Sunitinib

Catalog No.S7781 Batch:S778103

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Technical Data

Formula

C22H27FN4O2
Molecular Weight 398.47 CAS No. 557795-19-4
Solubility (25°C)* In vitro DMSO 35 mg/mL (87.83 mM)
Ethanol 5 mg/mL (12.54 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Sunitinib is a multi-targeted RTK inhibitor targeting VEGFR2 (Flk-1) and PDGFRβ with IC50 of 80 nM and 2 nM, and also inhibits c-Kit. Sunitinib is also a dose-dependent inhibitor of the autophosphorylation activity of IRE1α. Sunitinib induces autophagy and apoptosis.
Targets
FLT3 [1]
(Cell-free assay)		 c-Kit [1]
(Cell-free assay)		 PDGFRβ [1]
(Cell-free assay)		 VEGFR2 [1]
(Cell-free assay)
2 nM 80 nM
In vitro Sunitinib also potently inhibits Kit and FLT-3. [1] Sunitinib is a potent ATP-competitive inhibitor of VEGFR2 (Flk1) and PDGFRβ with Ki of 9 nM and 8 nM, respectively, displaying >10-fold higher selectivity for VEGFR2 and PDGFR than FGFR-1, EGFR, Cdk2, Met, IGFR-1, Abl, and src. In serum-starved NIH-3T3 cells expressing VEGFR2 or PDGFRβ, Sunitinib inhibits VEGF-dependent VEGFR2 phosphorylation and PDGF-dependent PDGFRβ phosphorylation with IC50 of 10 nM and 10 nM, respectively. Sunitinib inhibits VEGF-induced proliferation of serum-starved HUVECs with IC50 of 40 nM, and inhibits PDGF-induced proliferation of NIH-3T3 cells overexpressing PDGFRβ or PDGFRα with IC50 of 39 nM and 69 nM, respectively. [2] Sunitinib inhibits phosphorylation of wild-type FLT3, FLT3-ITD, and FLT3-Asp835 with IC50 of 250 nM, 50 nM, and 30 nM, respectively. Sunitinib inhibits the proliferation of MV4;11 and OC1-AML5 cells with IC50 of 8 nM and 14 nM, respectively, and induces apoptosis in a dose-dependent manner. [3]
In vivo Consistent with the substantial and selective inhibition of VEGFR2 or PDGFR phosphorylation and signaling in vivo, Sunitinib (20-80 mg/kg/day) exhibits broad and potent dose-dependent anti-tumor activity against a variety of tumor xenograft models including HT-29, A431, Colo205, H-460, SF763T, C6, A375, or MDA-MB-435. Sunitinib dosing at 80 mg/kg/day for 21 days leads to complete tumor regression in six of eight mice, without tumor re-growing during a 110-day observation period after the end of treatment. Second round of treatment with Sunitinib remains efficacious against tumors that are not fully regressed during the first round of treatment. Sunitinib treatment results in significant decrease in tumor MVD, with ~40% reduction in SF763T glioma tumors. SU11248 treatment results in a complete inhibition of additional tumor growth of luciferase-expressing PC-3M xenografts, despite no reduction in tumor size. [2] Sunitinib treatment (20 mg/kg/day) dramatically suppresses the growth subcutaneous MV4;11 (FLT3-ITD) xenografts and prolongs survival in the FLT3-ITD bone marrow engraftment model. [3]

Protocol (from reference)

Kinase Assay:

