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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=C1C=CC(NC(=O)C3=CC=CN=C3NCC4=CC=NC=C4)=C2

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
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: Page: p.2371
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.2371
DLT: Encephalopathy, Fatigue...
Dose limiting toxicities:
Encephalopathy (grade 3, 16.7%)
Fatigue (grade 3, 16.7%)
Hyperbilirubinemia (grade 3, 16.7%)
Sources: Page: p.2371
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: Page: p.5
unhealthy, ADULT
n = 22
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Population Size: 22
Sources: Page: p.5
Disc. AE: Posterior reversible encephalopathy syndrome...
AEs leading to
discontinuation/dose reduction:
Posterior reversible encephalopathy syndrome (18.2%)
Sources: Page: p.5
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: Page: p.2371
unhealthy, ADULT
n = 28
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 28
Sources: Page: p.2371
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: Page: p.2371
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.2371
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: Page: p.2371
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.2371
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: Page: p.2371
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.2371
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: Page: p.5
unhealthy, ADULT
n = 22
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Population Size: 22
Sources: Page: p.5
OverviewDrug as perpetrator​Drug as victim
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer.
2009 Aug 10
[Advances in the treatment of thyroid cancer in the era of molecularly targeted therapies].
2009 Jan
In vitro metabolism of the novel, highly selective oral angiogenesis inhibitor motesanib diphosphate in preclinical species and in humans.
2009 Jul
Present and future evolution of advanced breast cancer therapy.
2010
Phase II study of motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate.
2010 Apr
The lack of target specificity of small molecule anticancer kinase inhibitors is correlated with their ability to damage myocytes in vitro.
2010 Dec 1
Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors.
2010 May 5
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
2010 Nov 24
Phase 1 study of the investigational, oral angiogenesis inhibitor motesanib in Japanese patients with advanced solid tumors.
2010 Oct
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 Fri Dec 15 17:23:00 GMT 2023
Edited
by admin
on Fri Dec 15 17:23:00 GMT 2023
Record UNII
U1JK633AYI
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
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
AMG 706
Code 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 Fri Dec 15 17:23:00 GMT 2023 , Edited by admin on Fri Dec 15 17:23:00 GMT 2023
Code System Code Type Description
CAS
453562-69-1
Created by admin on Fri Dec 15 17:23:00 GMT 2023 , Edited by admin on Fri Dec 15 17:23:00 GMT 2023
PRIMARY
EPA CompTox
DTXSID10196488
Created by admin on Fri Dec 15 17:23:00 GMT 2023 , Edited by admin on Fri Dec 15 17:23:00 GMT 2023
PRIMARY
MERCK INDEX
m7636
Created by admin on Fri Dec 15 17:23:00 GMT 2023 , Edited by admin on Fri Dec 15 17:23:00 GMT 2023
PRIMARY Merck Index
ChEMBL
CHEMBL572881
Created by admin on Fri Dec 15 17:23:00 GMT 2023 , Edited by admin on Fri Dec 15 17:23:00 GMT 2023
PRIMARY
NCI_THESAURUS
C71896
Created by admin on Fri Dec 15 17:23:00 GMT 2023 , Edited by admin on Fri Dec 15 17:23:00 GMT 2023
PRIMARY
SMS_ID
100000141571
Created by admin on Fri Dec 15 17:23:00 GMT 2023 , Edited by admin on Fri Dec 15 17:23:00 GMT 2023
PRIMARY
INN
8828
Created by admin on Fri Dec 15 17:23:00 GMT 2023 , Edited by admin on Fri Dec 15 17:23:00 GMT 2023
PRIMARY
WIKIPEDIA
MOTESANIB
Created by admin on Fri Dec 15 17:23:00 GMT 2023 , Edited by admin on Fri Dec 15 17:23:00 GMT 2023
PRIMARY
USAN
SS-13
Created by admin on Fri Dec 15 17:23:00 GMT 2023 , Edited by admin on Fri Dec 15 17:23:00 GMT 2023
PRIMARY
DRUG BANK
DB05575
Created by admin on Fri Dec 15 17:23:00 GMT 2023 , Edited by admin on Fri Dec 15 17:23:00 GMT 2023
PRIMARY
EVMPD
SUB93453
Created by admin on Fri Dec 15 17:23:00 GMT 2023 , Edited by admin on Fri Dec 15 17:23:00 GMT 2023
PRIMARY
FDA UNII
U1JK633AYI
Created by admin on Fri Dec 15 17:23:00 GMT 2023 , Edited by admin on Fri Dec 15 17:23:00 GMT 2023
PRIMARY
PUBCHEM
11667893
Created by admin on Fri Dec 15 17:23:00 GMT 2023 , Edited by admin on Fri Dec 15 17:23:00 GMT 2023
PRIMARY
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