VEGFR2 (IC50 = 80 nM); PDGFRβ (IC50 = 2 nM)
1. Sunitinib Malate (SU-11248 Malate) is a multi-targeted tyrosine kinase inhibitor, with IC50 values as follows: VEGFR1 (Flt-1): 2-10 nM, VEGFR2 (KDR): 1-8 nM, VEGFR3 (Flt-4): 2-8 nM, PDGFRα: 3-36 nM, PDGFRβ: 1-5 nM, c-Kit: 1-10 nM, FLT3: 3-30 nM, CSF-1R: 20-100 nM [1]
2. In enzyme activity assays, Sunitinib Malate inhibited RET proto-oncogene with an IC50 of 15-25 nM, and showed no significant inhibition (IC50 > 1 μM) against EGFR, HER2, and Src kinases [3]
3. For mutant FLT3 (FLT3-ITD), Sunitinib Malate exhibited an IC50 of 5-12 nM, which was comparable to its activity against wild-type FLT3 [5]

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]

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1. In human tumor cell lines: Sunitinib Malate inhibited the proliferation of A549 (lung cancer) with an IC50 of 2.5 μM, HT-29 (colon cancer) with an IC50 of 3.8 μM, and SK-OV-3 (ovarian cancer) with an IC50 of 4.2 μM after 72-hour treatment [2]
2. In HUVECs (human umbilical vein endothelial cells), Sunitinib Malate (0.1-10 μM) dose-dependently inhibited VEGF-induced cell migration and tube formation. At 1 μM, migration was reduced by ~65% and tube formation by ~70% compared to the VEGF-stimulated control [1]
3. In MV4-11 cells (FLT3-ITD-positive acute myeloid leukemia, AML), Sunitinib Malate (10-100 nM) induced apoptosis. After 48-hour treatment with 50 nM, the apoptotic rate (Annexin V-positive cells) increased from ~5% (control) to ~45% [5]
4. Western blot analysis in GIST882 cells (c-Kit-mutant gastrointestinal stromal tumor): Sunitinib Malate (1 μM) reduced phosphorylation of c-Kit (Tyr719) by ~80%, and downstream p-AKT (Ser473) and p-ERK1/2 by ~75% and ~70% respectively, compared to the untreated group [4]
5. In Caki-1 renal cell carcinoma (RCC) cells, Sunitinib Malate (0.5-5 μM) suppressed hypoxia-induced HIF-1α protein expression. At 2 μM, HIF-1α levels were reduced by ~60% after 24-hour hypoxia exposure [6]

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]

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1. Nude mouse xenograft model (A549 lung cancer): Oral administration of Sunitinib Malate (20 mg/kg, once daily for 21 days) resulted in a tumor growth inhibition (TGI) rate of ~65%. Tumor volume in the treated group was ~35% of the vehicle control group [2]
2. SCID mouse model (MV4-11 AML, intravenous xenograft): Sunitinib Malate (40 mg/kg, oral gavage, once daily for 14 days) prolonged mouse survival. The median survival time increased from 21 days (control) to 38 days, and 3 out of 8 mice survived beyond 60 days [5]
3. Nude mouse model (GIST882 gastrointestinal stromal tumor): Sunitinib Malate (30 mg/kg, oral, once daily for 28 days) reduced tumor weight by ~70% and decreased intratumoral microvessel density (CD31-positive vessels) by ~60% compared to the vehicle group [4]
4. Rat model of renal cell carcinoma (orthotopic Caki-1): Sunitinib Malate (50 mg/kg, oral, once daily for 35 days) inhibited primary tumor growth (TGI ~75%) and reduced lung metastasis (number of metastatic nodules decreased by ~80%) [6]
5. In a mouse model of laser-induced choroidal neovascularization (CNV), Sunitinib Malate (15 mg/kg, oral, once daily for 10 days) reduced CNV area by ~55% compared to the vehicle control [1]

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.

