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MedKoo Cat#: 100790 | Name: Sunitinib malate
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Sunitinib, also known as SU11248, is the orally bioavailable malate salt of an indolinone-based tyrosine kinase inhibitor with potential antineoplastic activity. Sunitinib was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) on January 26, 2006. Sunitinib blocks the tyrosine kinase activities of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor b (PDGFRb), and c-kit, thereby inhibiting angiogenesis and cell proliferation.

Chemical Structure

Sunitinib malate
Sunitinib malate
CAS#341031-54-7 (malate)

Theoretical Analysis

MedKoo Cat#: 100790

Name: Sunitinib malate

CAS#: 341031-54-7 (malate)

Chemical Formula: C26H33FN4O7

Exact Mass: 0.0000

Molecular Weight: 532.56

Elemental Analysis: C, 58.64; H, 6.25; F, 3.57; N, 10.52; O, 21.03

Price and Availability

Size Price Availability Quantity
100mg USD 150.00 Ready to ship
500mg USD 250.00 Ready to ship
1g USD 350.00 Ready to ship
2g USD 550.00 Ready to ship
5g USD 950.00 Ready to ship
10g USD 1,450.00 Ready to ship
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Related CAS #
341031-54-7 (malate) 557795-19-4 (free base) 342641-94-5 1126641-10-8 (maleate) 1221149-36-5 (acetate) 1327155-72-5 (HCl) 1275588-72-1 (mesylate) 1332306-95-2 (oxalate)
Synonym
SU11248; SU-11248; SU 11248; SU011248; Sunitinib malate; Sutent.
IUPAC/Chemical Name
(Z)-N-(2-(diethylamino)ethyl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide malate
InChi Key
LBWFXVZLPYTWQI-HBPAQXCTSA-N
InChi Code
InChI=1S/C22H27FN4O2.C4H6O5/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;5-2(4(8)9)1-3(6)7/h7-8,11-12,25H,5-6,9-10H2,1-4H3,(H,24,29)(H,26,28);2,5H,1H2,(H,6,7)(H,8,9)/b17-12-;
SMILES Code
O=C(C1=C(C)NC(/C=C2C(NC3=C\2C=C(F)C=C3)=O)=C1C)NCCN(CC)CC.OC(CC(O)=O)C(O)=O
Appearance
Yellow solid powder
Purity
>99% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Sunitinib malate is the orally bioavailable malate salt of an indolinone-based tyrosine kinase inhibitor with potential antineoplastic activity. Sunitinib blocks the tyrosine kinase activities of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor b (PDGFRb), and c-kit, thereby inhibiting angiogenesis and cell proliferation. This agent also inhibits the phosphorylation of Fms-related tyrosine kinase 3 (FLT3), another receptor tyrosine kinase expressed by some leukemic cells.    Sunitinib malate is a yellow to orange powder with a pKa of 8.95. The solubility of sunitinib malate in aqueous media over the range pH 1.2 to pH 6.8 is in excess of 25 mg/mL. The log of the distribution coefficient (octanol/water) at pH 7 is 5.2. SUTENT (sunitinib malate) capsules are supplied as printed hard shell capsules containing sunitinib malate equivalent to 12.5 mg, 25 mg or 50 mg of sunitinib together with mannitol, croscarmellose sodium, povidone (K-25) and magnesium stearate as inactive  ngredients. The orange gelatin capsule shells contain titanium dioxide, and red iron oxide. The caramel gelatin capsule shells also contain yellow iron oxide and black iron oxide. The printing ink contains shellac, propylene glycol, sodium hydroxide, povidone and titanium dioxide.   Sunitinib (marketed as Sutent by Pfizer, and previously known as SU11248) is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) on January 26, 2006. Sunitinib was the first cancer drug simultaneously approved for two different indications. Sunitinib has become a standard of care for both of these cancers, and is currently being studied for the treatment of many others.     