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Details

Stereochemistry ACHIRAL
Molecular Formula C22H23N5O
Molecular Weight 373.4517
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MOTESANIB

SMILES

CC1(C)CNc2cc(ccc21)N=C(c3cccnc3NCc4ccncc4)O

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 373.4517
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: 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
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
In vitro metabolism of the novel, highly selective oral angiogenesis inhibitor motesanib diphosphate in preclinical species and in humans.
2009 Jul
Pretargeted radioimmunotherapy in the treatment of metastatic medullary thyroid cancer.
2009 Sep
Present and future evolution of advanced breast cancer therapy.
2010
Molecular and other novel advances in treatment of metastatic epithelial and medullary thyroid cancers.
2010
Advances in cellular therapy for the treatment of thyroid cancer.
2010
Targeting angiogenesis with multitargeted tyrosine kinase inhibitors in the treatment of non-small cell lung cancer.
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
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
Motesanib inhibits Kit mutations associated with gastrointestinal stromal tumors.
2010 Jul 15
Augmentation of radiation response by motesanib, a multikinase inhibitor that targets vascular endothelial growth factor receptors.
2010 Jul 15
Axitinib: The evidence of its potential in the treatment of advanced thyroid cancer.
2010 Jun 15
Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism of action?
2010 Mar
Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors.
2010 May 5
Development of a modeling framework to simulate efficacy endpoints for motesanib in patients with thyroid cancer.
2010 Nov
Population pharmacokinetic/pharmacodynamic modeling for the time course of tumor shrinkage by motesanib in thyroid cancer patients.
2010 Nov
Biomarkers as predictors of response to treatment with motesanib in patients with progressive advanced thyroid cancer.
2010 Nov
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
Telomerase inhibition targets clonogenic multiple myeloma cells through telomere length-dependent and independent mechanisms.
2010 Sep 1
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 Sat Jun 26 04:26:29 UTC 2021
Edited
by admin
on Sat Jun 26 04:26:29 UTC 2021
Record UNII
U1JK633AYI
Record Status Validated (UNII)
Record Version
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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)NICOTINAMIDE
Systematic Name English
MOTESANIB [WHO-DD]
Common 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 [MI]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1967
Created by admin on Sat Jun 26 04:26:30 UTC 2021 , Edited by admin on Sat Jun 26 04:26:30 UTC 2021
Code System Code Type Description
CAS
453562-69-1
Created by admin on Sat Jun 26 04:26:30 UTC 2021 , Edited by admin on Sat Jun 26 04:26:30 UTC 2021
PRIMARY
EPA CompTox
453562-69-1
Created by admin on Sat Jun 26 04:26:30 UTC 2021 , Edited by admin on Sat Jun 26 04:26:30 UTC 2021
PRIMARY
MERCK INDEX
M7636
Created by admin on Sat Jun 26 04:26:30 UTC 2021 , Edited by admin on Sat Jun 26 04:26:30 UTC 2021
PRIMARY Merck Index
ChEMBL
CHEMBL572881
Created by admin on Sat Jun 26 04:26:30 UTC 2021 , Edited by admin on Sat Jun 26 04:26:30 UTC 2021
PRIMARY
NCI_THESAURUS
C71896
Created by admin on Sat Jun 26 04:26:30 UTC 2021 , Edited by admin on Sat Jun 26 04:26:30 UTC 2021
PRIMARY
INN
8828
Created by admin on Sat Jun 26 04:26:30 UTC 2021 , Edited by admin on Sat Jun 26 04:26:30 UTC 2021
PRIMARY
WIKIPEDIA
MOTESANIB
Created by admin on Sat Jun 26 04:26:30 UTC 2021 , Edited by admin on Sat Jun 26 04:26:30 UTC 2021
PRIMARY
DRUG BANK
DB05575
Created by admin on Sat Jun 26 04:26:30 UTC 2021 , Edited by admin on Sat Jun 26 04:26:30 UTC 2021
PRIMARY
EVMPD
SUB93453
Created by admin on Sat Jun 26 04:26:30 UTC 2021 , Edited by admin on Sat Jun 26 04:26:30 UTC 2021
PRIMARY
FDA UNII
U1JK633AYI
Created by admin on Sat Jun 26 04:26:30 UTC 2021 , Edited by admin on Sat Jun 26 04:26:30 UTC 2021
PRIMARY
PUBCHEM
11667893
Created by admin on Sat Jun 26 04:26:30 UTC 2021 , Edited by admin on Sat Jun 26 04:26:30 UTC 2021
PRIMARY
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