ChemicalBook > CAS DataBase List > Sitravatinib

Sitravatinib

Product Name
Sitravatinib
CAS No.
1123837-84-2
Chemical Name
Sitravatinib
Synonyms
MG516;CS-2638;MGCD-516;Sitravatinib;MGCD516 (SITRAVATINIB);Sitravatinib (MGCD516);Sitravatinib, 10 mM in DMSO;N-(3-fluoro-4-((2-(5-(((2-methoxyethyl)amino)methyl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yl)oxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide;1,1-Cyclopropanedicarboxamide, N-[3-fluoro-4-[[2-[5-[[(2-methoxyethyl)amino]methyl]-2-pyridinyl]thieno[3,2-b]pyridin-7-yl]oxy]phenyl]-N'-(4-fluorophenyl)-;RTK,MG-516,PD-1,SCFR,DDR1,inhibit,VEGFR2,MG 516,MGCD 516,MER,immune,TRKA,Cluster of differentiation antigen 135,Cancer,Discoidin Domain Receptor,VEGFR3,Inhibitor,Vascular endothelial growth factor receptor,Trk Receptor,Tropomyosin related kinase receptor,CD135,VEGFR,immunotherapy,Macrophages,c-Kit,DDR2,VEGFR1,Tyrosine,Fms like tyrosine kinase 3,FLT3,Axl,TRKB,Sitravatinib,MGCD-516,KIT,kinase,CD117
CBNumber
CB03128970
Molecular Formula
C33H29F2N5O4S
Formula Weight
629.68
MOL File
1123837-84-2.mol
More
Less

Sitravatinib Property

Boiling point:
833.5±65.0 °C(Predicted)
Density 
1.417±0.06 g/cm3(Predicted)
storage temp. 
-20°C
solubility 
Soluble in DMSO (up to at least 25 mg/ml), or in Ethanol (up to at least 25 mg/ml)
form 
solid
pka
13.17±0.70(Predicted)
color 
Off-white
Stability:
Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 1 month.
InChIKey
WLAVZAAODLTUSW-UHFFFAOYSA-N
SMILES
C1(C(NC2=CC=C(F)C=C2)=O)(C(NC2=CC=C(OC3C=CN=C4C=C(C5=NC=C(CNCCOC)C=C5)SC4=3)C(F)=C2)=O)CC1
More
Less

Hazard and Precautionary Statements (GHS)

More
Less

N-Bromosuccinimide Price

Cayman Chemical
Product number
27338
Product name
Sitravatinib
Packaging
5mg
Price
$57
Updated
2024/03/01
Cayman Chemical
Product number
27338
Product name
Sitravatinib
Packaging
10mg
Price
$107
Updated
2024/03/01
Cayman Chemical
Product number
27338
Product name
Sitravatinib
Packaging
25mg
Price
$233
Updated
2024/03/01
Cayman Chemical
Product number
27338
Product name
Sitravatinib
Packaging
50mg
Price
$437
Updated
2024/03/01
Usbiological
Product number
456189
Product name
MGCD 516
Packaging
10mg
Price
$425
Updated
2021/12/16
More
Less

Sitravatinib Chemical Properties,Usage,Production

Description

Sitravatinib is a multi-kinase inhibitor. It inhibits 35 kinases (IC50s = 0.5-5,550 nM) in a panel of 55 receptor tyrosine kinases (RTKs). Sitravatinib reduces proliferation of A-673, LPS141, MPNST, DDLS, and Saos-2 cancer cells (IC50s = 1,750, 340.1, 705.7, 266, and 1,830 nM, respectively) and decreases phosphorylation of insulin-like growth factor 1 receptor (IGF1-R), PDGFRβ, and Akt in these same cells when used at concentrations ranging from 62.5 to 4,000 nM. It decreases tumor growth in LPS141 and MPNST mouse xenograft models when administered at a dose of 15 mg/kg per day.

Description

Sitravatinib, known as MGCD516, is a multikinase (MET, RET, AXL, NTRK1, or NTRK3 genes) inhibitor used in a phase 1/1b clinical trial (NCT02219711) for patients with advanced cancers (NCT02219711).

Uses

MGCD 516 is an intermediate used to prepare substituted thienopyridines as inhibitors of protein tyrosine kinase activity.

Synthesis

1123837-39-7

1123837-84-2

Step 2. Synthesis of N-(3-fluoro-4-((2-(5-(((2-methoxyethyl)amino)methyl)pyridin-2-yl)thieno[3,2-b]pyridin-7- yl)oxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1 -dicarboxamide (147): Compound 146 (0.59 g, 0.81 mmol) was dissolved in dichloromethane (50 mL) in dichloromethane (50 mL) and trifluoroacetic acid (TFA, 3 mL) was added. The reaction mixture was stirred at room temperature for 18 hours. Upon completion of the reaction, the solution was concentrated to remove the solvent. The residue was partitioned between dichloromethane and 1 M sodium hydroxide solution and filtered to remove insoluble impurities. The organic phase was separated, washed sequentially with 1 M sodium hydroxide solution and saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated to afford the target compound 147 (0.35 g, 69% yield).1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.40 (s, 1H), 10.01 (s, 1H), 8.55 (d, J = 1.6 Hz 1H), 8.51 (d, J = 5.3 Hz, 1H), 8.31 (s, 1H), 8.22 (d, J = 8.0 Hz, 1H), 7.92-7.87 (m, 2H), 7.65-7.61 (m, 2H), 7.52-7.43 (m, 2H), 7.17-7.12 (m, 2H), 6.64 (d, J = 5.5 Hz, 1H), 3.77 (s, 2H), 3.40 (t, J = 5.7 Hz, 2H), 3.23 (s, 3H), 2.64 (t, J = 5.7 Hz, 2H), 1.46 (br s, 4H). Mass spectrum (m/z): 630.1 (M + H).

in vivo

Sitravatinib (20 mg/kg; p.o.; once per day for 6 days) significantly inhibits tumor progression and induces tumor regression in C57BL/6 mice bearing CT1B-A5 cells model[2].

