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Details

Stereochemistry ACHIRAL
Molecular Formula C33H29F2N5O4S
Molecular Weight 629.676
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SITRAVATINIB

SMILES

COCCNCC1=CN=C(C=C1)C2=CC3=NC=CC(OC4=CC=C(NC(=O)C5(CC5)C(=O)NC6=CC=C(F)C=C6)C=C4F)=C3S2

InChI

InChIKey=WLAVZAAODLTUSW-UHFFFAOYSA-N
InChI=1S/C33H29F2N5O4S/c1-43-15-14-36-18-20-2-8-25(38-19-20)29-17-26-30(45-29)28(10-13-37-26)44-27-9-7-23(16-24(27)35)40-32(42)33(11-12-33)31(41)39-22-5-3-21(34)4-6-22/h2-10,13,16-17,19,36H,11-12,14-15,18H2,1H3,(H,39,41)(H,40,42)

HIDE SMILES / InChI
Molecular Formula C33H29F2N5O4S
Molecular Weight 629.676
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: The description was created based on several sources, including https://encrypted.google.com/patents/WO2009026717A1 | https://clinicaltrials.gov/ct2/show/NCT03015740 | https://clinicaltrials.gov/ct2/show/NCT02978859

MG-516 (Sitravatinib) is a receptor tyrosine kinase (RTK) inhibitor shown in preclinical models to inhibit a closely related spectrum of RTKs including MET, AXL, MER, and members of the VEGFR, PDGFR, DDR2, TRK and Eph families. Broad-spectrum inhibition of multiple RTK signaling pathways by MGCD516 both in vitro and in vivo results in superior activity compared to imatinib and crizotinib. Clinical trials with MGCD516 is currently undergoing.

Originator

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 1.0 nM [IC50]
Inhibitor
8297
 1.5 nM [IC50]
Inhibitor
8297
 0.5 nM [IC50]
Inhibitor
8297
 2.0 nM [IC50]
Inhibitor
8297
 2.0 nM [IC50]
Mast/stem cell growth factor receptor Kit
5
Target ID: P10721
Gene ID: 3815.0
Gene Symbol: KIT
Target Organism: Homo sapiens (Human)
Inhibitor
8297
 6.0 nM [IC50]
Hepatocyte growth factor receptor
54
Target ID: P08581
Gene ID: 4233.0
Gene Symbol: MET
Target Organism: Homo sapiens (Human)
Inhibitor
8297
 20.0 nM [IC50]
Ephrin type-A receptor 3
2
Target ID: P29320
Gene ID: 2042.0
Gene Symbol: EPHA3
Target Organism: Homo sapiens (Human)
Inhibitor
8297
 1.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase I
428
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
21 ng/mL
OTHER
https://www.mirati.com/wp-content/uploads/Mirati-516-003-SITC-2019-Final-Slides-web.pdf
120 mg single, oral
dose: 120 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SITRAVATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
72.5 ng/mL
OTHER
https://www.mirati.com/wp-content/uploads/Mirati-516-003-SITC-2019-Final-Slides-web.pdf
120 mg 1 times / day steady-state, oral
dose: 120 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
SITRAVATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
200 mg 1 times / day multiple, oral (unknown)
Highest studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
https://www.mirati.com/wp-content/uploads/20160603_A-First-in-Human-Phase-1-Study-of-Receptor-Tyrosine-Kinase-RTK-Inhibitor-MGCD516-in-Patients-with-Advanced-Solid-Tumors.pdf
unhealthy
n = 3
Health Status: unhealthy
Condition: Advanced Solid Tumors
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources:
https://www.mirati.com/wp-content/uploads/20160603_A-First-in-Human-Phase-1-Study-of-Receptor-Tyrosine-Kinase-RTK-Inhibitor-MGCD516-in-Patients-with-Advanced-Solid-Tumors.pdf
DLT: Mucositis, Neuropathy...
Dose limiting toxicities:
Mucositis (grade 2, 1 pt)
Neuropathy (grade 2, 1 pt)
Fatigue (grade 2, 1 pt)
Sources:
https://www.mirati.com/wp-content/uploads/20160603_A-First-in-Human-Phase-1-Study-of-Receptor-Tyrosine-Kinase-RTK-Inhibitor-MGCD516-in-Patients-with-Advanced-Solid-Tumors.pdf
80 mg 1 times / day multiple, oral
Studied dose
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources:
https://www.mirati.com/wp-content/uploads/20160603_A-First-in-Human-Phase-1-Study-of-Receptor-Tyrosine-Kinase-RTK-Inhibitor-MGCD516-in-Patients-with-Advanced-Solid-Tumors.pdf
unhealthy
n = 6
Health Status: unhealthy
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
https://www.mirati.com/wp-content/uploads/20160603_A-First-in-Human-Phase-1-Study-of-Receptor-Tyrosine-Kinase-RTK-Inhibitor-MGCD516-in-Patients-with-Advanced-Solid-Tumors.pdf
DLT: Palmar-plantar erythrodysesthesia...
Dose limiting toxicities:
Palmar-plantar erythrodysesthesia (grade 3, 1 pt)
Sources:
https://www.mirati.com/wp-content/uploads/20160603_A-First-in-Human-Phase-1-Study-of-Receptor-Tyrosine-Kinase-RTK-Inhibitor-MGCD516-in-Patients-with-Advanced-Solid-Tumors.pdf
AEs

