Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C17H15N9 |
Molecular Weight | 345.3613 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
C[C@H](N1N=NC2=NC=C(N=C12)C3=CN(C)N=C3)C4=CN5C=CN=C5C=C4
InChI
InChIKey=XYDNMOZJKOGZLS-NSHDSACASA-N
InChI=1S/C17H15N9/c1-11(12-3-4-15-18-5-6-25(15)10-12)26-17-16(22-23-26)19-8-14(21-17)13-7-20-24(2)9-13/h3-11H,1-2H3/t11-/m0/s1
DescriptionSources: http://www.hmplglobal.com/en/volitinibhmpl-504/Curator's Comment: description was created based on several sources, including
http://www.chi-med.com/initiation-of-azd6094-hmpl-504volitinib-global-phase-ii-study-in-papillary-renal-cell-carcinoma-2/
Sources: http://www.hmplglobal.com/en/volitinibhmpl-504/
Curator's Comment: description was created based on several sources, including
http://www.chi-med.com/initiation-of-azd6094-hmpl-504volitinib-global-phase-ii-study-in-papillary-renal-cell-carcinoma-2/
Savolitinib (AZD6094, HMPL-504) has been demonstrated to inhibit the growth of tumors in a series of preclinical disease models, selectively for those tumors with aberrant c-Met signaling. Phase I dose escalation studies were initiated in Australia and China in 2012 and 2013 respectively. Savolitinib has demonstrated good safety and tolerability and favorable pharmacokinetic properties in late stage cancer patients, and has shown encouraging anti-tumor activity in several tumor-types, in particular for metastatic Papillary Renal Cell Cancer (PRCC). Phase II, study designed to evaluate the efficacy and safety of savolitinib in patients with locally advanced or metastatic PRCC. Approximately 20 centers in the United States, Canada, and Europe will participate in the study. The primary objective of this study is to assess the anti-tumor activity in patients with PRCC as measured by overall response rate according to Response Evaluation Criteria in Solid Tumours (“RECIST”). The secondary objectives for this study are to: assess the progression free survival and duration of response in patients with PRCC according to RECIST; assess the safety and tolerability in the treatment of patients with PRCC; characterize the pharmacokinetics and pharmacodynamics of savolitinib and metabolites following administration to steady state after multiple dosing when given orally.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3717 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25148209 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
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OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
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Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
likely [IC50 100 uM] | ||||
likely [IC50 100 uM] | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/ |
no | |||
no | ||||
no | ||||
no | ||||
no | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/ |
weak [EC50 >3.6 uM] | |||
weak [IC50 35 uM] | ||||
weak [IC50 50 uM] | ||||
weak [IC50 >30 uM] | ||||
weak [IC50 >50 uM] | ||||
weak [IC50 >50 uM] | ||||
weak [IC50 >50 uM] | ||||
weak [IC50 >50 uM] | ||||
weak [IC50 >50 uM] | ||||
weak [IC50 >50 uM] | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/ |
weak | |||
yes [IC50 11 uM] | ||||
yes [IC50 11 uM] | ||||
yes [IC50 13 uM] | ||||
yes [IC50 16 uM] | ||||
yes [IC50 20 uM] | ||||
yes [IC50 22 uM] | ||||
yes [IC50 24 uM] | ||||
yes [IC50 27 uM] | ||||
yes [IC50 4.7 uM] | ||||
yes [IC50 6.4 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | ||||
major | ||||
major | ||||
major | ||||
major | ||||
minor | yes (co-administration study) Comment: Rifampicin decreased Cmax and AUC by 37% and 49%. Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/ |
|||
minor | yes (co-administration study) Comment: Rifampicin decrease Cmax and AUC by 55% and 61%. |
|||
no | ||||
yes | no (co-administration study) Comment: Itraconazole increased Cmax and AUC by 5.2% and 8.4%. Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/ |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT02127710
600 mg by mouth once daily
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27472392
Curator's Comment: In vitro, savolitinib inhibits MET phosphorylation with nanomolar potency, which correlates with blockade of PI3K/AKT and MAPK signaling as well as MYC down-regulation.
Unknown
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NCI_THESAURUS |
C129825
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NCI_THESAURUS |
C1967
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NCI_THESAURUS |
C1742
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C104732
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EF-02
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SUB181945
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1313725-88-0
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DTXSID801111016
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68289010
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DB12048
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100000168519
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9935
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2A2DA6857R
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CHEMBL3545336
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Savolitinib
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ACTIVE MOIETY