According to http://en.wikipedia.org/wiki/Sunitinib, Sunitinib is a standard of care in the first-line treatment of metastatic RCC, other therapeutic options in this setting are sorafenib (Nexavar), temsirolimus (Torisel) and interleukin-2 (Proleukin). RCC is generally resistant to chemotherapy or radiation. Prior to RTKs, metastatic disease could only be treated with the cytokines interferon alpha (IFNα) or Interleukin 2 (IL-2). However, these agents demonstrated low rates of efficacy (5%-20%). In two separate Phase II studies, sunitinib demonstrated consistent response rates of approximately 40% in patients who had already failed cytokine therapy. Although these were Phase II studies, these results were impressive enough for the FDA to approve sunitinib for first-line use even before Phase III data were available. The results of the Phase III study, published in the New England Journal of Medicine in 2007, proved that sunitinib offers superior efficacy compared with IFNα. Progression-free survival (primary endpoint) was more than doubled: 11 months for sunitinib compared with 5 months for IFNα (P<.000001). The benefit for sunitinib was significant across all major patient subgroups, including those with a poor prognosis at baseline. Secondary endpoints also favored sunitinib. 28% of sunitinib patients had significant tumor shrinkage (objective response) compared with only 5% of patients who received IFNα (P<.001). Although overall survival data are not yet mature, there is a clear trend toward improved survival with sunitinib. Patients receiving sunitinib also reported a significantly better quality of life than those treated with IFNα (P<.001). According to http://en.wikipedia.org/wiki/Sunitinib, Sunitinib is a standard of care in the first-line treatment of metastatic RCC, other therapeutic options in this setting are sorafenib (Nexavar), temsirolimus (Torisel) and interleukin-2 (Proleukin). RCC is generally resistant to chemotherapy or radiation. Prior to RTKs, metastatic disease could only be treated with the cytokines interferon alpha (IFNα) or Interleukin 2 (IL-2). However, these agents demonstrated low rates of efficacy (5%-20%). In two separate Phase II studies, sunitinib demonstrated consistent response rates of approximately 40% in patients who had already failed cytokine therapy. Although these were Phase II studies, these results were impressive enough for the FDA to approve sunitinib for first-line use even before Phase III data were available. The results of the Phase III study, published in the New England Journal of Medicine in 2007, proved that sunitinib offers superior efficacy compared with IFNα. Progression-free survival (primary endpoint) was more than doubled: 11 months for sunitinib compared with 5 months for IFNα (P<.000001). The benefit for sunitinib was significant across all major patient subgroups, including those with a poor prognosis at baseline. Secondary endpoints also favored sunitinib. 28% of sunitinib patients had significant tumor shrinkage (objective response) compared with only 5% of patients who received IFNα (P<.001). Although overall survival data are not yet mature, there is a clear trend toward improved survival with sunitinib. Patients receiving sunitinib also reported a significantly better quality of life than those treated with IFNα (P<.001).
Biological target:
Sunitinib Malate is a receptor tyrosine kinase inhibitor with IC50s of 80 nM and 2 nM for VEGFR2 and PDGFRβ, respectively.
In vitro activity:
In order to determine the impact of sunitinib on ectopic endometrial cells, ectopic and normal endometrial cells were treated with sunitinib at appointed concentrations of 0, 1, 2, 4, 8, and 16 uM for 48 hours. The MTT assay revealed that the half maximal inhibitory concentration (IC50) of normal endometrial cells to sunitinib (IC50 = 7.9 μM) was significantly higher, when compared to ectopic endometrial cells (IC50 = 3.32 μM), suggesting that sunitinib has no effect on the normal endometrium within the therapeutic concentration range, since it is on the ectopic endometrium in vitro (Figure 2A). Then, it was measured that sunitinib reduced the cell apoptosis by nuclear-fluorescence staining. These results show that the number of apoptotic cells in the ectopic endometrial group (100x) increased with the increase in sunitinib concentration (Figure 2B). Furthermore, in order to confirm the results above, the cell apoptosis was determined by flow cytometry. The cell apoptosis rate (FITC + plus FITC+/PI+) in ectopic endometrial cells was 51.9%±8.3% and 78.8% ± 3.2% at a sunitinib concentration of 4 μM and 8 μM, respectively, and both were significantly higher than that in normal endometrial cells, with 0.2% ± 1.2% (vs ectopic endometrial cells, P < .0001, t = 26.89) and 68.1% ± 2.1% (vs ectopic endometrial cells, P = .025, t = 3.49), respectively (Figure 2C). These results demonstrate that sunitinib can affect the cell proliferation and apoptosis of ectopic endometrial cells in a dose-dependent manner. Reference: J Clin Lab Anal. 2020 Nov;34(11):e23482. