SAVOLITINIB

Investigational

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 56 Target ID: CHEMBL3717 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25148209	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Papillary renal cell cancer 1 Sources: https://clinicaltrials.gov/ct2/show/NCT02127710	Primary		Phase II 1147	Unknown Approved Use Unknown
Advanced gastric adenocarcinoma 3 Sources: https://clinicaltrials.gov/ct2/show/NCT02447380	Primary		Phase II 1147	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087 substrate 1946	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 2057 CYP3A4/5 296 CYP2A6 879 CYP1A2 2153 CYP2C8 1057 CYP2E1 1060 CYP2B6 926	P-gp 2052 FMO 34 UGT1A4 399 CYP1A2 1197 UGT2B15 236 CYP2C19 1119 CYP 303	CYP1A2 832 CYP2B6 669

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	likely [IC50 100 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	likely [IC50 100 uM]
CYP1A2 2333	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	no
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	no
CYP2A6 911	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	no
CYP2A6 911	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	no	M2 2
CYP2B6 1160	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	no
CYP3A4 2633	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak [EC50 >3.6 uM]
CYP3A4/5 357	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak [IC50 35 uM]	M3 2
CYP3A4/5 357	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak [IC50 50 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak [IC50 >30 uM]	M2 2
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak [IC50 >50 uM]	M3 2
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak [IC50 >50 uM]	M2 2
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak [IC50 >50 uM]	M3 2
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak [IC50 >50 uM]	M3 2
CYP2E1 1146	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak [IC50 >50 uM]	M2 2
CYP2E1 1146	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak [IC50 >50 uM]	M3 2
CYP2B6 1160	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	weak
CYP2C8 1117	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	yes [IC50 11 uM]	M3 2
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	yes [IC50 11 uM]	M3 2
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	yes [IC50 13 uM]	M2 2
CYP2C8 1117	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	yes [IC50 16 uM]
CYP3A4/5 357	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	yes [IC50 20 uM]	M2 2
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	yes [IC50 22 uM]	M2 2
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	yes [IC50 24 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	yes [IC50 27 uM]	M2 2
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	yes [IC50 4.7 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	yes [IC50 6.4 uM]	M2 2

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	major
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	major
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	major	M2 12
UGT2B15 236	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	major	M2 12
CYP 303	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	minor	M2 12	yes (co-administration study) Comment: Rifampicin decreased Cmax and AUC by 37% and 49%. Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/	minor		yes (co-administration study) Comment: Rifampicin decrease Cmax and AUC by 55% and 61%. Sources: https://pubmed.ncbi.nlm.nih.gov/34322894/
FMO 34	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31132401/	no
P-gp 2052	substrate 4014 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 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/33733338/
hERG 2263	inhibitor 2237 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
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
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
mcule	MCULE-2245459005	https://mcule.com/MCULE-2245459005/
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

PubMed

Title	Date	PubMed
Acquired savolitinib resistance in non-small cell lung cancer arises via multiple mechanisms that converge on MET-independent mTOR and MYC activation.	2016-09-06	27472392
The MET Inhibitor AZD6094 (Savolitinib, HMPL-504) Induces Regression in Papillary Renal Cell Carcinoma Patient-Derived Xenograft Models.	2015-06-15	25779944

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 `Mon Mar 31 22:18:40 GMT 2025` Edited by `admin` on `Mon Mar 31 22:18:40 GMT 2025`
Record UNII	2A2DA6857R
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

VOLITINIB

Preferred Name

English

SAVOLITINIB

Official 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