SAVOLITINIB

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

Structure Search

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

HIDE SMILES / InChI

Molecular Formula	C17H15N9
Molecular Weight	345.3613
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
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
Hepatocyte growth factor receptor 54 Target ID: CHEMBL3717 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25148209	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Papillary renal cell cancer 1 Sources: https://clinicaltrials.gov/ct2/show/NCT02127710	Primary		Phase II 1132	Unknown Approved Use Unknown
Advanced gastric adenocarcinoma 3 Sources: https://clinicaltrials.gov/ct2/show/NCT02447380	Primary		Phase II 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781 substrate 1737	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1478 CYP3A4/5 278 CYP2A6 707 CYP1A2 1524 CYP2C8 911 CYP2E1 882 CYP2B6 810	P-gp 1537 FMO 35 UGT1A4 347 CYP1A2 1054 UGT2B15 203 CYP2C19 991 CYP 270 AO 16	CYP1A2 701 CYP2B6 547

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	likely [IC50 100 uM]
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	likely [IC50 100 uM]
CYP1A2 1692	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	no
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	no
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	no
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	no	M2 2
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	no
CYP3A4 1925	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak [EC50 >3.6 uM]
CYP3A4/5 335	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak [IC50 35 uM]	M3 2
CYP3A4/5 335	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak [IC50 50 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak [IC50 >30 uM]	M2 2
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak [IC50 >50 uM]	M3 2
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak [IC50 >50 uM]	M2 2
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak [IC50 >50 uM]	M3 2
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak [IC50 >50 uM]	M3 2
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak [IC50 >50 uM]	M2 2
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak [IC50 >50 uM]	M3 2
CYP2B6 1001	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	yes [IC50 11 uM]	M3 2
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	yes [IC50 11 uM]	M3 2
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	yes [IC50 13 uM]	M2 2
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	yes [IC50 16 uM]
CYP3A4/5 335	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	yes [IC50 20 uM]	M2 2
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	yes [IC50 22 uM]	M2 2
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	yes [IC50 24 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	yes [IC50 27 uM]	M2 2
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	yes [IC50 4.7 uM]
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	yes [IC50 6.4 uM]	M2 2

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
AO 16	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	major
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	major
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	major
UGT1A4 347	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	major	M2 9
UGT2B15 203	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	major	M2 9
CYP 270	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	minor	M2 9	yes (co-administration study) Comment: Rifampicin decreased Cmax and AUC by 37% and 49%. Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/
CYP3A4 1737	substrate 3367	minor		yes (co-administration study) Comment: Rifampicin decrease Cmax and AUC by 55% and 61%.
FMO 35	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31132401/	no
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	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
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/33733338/
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/33733338/		M2 1

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P009D0V	https://www.1pchem.com/search?query=1P009D0V
AChemBlock	P50944	http://www.achemblock.com/catalogsearch/result/?q=P50944
AstaTech	42573	http://astatechinc.com/CPSResult.php?CRNO=42573
BLD Pharm	BD630116	http://www.bldpharm.com/search/Search.html?keyword=BD630116
Chem Scene	CS-4062	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-4062
ChemShuttle	153871	https://www.chemshuttle.com/catalogsearch/result/?q=153871
Excenen	EX-A845	http://www.excenen.com/searchresultlist.php?id=EX-A845
KeyOrganics	AS-35250	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-35250
Lab Network	LN01342548	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01342548
MedChem Express	HY-15959	https://www.medchemexpress.com/search.html?q=HY-15959&ft=&fa=&fp=
MolPort	MolPort-046-417-113	https://www.molport.com/shop/molecule-link/MolPort-046-417-113
MuseChem	I001202	https://www.musechem.com/product/I001202.html
eMolecules	271384498	https://orderbb.emolecules.com/search/#?query=271384498
eMolecules	302080517	https://orderbb.emolecules.com/search/#?query=302080517
eMolecules	53745148	https://orderbb.emolecules.com/search/#?query=53745148
mcule	MCULE-2245459005	https://mcule.com/MCULE-2245459005/

PubMed

Title	Date	PubMed
The MET Inhibitor AZD6094 (Savolitinib, HMPL-504) Induces Regression in Papillary Renal Cell Carcinoma Patient-Derived Xenograft Models.	2015 Jun 15	25779944
Acquired savolitinib resistance in non-small cell lung cancer arises via multiple mechanisms that converge on MET-independent mTOR and MYC activation.	2016 Sep 6	27472392

Patents

Sample Use Guides

In Vivo Use Guide

600 mg by mouth once daily

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:47:02 UTC 2023` Edited by `admin` on `Sat Dec 16 08:47:02 UTC 2023`
Record UNII	2A2DA6857R
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

SAVOLITINIB

Official Name

English

VOLITINIB

Common Name

English

HMPL-504

Code

English

1-((S)-1-(IMIDAZO(1,2-A)PYRIDIN-6-YL)ETHYL)-6-(1-METHYL-1H-PYRAZOL-4-YL)-1H-(1,2,3)-TRIAZOLO(4,5-B)PYRAZINE

Systematic Name

English

AZD6094

Code

English

SAVOLITINIB [USAN]

Common Name

English

1H-1,2,3-TRIAZOLO(4,5-B)PYRAZINE, 1-((1S)-1-IMIDAZO(1,2-A)PYRIDIN-6-YLETHYL)-6-(1-METHYL-1H-PYRAZOL-4-YL)-

Systematic Name

English

Savolitinib [WHO-DD]

Common Name

English

savolitinib [INN]

Common Name

English

AZD-6094

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C129825