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Details

Stereochemistry ABSOLUTE
Molecular Formula C33H29F2N5O4S.C4H6O5
Molecular Weight 763.764
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SITRAVATINIB MALATE

SMILES

O[C@@H](CC(O)=O)C(O)=O.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=GDLGZWLGDROYHH-WNQIDUERSA-N
InChI=1S/C33H29F2N5O4S.C4H6O5/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;5-2(4(8)9)1-3(6)7/h2-10,13,16-17,19,36H,11-12,14-15,18H2,1H3,(H,39,41)(H,40,42);2,5H,1H2,(H,6,7)(H,8,9)/t;2-/m.0/s1

HIDE SMILES / InChI

Molecular Formula C4H6O5
Molecular Weight 134.0874
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
1.0 nM [IC50]
1.5 nM [IC50]
0.5 nM [IC50]
2.0 nM [IC50]
2.0 nM [IC50]
Target ID: P10721
Gene ID: 3815.0
Gene Symbol: KIT
Target Organism: Homo sapiens (Human)
6.0 nM [IC50]
Target ID: P08581
Gene ID: 4233.0
Gene Symbol: MET
Target Organism: Homo sapiens (Human)
20.0 nM [IC50]
Target ID: P29320
Gene ID: 2042.0
Gene Symbol: EPHA3
Target Organism: Homo sapiens (Human)
1.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
21 ng/mL
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
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
unhealthy
n = 3
DLT: Mucositis, Neuropathy...
80 mg 1 times / day multiple, oral
Studied dose
unhealthy
n = 6
DLT: Palmar-plantar erythrodysesthesia...
AEs

AEs

AESignificanceDosePopulation
Fatigue grade 2, 1 pt
DLT
200 mg 1 times / day multiple, oral (unknown)
Highest studied dose
unhealthy
n = 3
Mucositis grade 2, 1 pt
DLT
200 mg 1 times / day multiple, oral (unknown)
Highest studied dose
unhealthy
n = 3
Neuropathy grade 2, 1 pt
DLT
200 mg 1 times / day multiple, oral (unknown)
Highest studied dose
unhealthy
n = 3
Palmar-plantar erythrodysesthesia grade 3, 1 pt
DLT
80 mg 1 times / day multiple, oral
Studied dose
unhealthy
n = 6
PubMed

PubMed

TitleDatePubMed
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.
2016 Jan 26
Patents

Sample Use Guides

MGCD516 administered at 150 mg daily, in continuous 21 day cycles
Route of Administration: Oral
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 10:07:26 GMT 2023
Edited
by admin
on Sat Dec 16 10:07:26 GMT 2023
Record UNII
ZR2110H6XE
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SITRAVATINIB MALATE
USAN  
Official Name English
MGCD516 MALATE SALT
Code English
SITRAVATINIB L-MALATE
Common Name English
N-(3-FLUORO-4-(2-(5-((2-METHOXYETHYLAMINO) METHYL) PYRIDIN-2-YL) THIENO (3,2-B) PYRIDIN- 7-YLOXY) PHENYL)-N-(4-FLUOROPHENYL) CYCLOPROPANE-1,1-DICARBOXAMIDE , L-MALATE SALT
Systematic Name 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 (2S)-2-HYDROXYBUTANEDIOATE (1:1)
Common Name English
SITRAVATINIB MALATE [USAN]
Common Name English
BUTANEDIOIC ACID, 2-HYDROXY-, (2S)-, COMPD. WITH N-(3-FLUORO-4-((2-(5-(((2-METHOXYETHYL)AMINO)METHYL)-2-PYRIDINYL)THIENO(3,2-B)PYRIDIN-7-YL)OXY)PHENYL)-N'-(4-FLUOROPHENYL)-1,1-CYCLOPROPANEDICARBOXAMIDE (1:1)
Common Name English
MGCD-516 MALATE SALT
Code English
MGCD-516 L-MALATE
Code English
Code System Code Type Description
CAS
2244864-88-6
Created by admin on Sat Dec 16 10:07:26 GMT 2023 , Edited by admin on Sat Dec 16 10:07:26 GMT 2023
PRIMARY
USAN
GH-63
Created by admin on Sat Dec 16 10:07:26 GMT 2023 , Edited by admin on Sat Dec 16 10:07:26 GMT 2023
PRIMARY
PUBCHEM
137796909
Created by admin on Sat Dec 16 10:07:26 GMT 2023 , Edited by admin on Sat Dec 16 10:07:26 GMT 2023
PRIMARY
SMS_ID
300000011143
Created by admin on Sat Dec 16 10:07:26 GMT 2023 , Edited by admin on Sat Dec 16 10:07:26 GMT 2023
PRIMARY
NCI_THESAURUS
C171930
Created by admin on Sat Dec 16 10:07:26 GMT 2023 , Edited by admin on Sat Dec 16 10:07:26 GMT 2023
PRIMARY
FDA UNII
ZR2110H6XE
Created by admin on Sat Dec 16 10:07:26 GMT 2023 , Edited by admin on Sat Dec 16 10:07:26 GMT 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY