Name: Apatinib (YN968D1) mesylate
Brand: Selleck Chemicals
SKU: S2221
Rating: 5 (22 reviews)

Apatinib mesylate (YN968D1, Rivoceranib) is a potent inhibitor of the VEGF signaling pathway with IC50 values of 1 nM, 13 nM, 429 nM and 530 nM for VEGFR-2, Ret (c-Ret), c-Kit and c-Src, respectively. Apatinib mesylate induces both autophagy and apoptosis.

Apatinib (YN968D1) mesylate Chemical Structure

CAS: 1218779-75-9

Selleck's Apatinib (YN968D1) mesylate has been cited by 22 publications

Purity & Quality Control

Batch: Purity: 99.74%

99.74

Apatinib (YN968D1) mesylate Related Products

Related Targets	VEGFR1 VEGFR2 VEGFR3	Click to Expand
Related Compound Libraries	Kinase Inhibitor Library Tyrosine Kinase Inhibitor Library PI3K/Akt Inhibitor Library Cell Cycle compound library Angiogenesis Related compound Library	Click to Expand

Signaling Pathway

VEGFR Signaling Pathway

Choose Selective VEGFR Inhibitors

Biological Activity

Description

Apatinib mesylate (YN968D1, Rivoceranib) is a potent inhibitor of the VEGF signaling pathway with IC50 values of 1 nM, 13 nM, 429 nM and 530 nM for VEGFR-2, Ret (c-Ret), c-Kit and c-Src, respectively. Apatinib mesylate induces both autophagy and apoptosis.

Features

Good anti-tumor effects for gastric and colorectal cancer compared with sorafenib and sunitinib.

Targets

VEGFR2 ^[1] (Cell-free assay)	RET ^[1] (Cell-free assay)
1 nM	13 nM

In vitro
In vitro	Apatinib (YN968D1) is a novel, orally bioavailable, selective inhibitor with potential antiangiogenic and antineoplastic activities. Apatinib selectively binds to and inhibits VEGFR2. Apatinib can also potently suppress the activities of Ret, c-kit and c-src with IC50 of 0.013 μM, 0.429 μM and 0.53 μM, respectively. Apatinib inhibits cellular phosphorylation of VEGFR-2, c-kit and PDGFRβ. Apatinib significantly inhibits proliferation stimulated by 20 ng/mL VEGF (IC50 = 0.17μM). Apatinib effectively inhibits proliferation, migration and tube formation of human umbilical vein endothelial cells induced by FBS, and blocked the budding of rat aortic ring. ^[1] Apatinib reverses ABCB1- and ABCG2-mediated MDR by inhibiting their transport function, but not by blocking the AKT or ERK1/2 pathway or downregulating ABCB1 or ABCG2 expression. Apatinib significantly potentiates the cytotoxicity of established ABCB1 and ABCG2 substrates and increased the accumulation of DOX and Rho 123 in ABCB1- or ABCG2-overexpressing cells. Furthermore, apatinib significantly inhibited the photoaffinity labeling of both ABCB1 and ABCG2 with [¹²⁵I]iodoarylazidoprazosin in a concentration-dependent manner. ^[2]
Kinase Assay	Enzyme-linked immunosorbent assay
Kinase Assay	A poly(glu, ala, tyr) 6:3:1 random copolymer is used as a tyrosine containing substrate solution. The substrate is stored as a 1 mg/mL stock in PBS at −20 °C and diluted 1 in 500 with PBS in order to coat 96 well plates (100 μL/well). Plates are coated on the day prior to assay, sealed with adhesive seals, and stored overnight at 4 °C. On the day of the assay, the substrate solution is discarded and the assay plate wells are washed once with PBST (PBS containing 0.05% v/v Tween 20) and once with Hepes buffer (50 mM, pH 7.4).Test compounds are diluted with 10% dimethylsulfoxide (DMSO) de-ionized water and 25 μL volumes transferred to wells in the washed assay plates. Manganese chloride solution (40 mM) containing 8 μM ATP is then added (25 μL) to all test wells. Control and blank wells, containing compound diluent and manganese chloride solution with and without ATP, respectively, are also included to determine the dynamic range of the assay. Freshly diluted enzyme (50 μL) is added to each well, and the plates incubated at room temperature for 20 min. The liquid is then discarded and the wells are washed twice with PBST. Mouse IgG anti-phosphotyrosine antibody diluted 1:6000 with PBST containing 0.5% (w/v) bovine serum albumin (BSA) is added (100 μL/well), and the plates incubated for 1h at room temperature before discarding the liquid and washing the wells twice with PBST. Horseradish peroxidase (HRP)-linked sheep anti-mouse Ig antibody diluted 1:500 with PBST containing 0.5% (w/v) BSA, is then added (100 μL/well) and the plates incubated for a further 1 h at room temperature before discarding the liquid and washing the wells twice with PBST. A 1 mg/mL solution of 2,2‘-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid is freshly prepared in 50 mM phosphate-citrate buffer (pH5.0) containing 0.03% (w/v) sodium perborate, and 100 μL added to each well. Plates are then incubated for 20−60 min at room temperature until the optical density value of control wells measured at 405 nm is approximately 1.0. IC50 values for compound enzyme inhibition are interpolated using Microcal Origin following subtraction of blank values.
Cell Research	Cell lines	HUVEC
	Concentrations	~25 μM
	Incubation Time	72 h
	Method	The HUVEC are seeded into 96-well plates. After 24 h of incubation, cells are exposed to the test agents (vehicle as control) together with 20 ng/mL VEGF or 20% FBS for another 72 h. After fixation with 10% trichloroacetic acid, the cells are stained with 0.4% sulforhodamine B for 30 min at 37 °C and then washed with 1% acetic acid. Tris is added to dissolve the complex, and the optical density is measured at 520 n
Experimental Result Images	Methods	Biomarkers	Images	PMID
	Western blot	p-VEGFR2 / VEGFR2 / p-ERK / ERK PI3K / p-PI3K / mTOR / p-mTOR / AKT / p-AKT Beclin 1 / Atg7 / p62 / LC3-I / LC3-II		29490645
	Growth inhibition assay	Cell viability		29490645

