Sunitinib free base (SU-11248)

Alias: SU11248; SU 11248; SU011248; SU-11248; sunitinib; trade name: Sutent.
Cat No.:V0497 Purity: ≥98%
Sunitinib (formerly also known as SU11248; trade name: Sutent) is a potent, orally bioavailable and multi-targeted RTK (receptor tyrosine kinase) inhibitor with potential antitumor activity.
Sunitinib free base (SU-11248) Chemical Structure CAS No.: 557795-19-4
Product category: VEGFR
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
250mg
500mg
1g
2g
Other Sizes

Other Forms of Sunitinib free base (SU-11248):

  • Sunitinib Malate (SU-11248 Malate)
  • Sunitinib D10
  • Sunitinib-d4 (Sunitinib d4)
Official Supplier of:
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Sunitinib (formerly also known as SU11248; trade name: Sutent) is a potent, orally bioavailable and multi-targeted RTK (receptor tyrosine kinase) inhibitor with potential antitumor activity. In cell-free assays, it inhibits c-Kit in addition to VEGFR2 (Flk-1) and PDGFRβ, with IC50s of 80 nM and 2 nM, respectively. In 2006, the US FDA approved sunitinib for the treatment of gastrointestinal stromal tumors that were resistant to imatinib and renal cell carcinoma. Sunitinib inhibits angiogenesis and cell proliferation by blocking the tyrosine kinase activities of platelet-derived growth factor receptor b (PDGFRb), c-kit, and vascular endothelial growth factor receptor 2 (VEGFR2).

Biological Activity I Assay Protocols (From Reference)
Targets
PDGFRβ (IC50 = 2 nM); VEGFR2 (IC50 = 80 nM); FLT3; c-Kit
ln Vitro
Sunitinib inhibits FLT-3 and Kit with considerable potency.[1] With a Ki of 9 nM and 8 nM, respectively, sunitinib is a strong ATP-competitive inhibitor of VEGFR2 (Flk1) and PDGFRβ. It provides >10-fold greater selectivity for VEGFR2 and PDGFR than FGFR-1, EGFR, Cdk2, Met, IGFR-1, Abl, and src. With IC50 values of 10 nM and 10 nM, respectively, sunitinib inhibits the phosphorylation of VEGFR2 in response to VEGF and PDGFRβ in response to PDGF in serum-starved NIH-3T3 cells expressing VEGFR2 or PDGFRβ. Sunitinib has an IC50 of 40 nM for VEGF-induced proliferation of serum-starved HUVECs and an IC50 of 39 nM and 69 nM for PDGF-induced proliferation of NIH-3T3 cells overexpressing PDGFRβ or PDGFRβ, respectively.[2] With an IC50 of 250 nM, 50 nM, and 30 nM, respectively, sunitinib inhibits the phosphorylation of wild-type FLT3, FLT3-ITD, and FLT3-Asp835. With IC50 values of 8 nM and 14 nM, respectively, sunitinib suppresses the growth of MV4;11 and OC1-AML5 cells and, in a dose-dependent fashion, triggers apoptosis.[3]
ln 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. This is consistent with the significant and selective inhibition of VEGFR2 or PDGFR phosphorylation and signaling in vivo. Six out of eight mice receiving 80 mg/kg/day of sunitinib for 21 days experience complete tumor regression, and 110 days after the end of the treatment, there is no regrowth of the tumor.Tumors that do not completely regress after the first round of treatment can still be successfully treated with sunitinib in a second round. Tumor MVD significantly decreases with sunitinib treatment, with SF763T glioma tumors reduced by approximately 40%. Tumor size remains unchanged, but luciferase-expressing PC-3M xenografts treated with SU11248 completely inhibits further tumor growth.[2] Treatment with sunitinib (20 mg/kg/day) increases survival in the FLT3-ITD bone marrow engraftment model and significantly suppresses the growth subcutaneous MV4;11 (FLT3-ITD) xenografts.[3]
Enzyme Assay
Sunitinib's IC50 values against PDGFRβ and VEGFR2 (Flk-1) are ascertained by employing glutathione S-transferasefusion proteins that encompass the entire RTK cytoplasmic domain. In order to measure the trans-phosphorylation activity of VEGFR2 (Flk-1) and PDGFRβ, biochemical tyrosine kinase assays are carried out in 96-well microtiter plates that have been precoated (20 μg/well in PBS) and incubated with the peptide substrate poly-Glu,Tyr (4:1) for an entire night at 4 °C. Adding 1-5% (w/v) BSA to PBS blocks excess protein binding sites. The cells of insects infected with baculovirus produce purified GST-fusion proteins. The microtiter wells are then filled with GST-VEGFR2 and GST-PDGFRβ in a 2 × concentration kinase dilution buffer that contains 40 μM NaVO4, 50 mM NaCl, 100 mM HEPES, and 0.02% (w/v) BSA. 50 ng/mL is the final enzyme concentration for GST-VEGFR2 or GST-PDGFRβ. To create a range of inhibitor concentrations suitable for every enzyme, 25 μL of diluted Sunitinib is then added to each reaction well. A solution of MnCl2 is mixed with varying concentrations of ATP to start the kinase reaction. The final concentration of MnCl2 is 10 mM, and the final ATP concentrations span the Km for the enzyme. After allowing the plates to sit at room temperature for five to fifteen minutes, the reaction is halted by adding EDTA. After that, TBST is used to wash the plates three times. After adding rabbit polyclonal antiphosphotyrosine antisera at a 1:10,000 dilution to the wells in TBST containing 0.025% (w/v) nonfat dry milk, 0.5% (w/v) BSA, and 100 μM NaVO4, the wells are incubated at 37 °C for one hour. After three TBST washes, the plates are inoculated with goat anti-rabbit antisera conjugated with horseradish peroxidase (1:10,000 dilution in TBST). The plates are cleaned three times with TBST after an hour of incubation at 37 °C. Once 2,2′-azino-di-[3-ethylbenzthiazoline sulfonate] has been added as substrate, the amount of phosphotyrosine in each well is quantified.
Cell Assay
The cells are starved for an entire night in a medium containing 0.1% FBS before FL (50 ng/mL; FLT3-WT cells only) and sunitinib are added. After 48 hours of culture, proliferation is assessed using trypan blue cell viability assays or the Alamar Blue assay. Apoptosis is quantified using Western blotting 24 hours after Sunitinib addition in order to identify caspase-3 levels or poly (ADP-ribose) polymerase (PARP) cleavage.
Animal Protocol
Mice: The mice used are female nu/nu (8–12 weeks old, 25 grams). In short, on day 0, mice receive a subcutaneous injection of 3-5×106 tumor cells into the hind flank region. After tumors reach the indicated average size, mice bearing tumors are treated daily orally with carboxymethyl cellulose suspension or as a citrate buffered (pH 3.5) solution containing sunitinib. Tumor growth is assessed using tumor volume measurements taken twice a week. When tumors in animals receiving vehicle treatment reach an average size of 1000 mm3 or are determined to negatively impact the animals' quality of life, studies are usually stopped.
Rats: The Wistar rats are adult males weighing between 325 and 349 g. In two drug studies, the efficacy of the time-lapse imaging method in assessing the anti-angiogenic effects of a particular drug treatment is verified. First, mesenteric windows are taken from adult male Wistar rats, and the tissues are cultured for three days in two different experimental groups: 1) 10% serum (n = 8 tissues from 4 rats), and 2) 10% serum + Sunitinib (5 μM; n=8 tissues from 4 rats).
References

