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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
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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
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Hazard and Precautionary Statements (GHS)

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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
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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

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Sitravatinib Suppliers

China 76 India 2 United States 13 Global 91
Suzhou Meidi Senuo Pharmaceutical Technology Co., Ltd.
Tel
13771642864
Fax
1078336263
Email
snhuyu_2008@126.com
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China
ProdList
1165
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58
Dalian Meilun Biotech Co., Ltd.
Tel
0411-62910999 13889544652
Email
sales@meilune.com
Country
China
ProdList
4747
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58
MedChemexpress LLC
Tel
021-58955995
Fax
609-228-5909
Email
sales@medchemexpress.cn
Country
United States
ProdList
4861
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58
Shanghai Lollane Biological Technology Co.,Ltd.
Tel
021-52996696，15000506266 15000506266
Fax
+86-21-52996696
Country
China
ProdList
4757
Advantage
55
Shanghai YuanYe Biotechnology Co., Ltd.
Tel
021-61312847; 18021002903
Fax
QQ:3008007432
Email
3008007409@qq.com
Country
China
ProdList
71826
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60
Qingdao IniKem BioPharmaTech Co.,Ltd
Tel
0532-58268780 18561687109;
Fax
-
Email
sales@inikem.com
Country
China
ProdList
298
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55
ShangHai Biochempartner Co.,Ltd
Tel
177-54423994 17754423994
Fax
QQ:2853530913
Email
2853530910@QQ.com
Country
China
ProdList
8000
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Shanghai Rechem science Co., Ltd.
Tel
021-31433387 15618786686
Fax
QQ:1369748377
Email
sales@rechemscience.com
Country
China
ProdList
2987
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58
Shanghai Zhixin Chemical Technology Co., Ltd.
Tel
18701958033
Fax
021-60441077
Email
shzxchem@163.com
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China
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649
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58
Amadis Chemical Company Limited
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571-89925085
Fax
0086-571-89925065
Email
sales@amadischem.com
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China
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131957
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58

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