[1]
  • Biochemical Tyrosine Kinase Assays

    IC50 values for Sunitinib against VEGFR2 (Flk-1) and PDGFRβ are determined using glutathione S-transferase fusion proteins containing the complete cytoplasmic domain of the RTK. Biochemical tyrosine kinase assays to quantitate the trans-phosphorylation activity of VEGFR2 (Flk-1) and PDGFRβ 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 the addition of 1-5% (w/v) BSA in PBS. Purified GST-fusion proteins are produced in baculovirus-infected insect cells. GST-VEGFR2 and GST-PDGFRβ 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-VEGFR2 or GST-PDGFRβ is 50 ng/mL. Twenty-five μL of diluted Sunitinib are subsequently added to each reaction well to produce a range of inhibitor concentrations appropriate for each enzyme. 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 minutes 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 1:10,000 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 antirabbit antisera conjugated with horseradish peroxidase (1:10,000 dilution in TBST). 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′-azino-di-[3-ethylbenzthiazoline sulfonate] as substrate.
Cell Assay:

[3]
  • Cell lines

    RS4;11, MV4;11, and OC1-AML5

  • Concentrations

    Dissolved in DMSO, final concentrations ~10 μM

  • Incubation Time

    24 and 48 hours

  • Method

    Cells are starved overnight in medium containing 0.1% FBS prior to addition of Sunitinib and FL (50 ng/mL; FLT3-WT cells only). Proliferation is measured after 48 hours of culture using the Alamar Blue assay or trypan blue cell viability assays. Apoptosis is measured 24 hours after Sunitinib addition by Western blotting to detect cleavage of poly (ADP-ribose) polymerase (PARP) or levels of caspase-3.
Animal Study:

[2]
  • Animal Models

    Female nu/nu mice implanted s.c. with HT-29, A431, Colo205, H-460, SF763T, C6, A375, or MDA-MB-435, and male nu/nu mice bearing luciferase-expressing PC-3M tumors

  • Dosages

    ~80 mg/kg

  • Administration

    Orally once daily

Customer Product Validation

Data from [Surgery, 2012, 152, 1045-50]

Data from [Surgery, 2012, 152, 1045-50]

Data from [Surgery, 2012, 152, 1142-9]

Data from [Surgery, 2012, 152, 1142-9]

Selleck's Sunitinib has been cited by 240 publications

Topical Delivery of Tofacitinib in Dermatology: The Promise of a Novel Therapeutic Class Using Biodegradable Dendritic Polyglycerol Sulfates [ Pharmaceuticals (Basel), 2024, 17(1)77] PubMed: 38256910
Astragaloside IV attenuates sunitinib-associated cardiotoxicity by inhibiting COUP-TFII [ Heliyon, 2024, 10(3):e24779] PubMed: 38314260
BAX activation in mouse retinal ganglion cells occurs in two temporally and mechanistically distinct steps [ Mol Neurodegener, 2023, 18(1):67] PubMed: 37752598
Extracellular Vesicle-Mediated Transfer of LncRNA IGFL2-AS1 Confers Sunitinib Resistance in Renal Cell Carcinoma [ Cancer Res, 2023, 83(1):103-116] PubMed: 36264173
Extracellular Vesicle-Mediated Transfer of LncRNA IGFL2-AS1 Confers Sunitinib Resistance in Renal Cell Carcinoma [ Cancer Res, 2023, 83(1):103-116] PubMed: 36264173
ZDHHC2-Mediated AGK Palmitoylation Activates AKT-mTOR Signaling to Reduce Sunitinib Sensitivity in Renal Cell Carcinoma [ Cancer Res, 2023, 83(12):2034-2051] PubMed: 37078777
A new scaffold-free tumoroid model provides a robust preclinical tool to investigate invasion and drug response in Renal Cell Carcinoma [ Cell Death Dis, 2023, 14(9):622] PubMed: 37736770
Targeting Prohibitins to Inhibit Melanoma Growth and Overcome Resistance to Targeted Therapies [ Cells, 2023, 12(14)1855] PubMed: 37508519
A subset of VEGFR-TKIs activates AMPK in LKB1-mutant lung cancer [ Cancer Sci, 2023, 114(4):1651-1662] PubMed: 36459496
Connexin43 is associated with the progression of clear cell renal carcinoma and is regulated by tangeretin to sygergize with tyrosine kinase inhibitors [ Transl Oncol, 2023, 35:101712] PubMed: 37354638

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