[1]. J Med Chem . 2003 Mar 27;46(7):1116-9.

[2]. Clin Cancer Res . 2003 Jan;9(1):327-37.

[3]. Blood . 2003 May 1;101(9):3597-605.

[4]. Mol Cancer Ther . 2003 Oct;2(10):1011-21.

[5]. Blood . 2004 Dec 15;104(13):4202-9.

[6]. Mol Cancer Ther . 2006 Oct;5(10):2522-30.

[7]. EMBO J . 2011 Mar 2;30(5):894-905.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C22H27FN4O2
Molecular Weight
398.47
Exact Mass
398.21
Elemental Analysis
C, 66.31; H, 6.83; F, 4.77; N, 14.06; O, 8.03
CAS #
557795-19-4
Related CAS #
Sunitinib Malate;341031-54-7;Sunitinib-d10;1126721-82-1;Sunitinib-d4;1126721-79-6
Appearance
Yellow solid powder
SMILES
CCN(CC)CCNC(=O)C1=C(NC(=C1C)/C=C\2/C3=C(C=CC(=C3)F)NC2=O)C
InChi Key
WINHZLLDWRZWRT-ATVHPVEESA-N
InChi Code
InChI=1S/C22H27FN4O2/c1-5-27(6-2)10-9-24-22(29)20-13(3)19(25-14(20)4)12-17-16-11-15(23)7-8-18(16)26-21(17)28/h7-8,11-12,25H,5-6,9-10H2,1-4H3,(H,24,29)(H,26,28)/b17-12-
Chemical Name
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide
Synonyms
SU11248; SU 11248; SU011248; SU-11248; sunitinib; trade name: Sutent.
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~25 mg/mL (~62.7 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In Vivo)
5% DMSO+corn oil: 7mg/mL
 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.5096 mL 12.5480 mL 25.0960 mL
5 mM 0.5019 mL 2.5096 mL 5.0192 mL
10 mM 0.2510 mL 1.2548 mL 2.5096 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

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Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02811861 Active
Recruiting
Drug: Lenvatinib
Drug: Sunitinib
Renal Cell Carcinoma Eisai Inc. October 13, 2016 Phase 3
NCT01582204 Active
Recruiting
Drug: 124IcG250 Renal Cancer Memorial Sloan Kettering Cancer
Center
April 2012 Not Applicable
NCT03141177 Active
Recruiting
Drug: Sunitinib
Drug: Cabozantinib
Renal Cell Carcinoma Bristol-Myers Squibb August 22, 2017 Phase 3
NCT01621568 Active
Recruiting
Drug: Sunitinib Thymoma
Thymus Neoplasms
National Cancer Institute
(NCI)
May 15, 2012 Phase 2
NCT03878524 Active
Recruiting
Drug: Abemaciclib
Drug: Sunitinib
Primary Myelofibrosis
Anemia
OHSU Knight Cancer Institute April 1, 2020 Phase 1
Biological Data
  • Sunitinib (free base)

  • Sunitinib (free base)
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