Animal Model:6-week-old C57BL/6 mice (bearing CT1B-A5 cells) [2]
Dosage:20 mg/kg
Administration:Oral administration; once per day for 6 days
Result:Significantly inhibited tumor progression and induced tumor regression.

IC 50

Axl: 1.5 nM (IC50); MER: 2 nM (IC50); VEGFR3: 2 nM (IC50); VEGFR2: 5 nM (IC50); VEGFR1: 6 nM (IC50); TrkA: 5 nM (IC50); TrkB: 9 nM (IC50); KIT: 6 nM (IC50); FLT3: 8 nM (IC50); DDR2: 0.5 nM (IC50); DDR1: 29 nM (IC50)

References

[1] PARAG P. PATWARDHAN. Significant blockade of multiple receptor tyrosine kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma[J]. Oncotarget, 2015, 7 1: 4093-4109. DOI:10.18632/oncotarget.6547
[2] T. LEAL. MA 02.01 Evidence of Clinical Activity of Sitravatinib in Combination with Nivolumab in NSCLC Patients Progressing on Prior Checkpoint Inhibitors[J]. Journal of Thoracic Oncology, 2017. DOI:10.1016/j.jtho.2017.09.451
[3] WENTING DU. Sitravatinib potentiates immune checkpoint blockade in refractory cancer models.[J]. JCI insight, 2018. DOI:10.1172/jci.insight.124184

Sitravatinib Preparation Products And Raw materials

Raw materials

Preparation Products

More
Less

Sitravatinib Suppliers

China 76 India 2 United States 13 Global 91
MedChemexpress LLC
Tel
021-58955995
Fax
609-228-5909
Email
sales@medchemexpress.cn
Country
United States
ProdList
4861
Advantage
58
Musechem
Tel
+1-800-259-7612
Fax
+1-800-259-7612
Email
info@musechem.com
Country
United States
ProdList
4660
Advantage
60
TargetMol Chemicals Inc.
Tel
+1-781-999-5354; +17819995354
Email
marketing@targetmol.com
Country
United States
ProdList
32435
Advantage
58
InvivoChem
Tel
+1-708-310-1919 +1-13798911105
Fax
708-557-7486
Email
sales@invivochem.cn
Country
United States
ProdList
6391
Advantage
58
Cckinase, Inc.
Tel
+1 (732)236-3202
Email
sales@cckinase.com
Country
United States
ProdList
2738
Advantage
58
Aladdin Scientific
Tel
Email
tp@aladdinsci.com
Country
United States
ProdList
57505
Advantage
58
TargetMol Chemicals Inc.
Tel
+1-781-999-5354;
Email
support@targetmol.com
Country
United States
ProdList
39035
Advantage
58
United States Biological
Tel
--
Fax
--
Email
sales@advtechind.com
Country
United States
ProdList
6075
Advantage
58
BOC Sciences
Tel
16314854226
Email
info@bocsci.com
Country
United States
ProdList
9923
Advantage
65
Focus Biomolecules
Tel
--
Fax
--
Email
sales@focusbiomolecules.com
Country
United States
ProdList
1284
Advantage
58
Abcam Limited
Tel
--
Fax
--
Email
us.orders@abcam.com
Country
United States
ProdList
6001
Advantage
50
Cayman Chemical Company
Tel
--
Fax
--
Email
cayman@caymanchem.com
Country
United States
ProdList
6213
Advantage
81
United States Biological
Tel
--
Fax
--
Email
chemicals@usbio.net
Country
United States
ProdList
6214
Advantage
80

1123837-84-2, SitravatinibRelated Search:

Sivelestat sodium Adapalene SU 4312 Geldanamycin Troglitazone Skepinone-L Sitaxentan sodium

  • CS-2638
  • Sitravatinib
  • N-(3-fluoro-4-((2-(5-(((2-methoxyethyl)amino)methyl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yl)oxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
  • MGCD-516
  • MG516
  • Sitravatinib (MGCD516)
  • 1,1-Cyclopropanedicarboxamide, N-[3-fluoro-4-[[2-[5-[[(2-methoxyethyl)amino]methyl]-2-pyridinyl]thieno[3,2-b]pyridin-7-yl]oxy]phenyl]-N'-(4-fluorophenyl)-
  • RTK,MG-516,PD-1,SCFR,DDR1,inhibit,VEGFR2,MG 516,MGCD 516,MER,immune,TRKA,Cluster of differentiation antigen 135,Cancer,Discoidin Domain Receptor,VEGFR3,Inhibitor,Vascular endothelial growth factor receptor,Trk Receptor,Tropomyosin related kinase receptor,CD135,VEGFR,immunotherapy,Macrophages,c-Kit,DDR2,VEGFR1,Tyrosine,Fms like tyrosine kinase 3,FLT3,Axl,TRKB,Sitravatinib,MGCD-516,KIT,kinase,CD117
  • MGCD516 (SITRAVATINIB)
  • Sitravatinib, 10 mM in DMSO
  • 1123837-84-2
  • C33H29F2N5O4S