AEs

AESignificanceDosePopulation
Fatigue grade 2, 1 pt
DLT
200 mg 1 times / day multiple, oral (unknown)
Highest studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
https://www.mirati.com/wp-content/uploads/20160603_A-First-in-Human-Phase-1-Study-of-Receptor-Tyrosine-Kinase-RTK-Inhibitor-MGCD516-in-Patients-with-Advanced-Solid-Tumors.pdf
unhealthy
n = 3
Health Status: unhealthy
Condition: Advanced Solid Tumors
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources:
https://www.mirati.com/wp-content/uploads/20160603_A-First-in-Human-Phase-1-Study-of-Receptor-Tyrosine-Kinase-RTK-Inhibitor-MGCD516-in-Patients-with-Advanced-Solid-Tumors.pdf
Mucositis grade 2, 1 pt
DLT
200 mg 1 times / day multiple, oral (unknown)
Highest studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
https://www.mirati.com/wp-content/uploads/20160603_A-First-in-Human-Phase-1-Study-of-Receptor-Tyrosine-Kinase-RTK-Inhibitor-MGCD516-in-Patients-with-Advanced-Solid-Tumors.pdf
unhealthy
n = 3
Health Status: unhealthy
Condition: Advanced Solid Tumors
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources:
https://www.mirati.com/wp-content/uploads/20160603_A-First-in-Human-Phase-1-Study-of-Receptor-Tyrosine-Kinase-RTK-Inhibitor-MGCD516-in-Patients-with-Advanced-Solid-Tumors.pdf
Neuropathy grade 2, 1 pt
DLT
200 mg 1 times / day multiple, oral (unknown)
Highest studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
https://www.mirati.com/wp-content/uploads/20160603_A-First-in-Human-Phase-1-Study-of-Receptor-Tyrosine-Kinase-RTK-Inhibitor-MGCD516-in-Patients-with-Advanced-Solid-Tumors.pdf
unhealthy
n = 3
Health Status: unhealthy
Condition: Advanced Solid Tumors
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources:
https://www.mirati.com/wp-content/uploads/20160603_A-First-in-Human-Phase-1-Study-of-Receptor-Tyrosine-Kinase-RTK-Inhibitor-MGCD516-in-Patients-with-Advanced-Solid-Tumors.pdf
Palmar-plantar erythrodysesthesia grade 3, 1 pt
DLT
80 mg 1 times / day multiple, oral
Studied dose
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources:
https://www.mirati.com/wp-content/uploads/20160603_A-First-in-Human-Phase-1-Study-of-Receptor-Tyrosine-Kinase-RTK-Inhibitor-MGCD516-in-Patients-with-Advanced-Solid-Tumors.pdf
unhealthy
n = 6
Health Status: unhealthy
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
https://www.mirati.com/wp-content/uploads/20160603_A-First-in-Human-Phase-1-Study-of-Receptor-Tyrosine-Kinase-RTK-Inhibitor-MGCD516-in-Patients-with-Advanced-Solid-Tumors.pdf
PubMed

