
PRIMARY
INN
8828
Created by admin on Mon Mar 31 18:45:29 GMT 2025 , Edited by admin on Mon Mar 31 18:45:29 GMT 2025
PRIMARY
WIKIPEDIA
MOTESANIB
Created by admin on Mon Mar 31 18:45:29 GMT 2025 , Edited by admin on Mon Mar 31 18:45:29 GMT 2025
PRIMARY
USAN
SS-13
Created by admin on Mon Mar 31 18:45:29 GMT 2025 , Edited by admin on Mon Mar 31 18:45:29 GMT 2025
PRIMARY
DRUG BANK
DB05575
Created by admin on Mon Mar 31 18:45:29 GMT 2025 , Edited by admin on Mon Mar 31 18:45:29 GMT 2025
PRIMARY
EVMPD
SUB93453
Created by admin on Mon Mar 31 18:45:29 GMT 2025 , Edited by admin on Mon Mar 31 18:45:29 GMT 2025
PRIMARY
FDA UNII
U1JK633AYI
Created by admin on Mon Mar 31 18:45:29 GMT 2025 , Edited by admin on Mon Mar 31 18:45:29 GMT 2025
PRIMARY
PUBCHEM
11667893
Created by admin on Mon Mar 31 18:45:29 GMT 2025 , Edited by admin on Mon Mar 31 18:45:29 GMT 2025
PRIMARY
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