Home Protein Tyrosine Kinase c-Met inhibitor Savolitinib (AZD6094) For research use only.

Savolitinib (AZD6094)

Synonyms: HMPL-504, Volitinib

Savolitinib (Volitinib, AZD6094, HMPL-504) is a novel, potent, and selective MET inhibitor currently in clinical development in various indications, including PRCC. The IC50 values of this compound for c-Met and p-Met are 5 nM and 3 nM, respectively. It shows exquisite selectivity for c-Met over 274 kinase.

Savolitinib (AZD6094) Chemical Structure

Savolitinib (AZD6094) Chemical Structure

CAS No. 1313725-88-0

Purity & Quality Control

Savolitinib (AZD6094) Related Products

Signaling Pathway

c-Met Signaling Pathways

c-Met Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
NCI-H441 Function assay 1 h Inhibition of c-Met autophosphorylation in human NCI-H441 cells for 1 hr by ELISA, IC50=0.003 μM 25148209
NCI-H441 Proliferation assay 72 h Antiproliferative activity against human NCI-H441 cells assessed as HGF-induced proliferation after 72 hrs by MTT assay, IC50=0.006 μM 25148209
Click to View More Cell Line Experimental Data

Biological Activity

Description Savolitinib (Volitinib, AZD6094, HMPL-504) is a novel, potent, and selective MET inhibitor currently in clinical development in various indications, including PRCC. The IC50 values of this compound for c-Met and p-Met are 5 nM and 3 nM, respectively. It shows exquisite selectivity for c-Met over 274 kinase.
Targets
p-Met [1]
(Cell-free assay)		 c-Met [1]
(Cell-free assay)
3 nM 5 nM
In vitro
In vitro

Volitinib has exquisite kinase selectivity and excellent potency[1]. Volitinib displays a highly selective profile across a gastric cell line panel, potently inhibiting cell growth only in those lines with dysregulated cMET (EC50 values 0.6 nM/L-12.5 nM/L)[2]. Volitinib has high membrane permeability without efflux transport across Caco-2 cell monolayer and exhibits negligible P-gp inhibition (IC50 > 17 μM). Volitinib shows no significant reversible or mechanism-based CYP inhibition in human liver microsomes, and no induction of CYP1A2 and CYP3A4 in human hepatocytes[3].
Cell Research Cell lines NCI-H441 cells
Concentrations --
Incubation Time 1 h
Method

NCI-H441 cells are plated at a density of 15,000 cells/well in RPMI-1640 medium with 10% FBS in 96-well plates. After incubation overnight, cells are then treated with serially diluted test compounds at 37 ℃ for 1 h. Then the medium is removed, and cells are lysed in 100 μL/well lysis buffer.The plates containing cell lysate are kept at -80℃ overnight. The next day, the plates are thawed on ice, mixed gently. 25 μL/well of lysates are added into the assay plates pre-coated with anti-p-Met antibody to detect p-c-Met signal. p-c-Met level is determined at 450 nm and 570 nm.
Experimental Result Images Methods Biomarkers Images PMID
Western blot pMET / MET / pAKT / AKT / pERK / ERK 27472392
Growth inhibition assay Cell viability 27472392
In Vivo
In vivo

In a mouse pharmacokinetic study (male ICR mice), the clearance of the compound is 4.28 L/(h·kg) and the half-time is 1.7 h. Despite its moderate oral bioavailability (F = 27.2%), the overall plasma exposure is much higher. Volitinib demonstrates dose-dependent tumor growth inhibition in a U87MG subcutaneous xenograft model[1]. Its treatment leads to pharmacodynamic modulation of c-MET signaling and potent tumor stasis in 3/3 cMET-dysregulated gastric cancer patient-derived tumor xenograft models, but has negligible activity in a gastric cancer control model[2]. Volitinib has moderate plasma protein binding rate (60%∼70% in rat, dog, and human; 40% in mouse; 80% in monkey) and exhibits wide distribution to different organs in rat, with high exposures in liver and kidney, very low in brain, spinal cord and testis compared to the plasma level. In PK studies in mouse, rat and dog, Volitinib shows the rapid oral absorption (Tmax<2.5 h) with high exposures and the acceptable bioavailability at 27.2%, 42.6% and 86.3%, respectively. The in vivo clearance (CL) is 11.0, 11.8 and 3.5 mL/min/kg in mouse, rat and dog, respectively, revealing a low extraction ratio. The volume of distribution in steady state (Vss) is 0.4, 1.4 and 1.4 L/kg in those species, respectively, indicating a moderate to low distribution pattern. Volitinib also displays linear pharmacokinetics (PK) in the dose ranges of 1 to 25 mg/kg in rat and 2 to 10 mg/kg in dog. Food hardly affects its PK profile in dog. In contrast, volitinib in monkey shows a notably high extraction ratio (CL=17.2 mL/min/kg) consistent with the in vitro metabolism result. Considering the rapid absorption of volitinib (Tmax=1.9 h) and moderately low distribution (Vss=0.7 L/kg), the poor oral bioavailability (1.9%) of volitinib in monkey is considered to be the result of excessive first-pass extraction. Overall, volitinib exhibits favorable preclinical PK/ADME properties[3].
Animal Research Animal Models Female athymic mice
Dosages 1.0, 2.5 and 10.0 mg/kg (oral); 2.5 mg/kg (i.v.)
Administration oral administration/i.v.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05888207 Completed
Healthy Male Subjects
AstraZeneca|Parexel
 June 2 2023 Phase 1
NCT05043090 Recruiting
Papillary Renal Cell Carcinoma
AstraZeneca
 October 28 2021 Phase 3
NCT04606771 Active not recruiting
Non-Small Cell Lung Cancer
AstraZeneca
 September 28 2020 Phase 2

Chemical Information & Solubility

Molecular Weight 345.36 Formula

C17H15N9
CAS No. 1313725-88-0 SDF Download Savolitinib (AZD6094) SDF
Smiles CC(C1=CN2C=CN=C2C=C1)N3C4=NC(=CN=C4N=N3)C5=CN(N=C5)C
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 69 mg/mL ( (199.79 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.


In vivo Formulation Calculator

Preparing Stock Solutions

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.
Tags: buy Savolitinib (AZD6094) | Savolitinib (AZD6094) supplier | purchase Savolitinib (AZD6094) | Savolitinib (AZD6094) cost | Savolitinib (AZD6094) manufacturer | order Savolitinib (AZD6094) | Savolitinib (AZD6094) distributor