PubMed

TitleDatePubMed
Patents

Patents

US2009264440
2
US2009286984
4
US2013310564
4
US8389541
2
US8569503
4
US8846927
2
WO2009026717
2

Sample Use Guides

In Vivo Use Guide
MGCD516 administered at 150 mg daily, in continuous 21 day cycles
Route of Administration: Oral
In Vitro Use Guide
MGCD516 (sitravatinib) treatment was able to inhibit proliferation of LS141 and DDLS cell lines significantly better than pazopanib especially at 1000 nM concentration (p<0.0005) suggesting better pathway inhibition by MGCD516.
Substance Class Chemical
Created
by admin
on Sat Dec 16 10:07:46 UTC 2023
Edited
by admin
on Sat Dec 16 10:07:46 UTC 2023
Record UNII
CWG62Q1VTB
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SITRAVATINIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
SITRAVATINIB [USAN]
Common Name English
MGCD-516
Code English
Sitravatinib [WHO-DD]
Common Name English
MG-516
Code English
MG-91516
Code English
sitravatinib [INN]
Common Name English
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)-
Systematic Name English
MGCD516
Code English
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
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C1967
Created by admin on Sat Dec 16 10:07:46 UTC 2023 , Edited by admin on Sat Dec 16 10:07:46 UTC 2023
NCI_THESAURUS C1742
Created by admin on Sat Dec 16 10:07:46 UTC 2023 , Edited by admin on Sat Dec 16 10:07:46 UTC 2023
NCI_THESAURUS C129825
Created by admin on Sat Dec 16 10:07:46 UTC 2023 , Edited by admin on Sat Dec 16 10:07:46 UTC 2023
Code System Code Type Description
FDA UNII
CWG62Q1VTB
Created by admin on Sat Dec 16 10:07:46 UTC 2023 , Edited by admin on Sat Dec 16 10:07:46 UTC 2023
PRIMARY
CAS
1123837-84-2
Created by admin on Sat Dec 16 10:07:46 UTC 2023 , Edited by admin on Sat Dec 16 10:07:46 UTC 2023
PRIMARY
EPA CompTox
DTXSID801100124
Created by admin on Sat Dec 16 10:07:46 UTC 2023 , Edited by admin on Sat Dec 16 10:07:46 UTC 2023
PRIMARY
MANUFACTURER PRODUCT INFORMATION
SITRAVATINIB
Created by admin on Sat Dec 16 10:07:46 UTC 2023 , Edited by admin on Sat Dec 16 10:07:46 UTC 2023
PRIMARY MedKoo CAT NO: 206510; CAS NO: 1123837-84-2; Description: Sitravatinib, also known as MGCD516 or MG516, is a novel small molecule inhibitor targeting multiple RTKs involved in driving sarcoma cell growth. MGCD516 treatment resulted in significant blockade of phosphorylation of potential driver RTKs and induced potent anti-proliferative effects in vitro. MGCD516 treatment of tumor xenografts in vivo resulted in significant suppression of tumor growth. (last updated: 12/28/2015).
NCI_THESAURUS
C117734
Created by admin on Sat Dec 16 10:07:46 UTC 2023 , Edited by admin on Sat Dec 16 10:07:46 UTC 2023
PRIMARY
INN
10216
Created by admin on Sat Dec 16 10:07:46 UTC 2023 , Edited by admin on Sat Dec 16 10:07:46 UTC 2023
PRIMARY
WIKIPEDIA
Sitravatinib
Created by admin on Sat Dec 16 10:07:46 UTC 2023 , Edited by admin on Sat Dec 16 10:07:46 UTC 2023
PRIMARY
DRUG BANK
DB15036
Created by admin on Sat Dec 16 10:07:46 UTC 2023 , Edited by admin on Sat Dec 16 10:07:46 UTC 2023
PRIMARY
PUBCHEM
25212148
Created by admin on Sat Dec 16 10:07:46 UTC 2023 , Edited by admin on Sat Dec 16 10:07:46 UTC 2023
PRIMARY
USAN
DE-140
Created by admin on Sat Dec 16 10:07:46 UTC 2023 , Edited by admin on Sat Dec 16 10:07:46 UTC 2023
PRIMARY
SMS_ID
100000172780
Created by admin on Sat Dec 16 10:07:46 UTC 2023 , Edited by admin on Sat Dec 16 10:07:46 UTC 2023
PRIMARY
Related Record Type Details
Structure of SITRAVATINIB MALATE
SALT/SOLVATE -> PARENT
TYROSINE-PROTEIN KINASE RECEPTOR TYRO3
TARGET -> INHIBITOR
TYROSINE-PROTEIN KINASE MER
TARGET -> INHIBITOR
MAST/STEM CELL GROWTH FACTOR RECEPTOR KIT
TARGET -> INHIBITOR
TYROSINE-PROTEIN KINASE RECEPTOR UFO
TARGET -> INHIBITOR
VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 2
TARGET -> INHIBITOR
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> INHIBITOR
Inhibits the ABCB1 efflux pump by inhibiting the hydrolysis of ATP
Related Record Type Details
Structure of SITRAVATINIB
ACTIVE MOIETY
Originator: MethylGene; Developer: Mirati Therapeutics; Class: Antineoplastic, Small molecule Mechanism of Action: Axl receptor tyrosine kinase inhibitor, Eph family receptor antagonist, Platelet-derived growth factor receptor antagonist, Proto oncogene protein c met inhibitor, Proto oncogene protein c ret inhibitor, Proto oncogene protein c-kit inhibitor, Proto-oncogene protein c-mer inhibitor, Receptor protein-tyrosine kinase antagonist, RON protein inhibitor, TIE 2 receptor antagonist, Tropomyosin-related kinase antagonist, Vascular endothelial growth factor receptor 3 antagonist, Vascular endothelial growth factor receptor-1 antagonist, Vascular endothelial growth factor receptor-2 antagonist; New Molecular Entity: Yes; Highest Development Phase: Phase I for Solid tumours; Most Recent Events: 06 Jun 2016 Adverse events, pharmacokinetics, pharmacodynamics and efficacy data from a phase I trial in Solid tumour released by Mirati Therapeutics (3187888, 9197140), 30 Sep 2015 Interim adverse events and PK data from a phase I/Ib trial in solid tumours presented at the European Cancer Congress (ECC-2015), 04 Sep 2014 Mirati Therapeutics initiates dosing in a phase I trial of Sitravatinib in Solid tumours (advanced disease)
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