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Orantinib (SU6668) PDGFR inhibitor

Name: Orantinib (SU6668)
Brand: Selleck Chemicals
SKU: S1470
Availability: InStock
Rating: 5 (21 reviews)

Cat.No.S1470

Orantinib (SU6668) has greatest potency against PDGFR autophosphorylation with K_i of 8 nM in a cell-free assay, but also strongly inhibits Flk-1 and FGFR1 trans-phosphorylation. It shows little activity against IGF-1R, Met, Src, Lck, Zap70, Abl and CDK2, and does not inhibit EGFR. This compound is in Phase 3.

Chemical Structure

Molecular Weight: 310.35

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Quality Control

Batch: Purity: 99.73%

99.73

Related Targets	EGFR VEGFR FGFR c-Met Src MEK CSF-1R FLT3 HER2 c-Kit
Other PDGFR Inhibitors	CP-673451 Crenolanib Tyrphostin AG 1296 Trapidil PP121 AZD2932 Sennoside B Tyrphostin AG1433 AG 1295 N-(p-Coumaroyl) Serotonin

Solubility

In vitro
Batch:

DMSO : 62 mg/mL (199.77 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	10%DMSO 1 40%PEG300 2 5%Tween80 3 45%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	7.500mg/ml (24.17mM)	Taking the 1 mL working solution as an example, add 100 μL of 75 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 450 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

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

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

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.

Chemical Information, Storage & Stability

Molecular Weight	310.35	Formula	C₁₈H₁₈N₂O₃	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	252916-29-3	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	TSU-68			Smiles	CC1=C(NC(=C1CCC(=O)O)C)C=C2C3=CC=CC=C3NC2=O

Mechanism of Action

Targets/IC₅₀/Ki	PDGFRβ (Cell-free assay) 8 nM(Ki)
In vitro	Orantinib (SU6668) is a competitive inhibitor, with regard to ATP, to Flk-1/KDR trans-phosphorylation, FGFR1 trans-phosphorylation, and PDGFRβ kinases autophosphorylation. It (0.03-10 μM) inhibits tyrosine phosphorylation of KDR in VEGF stimulated HUVECs. This compound also inhibits PDGF-stimulated PDGFRβ tyrosine phosphorylation in NIH-3T3 cells overexpressing PDGFRβ at a minimum concentration of 0.03-0.1 μM. It inhibits acidic FGF-induced phosphorylation of the FGFR1 substrate 2 at 10 μM and higher. However, TSU-68 (up to 100 μM) has no effect on EGF-stimulated EGFR tyrosine phosphorylation in NIH-3T3 cells overexpressing EGFR. It inhibits VEGF-driven and FGF-driven mitogenesis of HUVECs with mean IC50 of 0.34 μM and 9.6 μM, respectively. In human myeloid leukemia MO7E cells, this compound inhibits the tyrosine autophosphorylation of stem cell factor (SCF) receptor, c-kit, with IC50 of 0.1-1 μM, as well as ERK1/2 phosphorylation, a signaling event downstream of c-kit activation. It also inhibits SCF-induced proliferation of MO7E cells with IC50 of 0.29 μM, and induces apoptosis.
Kinase Assay	trans-Phosphorylation Reactions
Kinase Assay	Tyrosine kinase assays to quantitate the trans-phosphorylation activity of Flk-1 and FGFR1 are performed in 96-well microtiter plates precoated (20 μg/well in PBS; incubated overnight at 4 °C) with the peptide substrate poly-Glu,Tyr (4:1). Excess protein binding sites are blocked with 1-5% (w/v) BSA in PBS. Purified GST-FGFR1 (kinase domain) or GST-Flk-1 (cytoplasmic domain) fusion proteins are then added to the microtiter wells in 2 × concentration kinase dilution buffer consisting of 100 mM HEPES, 50 mM NaCl, 40 μM NaVO₄, and 0.02% (w/v) BSA. The final enzyme concentration for GST-Flk-1 and GST-FGFR1 is 50 ng/mL. Orantinib (SU6668) is dissolved in DMSO at 100× the final required concentration and diluted 1:25 in H₂O. Twenty-five μL of diluted this compound are subsequently added to each reaction well. The kinase reaction is initiated by the addition of different concentrations of ATP in a solution of MnCl2 so that the final ATP concentrations spanned the Km for the enzyme, and the final concentration of MnCl₂ is 10 mM. The plates are incubated for 5-15 min at room temperature before stopping the reaction with the addition of EDTA. The plates are then washed three times with TBST. Rabbit polyclonal antiphosphotyrosine antisera are added to the wells at a 1: 10000 dilution in TBST containing 0.5% (w/v) BSA, 0.025% (w/v) nonfat dry milk, and 100 μM NaVO₄ and incubated for 1 hour at 37 °C. The plates are then washed three times with TBST, followed by the addition of goat anti-rabbit antisera conjugated with HRP. The plates are incubated for 1 hour at 37 °C and then washed three times with TBST. The amount of phosphotyrosine in each well is quantitated after the addition of 2,2
In vivo	Orantinib (SU6668) induces tumor growth inhibition against a broad range of tumor types in xenograft models in athymic mice, including A375, Colo205, H460, Calu-6, C6, SF763T, and SKOV3TP5 cells at doses of 75-200 mg/kg. This compound (75 mg/kg) also suppresses tumor angiogenesis of C6 glioma xenografts. In a tumor model of HT29 human colon carcinoma, it (200 mg/kg) decreases the average vessel permeability and average fractional plasma volume in the tumor rim and core. TSU-68 promotes abnormal stromal development at the periphery of carcinomas. In a rabbit VX2 liver tumor model, it (200 mg/kg) augments the effect of chemotherapeutic infusion.
References	[1] https://pubmed.ncbi.nlm.nih.gov/10945623/ [2] https://pubmed.ncbi.nlm.nih.gov/11222388/ [3] https://pubmed.ncbi.nlm.nih.gov/14760097/ [4] https://pubmed.ncbi.nlm.nih.gov/21184227/

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