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676178/
In vivo activity:
Mice were treated orally with sunitinib (7.5 mg/kg/day) for 2 weeks. Sunitinib did not affect body weight, but increased plasma ALT activity 6-fold. Protein and mRNA expression of several subunits of mitochondrial enzyme complexes were decreased in mitochondria from sunitinib-treated mice. Protein expression of PGC-1α, citrate synthase activity and mtDNA copy number were all decreased in livers of sunitinib-treated mice, indicating impaired mitochondrial proliferation. Caspase 3 activation and TUNEL-positive hepatocytes were increased in livers of sunitinib-treated mice, indicating hepatocyte apoptosis. In conclusion, sunitinib caused concentration-dependent toxicity in isolated mitochondria at concentrations reached in livers in vivo and inhibited hepatic mitochondrial proliferation. Daily mitochondrial insults and impaired mitochondrial proliferation most likely explain hepatocellular injury observed in mice treated with sunitinib. Reference: Toxicology. 2018 Nov 1;409:13-23. https://www.sciencedirect.com/science/article/abs/pii/S0300483X18301574?via%3Dihub
Solvent mg/mL mM
Solubility
DMF 1.0 1.88
DMSO 28.3 53.20
DMSO:PBS (pH 7.2) (1:3) 0.3 0.47
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 532.56 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Li J, Abudula M, Fan X, Wang F, Chen Y, Liu L. Sunitinib induces primary ectopic endometrial cell apoptosis through up-regulation of STAT1 in vitro. J Clin Lab Anal. 2020 Nov;34(11):e23482. doi: 10.1002/jcla.23482. Epub 2020 Aug 5. PMID: 32761670; PMCID: PMC7676178. 2. Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, Schreck RE, Abrams TJ, Ngai TJ, Lee LB, Murray LJ, Carver J, Chan E, Moss KG, Haznedar JO, Sukbuntherng J, Blake RA, Sun L, Tang C, Miller T, Shirazian S, McMahon G, Cherrington JM. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res. 2003 Jan;9(1):327-37. PMID: 12538485. 3. Paech F, Abegg VF, Duthaler U, Terracciano L, Bouitbir J, Krähenbühl S. Sunitinib induces hepatocyte mitochondrial damage and apoptosis in mice. Toxicology. 2018 Nov 1;409:13-23. doi: 10.1016/j.tox.2018.07.009. Epub 2018 Jul 18. PMID: 30031043.
In vitro protocol:
1. Li J, Abudula M, Fan X, Wang F, Chen Y, Liu L. Sunitinib induces primary ectopic endometrial cell apoptosis through up-regulation of STAT1 in vitro. J Clin Lab Anal. 2020 Nov;34(11):e23482. doi: 10.1002/jcla.23482. Epub 2020 Aug 5. PMID: 32761670; PMCID: PMC7676178. 2. Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, Schreck RE, Abrams TJ, Ngai TJ, Lee LB, Murray LJ, Carver J, Chan E, Moss KG, Haznedar JO, Sukbuntherng J, Blake RA, Sun L, Tang C, Miller T, Shirazian S, McMahon G, Cherrington JM. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res. 2003 Jan;9(1):327-37. PMID: 12538485.
In vivo protocol:
1. Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, Schreck RE, Abrams TJ, Ngai TJ, Lee LB, Murray LJ, Carver J, Chan E, Moss KG, Haznedar JO, Sukbuntherng J, Blake RA, Sun L, Tang C, Miller T, Shirazian S, McMahon G, Cherrington JM. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res. 2003 Jan;9(1):327-37. PMID: 12538485. 2. Paech F, Abegg VF, Duthaler U, Terracciano L, Bouitbir J, Krähenbühl S. Sunitinib induces hepatocyte mitochondrial damage and apoptosis in mice. Toxicology. 2018 Nov 1;409:13-23. doi: 10.1016/j.tox.2018.07.009. Epub 2018 Jul 18. PMID: 30031043.
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