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
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)
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/26675259Curator'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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26675259
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
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL4954 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26675259 |
1.0 nM [IC50] | ||
Target ID: CHEMBL4895 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26675259 |
1.5 nM [IC50] | ||
Target ID: CHEMBL5122 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26675259 |
0.5 nM [IC50] | ||
Target ID: CHEMBL5331 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26675259 |
2.0 nM [IC50] | ||
Target ID: CHEMBL1955 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26675259 |
2.0 nM [IC50] | ||
Target ID: P10721 Gene ID: 3815.0 Gene Symbol: KIT Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26675259 |
6.0 nM [IC50] | ||
Target ID: P08581 Gene ID: 4233.0 Gene Symbol: MET Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26675259 |
20.0 nM [IC50] | ||
Target ID: P29320 Gene ID: 2042.0 Gene Symbol: EPHA3 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26675259 |
1.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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: |
unhealthy n = 3 Health Status: unhealthy Condition: Advanced Solid Tumors Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: |
DLT: Mucositis, Neuropathy... Dose limiting toxicities: Mucositis (grade 2, 1 pt) Sources: Neuropathy (grade 2, 1 pt) Fatigue (grade 2, 1 pt) |
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: |
unhealthy n = 6 Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: |
DLT: Palmar-plantar erythrodysesthesia... Dose limiting toxicities: Palmar-plantar erythrodysesthesia (grade 3, 1 pt) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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: |
unhealthy n = 3 Health Status: unhealthy Condition: Advanced Solid Tumors Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: |
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: |
unhealthy n = 3 Health Status: unhealthy Condition: Advanced Solid Tumors Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: |
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: |
unhealthy n = 3 Health Status: unhealthy Condition: Advanced Solid Tumors Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: |
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: |
unhealthy n = 6 Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT02978859
MGCD516 administered at 150 mg daily, in continuous 21 day cycles
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26675259
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.
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C1967
Created by
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NCI_THESAURUS |
C1742
Created by
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NCI_THESAURUS |
C129825
Created by
admin on Sat Dec 16 10:07:46 GMT 2023 , Edited by admin on Sat Dec 16 10:07:46 GMT 2023
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Code System | Code | Type | Description | ||
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CWG62Q1VTB
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1123837-84-2
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DTXSID801100124
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SITRAVATINIB
Created by
admin on Sat Dec 16 10:07:46 GMT 2023 , Edited by admin on Sat Dec 16 10:07:46 GMT 2023
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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). | ||
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C117734
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10216
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Sitravatinib
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DB15036
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25212148
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DE-140
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100000172780
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)