Home > Compound List > Compound details
319460-85-0 molecular structure
click picture or here to close

N-methyl-2-({3-[(E)-2-(pyridin-2-yl)ethenyl]-1H-indazol-6-yl}sulfanyl)benzamide

ChemBase ID: 72454
Molecular Formular: C22H18N4OS
Molecular Mass: 386.46952
Monoisotopic Mass: 386.12013222
SMILES and InChIs

SMILES:
c1(ccccc1C(=O)NC)Sc1cc2c(cc1)c(n[nH]2)/C=C/c1ccccn1
Canonical SMILES:
CNC(=O)c1ccccc1Sc1ccc2c(c1)[nH]nc2/C=C/c1ccccn1
InChI:
InChI=1S/C22H18N4OS/c1-23-22(27)18-7-2-3-8-21(18)28-16-10-11-17-19(25-26-20(17)14-16)12-9-15-6-4-5-13-24-15/h2-14H,1H3,(H,23,27)(H,25,26)/b12-9+
InChIKey:
RITAVMQDGBJQJZ-FMIVXFBMSA-N

Cite this record

CBID:72454 http://www.chembase.cn/molecule-72454.html

Collapse All Expand All

NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
N-methyl-2-({3-[(E)-2-(pyridin-2-yl)ethenyl]-1H-indazol-6-yl}sulfanyl)benzamide
N-methyl-2-({3-[2-(pyridin-2-yl)ethenyl]-1H-indazol-6-yl}sulfanyl)benzamide
IUPAC Traditional name
axitinib
N-methyl-2-({3-[2-(pyridin-2-yl)ethenyl]-1H-indazol-6-yl}sulfanyl)benzamide
Synonyms
N-Methyl-2-[[3-[(1E)-2-(2-pyridinyl)ethenyl]-1H-indazol-6-yl]thio]benzamide
AG 013736
AG-013736
Axitinib
N-Methyl-2-((3-((1E)-2-(pyridin-2-yl)ethenyl)-1H-indazol-6-yl)sulfanyl)benzamide
Axitinib
(E)-N-Methyl-2-((3-(2-(pyridin-2-yl)vinyl)-1H-indazol-6-yl)thio)benzamide
CAS Number
319460-85-0
MDL Number
MFCD09837898
PubChem SID
162037379
PubChem CID
6450551

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem
Acid pKa 13.477197  H Acceptors
H Donor LogD (pH = 5.5) 4.1001434 
LogD (pH = 7.4) 4.1482124  Log P 4.1488643 
Molar Refractivity 115.136 cm3 Polarizability 44.266933 Å3
Polar Surface Area 70.67 Å2 Rotatable Bonds
Lipinski's Rule of Five true 

PROPERTIES

PROPERTIES

Physical Property Safety Information Pharmacology Properties Product Information Bioassay(PubChem)
Solubility
DMSO expand Show data source
DMSO: ≥8 mg/mL expand Show data source
Methanol expand Show data source
Apperance
Off-White Solid expand Show data source
white to tan powder expand Show data source
Melting Point
226-228°C expand Show data source
Storage Condition
-20°C expand Show data source
-20°C Freezer expand Show data source
MSDS Link
Download expand Show data source
Download expand Show data source
Storage Temperature
room temp expand Show data source
Target
c-Kit expand Show data source
PDGFR expand Show data source
VEGFR expand Show data source
Purity
≥98% (HPLC) expand Show data source
95+% expand Show data source
Salt Data
Free Base expand Show data source
Certificate of Analysis
Download expand Show data source
Empirical Formula (Hill Notation)
C22H18N4OS expand Show data source

DETAILS

DETAILS

Selleck Chemicals Selleck Chemicals Sigma Aldrich Sigma Aldrich TRC TRC
Selleck Chemicals - S1005 external link
Research Area
Description Cancer
Biological Activity
Description Axitinib (AG-013736) is a multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ and c-Kit with IC50 of 0.1 nM, 0.2 nM, 0.1-0.3 nM, 1.6 nM and 1.7 nM, respectively.
Targets VEGFR1 VEGFR2 VEGFR3 PDGFRβ c-Kit
IC50 0.1 nM 0.2 nM 0.1-0.3 nM 1.6 nM 1.7 nM [1]
In Vitro Axitinib could block the cellular autophosphorylation of VEGFR and VEGF-mediated endothelial cell viability, tube formation, and downstream signaling. Axitinib inhibits the proliferation of variable cell lines with IC50 of >10,000 nM (IGR-N91), 849 nM (IGR-NB8), 274 nM (SH-SY5Y) and 573 nM (non-VEGF stimulated HUVEC). [2]
In Vivo Axitinib exhibits primary inhibition to orthotopically transplanted models such as M24met (melanoma), HCT-116 (colorectal cancer), and SN12C (renal cell carcinoma). [1] Axitinib delays the tumor growth with 11.4 days compared to the controls (p.o. 30 mg/kg) and decreases the Mean Vessels Density (MVD) to 21, compared to 49 in controls, in IGR-N91 ?ank xenografts. [2] Axitinib significantly inhibits growth and disrupts tumor microvasculature in BT474 breast cancer model at 10-100 mg/kg. [3] Axitinib has shown single-agent activity in variable tumors, including renal cell carcinoma, thyroid cancer, non-small cell lung cancer, and melanoma.
Clinical Trials Axitinib is currently in Phase III clinical trial in advanced hepatocellular carcinoma.
Features Axitinib is superior as second-line therapy compared with sorafenib, the current standard of care.
Combination Therapy
Description Axitinib orally administrated twice daily at dose of 10 or 30 mg/kg in combination with a maximally tolerated dose of Docetaxel (40 mg/kg once a week) enhance tumor growth delay in the LLC model. Axitinib orally administrated twice daily at dose of 30 mg/kg in combination with Docetaxel at dose of 5 mg/kg produce a robust tumor growth delay in the MDA-MB-435/HAL-luc model. Axitinib orally administrated twice daily at dose of 30 mg/kg in combination with Gemcitabine at dose of 140 mg/kg (i.p., days 1, 4, 7, and 10) significantly enhance the effect of tumor growth delay in the Gemcitabine-resistant BxPC-3 human pancreatic cancer model. [1]
Protocol
Kinase Assay [1]
Cellular receptor kinase phosphorylation assay Porcine aorta endothelial (PAE) cells, which overexpress full-length VEGFR2, PDGFRβ, Kit, and NIH-3T3, which overexpress murine VEGFR2 (Flk-1) or PDGFRα, are generated. The 96-well plates are coated with 100 μL/well of 2.5 μg/mL anti-VEGFR2 antibody, 0.75 μg/mL anti-PDGFRβ antibody, 0.25 μg/mL anti-PDGFRα antibody, 0.5 μg/mL anti-KIT antibody, or 1.20 μg/mL anti-Flk-1 antibody to prepare ELISA capture plates. Then phosphorylation of RTK is measured by ELISA.
Cell Assay [2]
Cell Lines HUVEC, SH-SY5Y, IGR-N91 and IGR-NB8 cells
Concentrations 1 nM - 10 μM
Incubation Time 72 hours
Methods Cells are seeded in a 96-well plate at a density of 5 × 104 and cultured for 24 hours. Axitinib is added to the cells at concentrations ranging from 1 nM to 10 μM. Cell viability is measured after 72 hours by MTS tetrazolium substrate and IC50 values are calculated.
Animal Study [3]
Animal Models BT474 breast cancer cells are implanted subcutaneously into Immune-deficient female mice (Nu/nu; age 8–12 weeks).
Formulation 0.5% carboxymethylcellulose (CMC)
Doses 10, 30 or 100 mg/kg
Administration Oral daily
References
[1] Hu-Lowe DD, et al. Clin Cancer Res, 2008, 14(22), 7272-7283.
[2] Rossler, J. et al., Int J Cancer, 2011, 128(11), 2748-2758.
[3] Wilmes LJ, et al. Magn Reson Imaging, 2007, 25 (3), 319-327.
Sigma Aldrich - PZ0193 external link
Legal Information
Sold for research purposes under agreement from Pfizer Inc.
Biochem/physiol Actions
Axitinib (AG-013736) is an orally available, potent (picomolar) and selective tyrosine kinase inhibitor that blocks VEGF receptors 1, 2 and 3. The drug blocks VEGF-mediated endothelial cell survival, tube formation, and downstream signaling through endothelial nitric oxide synthase, Akt and extracellular signal-regulated kinase.
Toronto Research Chemicals - A794650 external link
Axitinib is a tyrosine kinase inhibitor. Axitinib is used in cancer therapy.

REFERENCES

REFERENCES

From Suppliers Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
  • Searching...Please wait...

PATENTS

PATENTS

PubChem iconPubChem Patent Google Patent Search IconGoogle Patent

INTERNET

INTERNET

Baidu iconBaidu google iconGoogle