In Vivo
In vivo	Apatinib inhibits the growth of a broad range of human tumor xenografts in a significant dose-dependent manner. ^[1] Apatinib reverses ABCB1-mediated MDR in the nude mouse xenograft model. ^[2] Apatinib significantly enhances the antitumor activity of doxorubicin in nude mice bearing K562/ADR xenografts. ^[3]
Animal Research	Animal Models	Ls174t, HCT 116, SGC-7901, HT-29, A549, NCI-H460 xenografted BALB/cA nude mice
	Dosages	50, 100, 200 mg/kg
	Administration	p.o.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT05839197	Recruiting	Macrotrabecular Massive Hepatocellular Carcinoma	Wan-Guang Zhang\|Tongji Hospital	May 5 2023	Phase 2
NCT05742750	Not yet recruiting	Locally Advanced Biliary Tract Cancer\|Metastatic Biliary Tract Cancer	Sun Yat-sen University\|Jiangsu Hengrui Pharmaceutical Co. Ltd.	March 1 2023	Phase 1\|Phase 2
NCT05287360	Completed	Healthy	Elevar Therapeutics	December 30 2021	Phase 1
NCT04517357	Unknown status	Relapsed Ovarian Cancer	Jiangsu HengRui Medicine Co. Ltd.	October 16 2020	Phase 2
NCT03743428	Suspended	Colorectal Neoplasms	Shenzhen People''s Hospital	October 22 2020	Not Applicable

References

Chemical Information & Solubility

Molecular Weight	493.58	Formula	C₂₅H₂₇N₅O₄S
CAS No.	1218779-75-9	SDF	Download Apatinib (YN968D1) mesylate SDF
Smiles	C[S](O)(=O)=O.O=C(NC1=CC=C(C=C1)C2(CCCC2)C#N)C3=CC=CN=C3NCC4=CC=NC=C4
Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 99 mg/mL ( (200.57 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

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Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

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

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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.
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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

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Frequently Asked Questions

Question 1:
How to reconstitute the compound S2221 for in vivo studies?

Answer:
We suggest the vehicle 0.5% CMC. In vehicle 0.5% CMC, the compound is not fully dissolved. However, the mixture is a stable suspension and can be used for oral gavage feeding.

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