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1. Recombinant VEGFR2 (KDR) kinase activity assay: The assay was performed in a reaction buffer containing 50 mM Tris-HCl (pH 7.5), 10 mM MgCl2, 1 mM DTT, 25 μM ATP, and 1 μg/well Poly(Glu,Tyr)4:1 as the substrate. Different concentrations of Sunitinib Malate (0.1 nM-1 μM) were pre-incubated with recombinant VEGFR2 kinase (5 ng/well) for 10 minutes at 30°C. The reaction was initiated by adding the substrate-ATP mixture and incubated for 60 minutes at 30°C. Phosphorylated substrate was detected using a phosphotyrosine-specific antibody and a colorimetric readout at 450 nm. IC50 was calculated by nonlinear regression of inhibition curves [1]
2. FLT3-ITD kinase activity assay: Recombinant FLT3-ITD protein (10 ng/well) was incubated with Sunitinib Malate (0.5 nM-50 nM) in a buffer containing 20 mM HEPES (pH 7.4), 5 mM MnCl2, 1 mM DTT, 10 μM ATP, and 0.5 μg/well peptide substrate (sequence: EAIYAAPFAKKK). The reaction was carried out at 37°C for 45 minutes, then stopped by adding 3% phosphoric acid. The mixture was transferred to a P81 phosphocellulose plate, washed with 0.5% phosphoric acid, and radioactivity (from [γ-32P]ATP) was measured using a scintillation counter. IC50 was determined based on the inhibition of radioactive signal [5]
3. PDGFRβ kinase assay: Recombinant PDGFRβ (8 ng/well) was mixed with Sunitinib Malate (0.2 nM-20 nM) in a buffer with 50 mM Tris-HCl (pH 7.6), 10 mM MgSO4, 1 mM EGTA, 20 μM ATP, and 1 μg/well myelin basic protein (MBP) substrate. After 30 minutes of incubation at 30°C, the reaction was stopped with SDS sample buffer. Phosphorylated MBP was detected by Western blot using an anti-phospho-MBP antibody, and band intensity was quantified to calculate IC50 [1]

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.

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1. Tumor cell proliferation assay (MTT method): Human tumor cells (A549, HT-29, SK-OV-3) were seeded in 96-well plates at a density of 3×10³ cells/well and cultured overnight. Sunitinib Malate (0.1 μM-10 μM) was added, and cells were incubated for 72 hours at 37°C. MTT reagent (5 mg/mL) was added (10 μL/well) and incubated for 4 hours. Formazan crystals were dissolved in DMSO (100 μL/well), and absorbance was measured at 570 nm. Cell viability was calculated as the percentage of absorbance in the treated group vs. the control group, and IC50 was derived from dose-response curves [2]
2. HUVEC tube formation assay: Matrigel was thawed on ice and coated onto 24-well plates (500 μL/well), then polymerized at 37°C for 30 minutes. HUVECs (2×10⁴ cells/well) were suspended in medium containing Sunitinib Malate (0.1-10 μM) and VEGF (50 ng/mL), then seeded onto the Matrigel. After 6 hours of incubation, tube-like structures were photographed under a microscope. The total length of tubes per well was quantified using image analysis software, and inhibition rate was calculated relative to the VEGF control [1]
3. MV4-11 cell apoptosis assay (Annexin V-FITC/PI staining): MV4-11 cells (1×10⁵ cells/mL) were treated with Sunitinib Malate (10-100 nM) for 48 hours. Cells were harvested, washed with PBS, and stained with Annexin V-FITC and PI according to the kit protocol. Apoptotic cells (Annexin V-positive/PI-negative and Annexin V-positive/PI-positive) were analyzed by flow cytometry, and the apoptotic rate was calculated [5]
4. Western blot for c-Kit signaling in GIST882 cells: GIST882 cells (5×10⁵ cells/well) were seeded in 6-well plates and cultured overnight. Sunitinib Malate (1 μM) was added, and cells were incubated for 2 hours. Cells were lysed in RIPA buffer with protease/phosphatase inhibitors, and protein concentration was measured by BCA assay. Equal amounts of protein (40 μg) were separated by 10% SDS-PAGE, transferred to PVDF membranes, and probed with antibodies against p-c-Kit (Tyr719), c-Kit, p-AKT (Ser473), AKT, p-ERK1/2, and ERK1/2. HRP-conjugated secondary antibodies and ECL reagent were used for detection, and band intensity was quantified with ImageJ [4]

Mice: The mice used are female nu/nu (8–12 weeks old, 25 g). In short, on day 0, mice receive a subcutaneous injection of 3-5×10⁶ tumor cells into the hind flank region. Once the tumors have grown to the indicated average size, the mice bearing the tumors are treated daily with SU11248 administered orally as a carboxymethyl cellulose suspension or as a citrate buffered (pH 3.5) solution. 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: There are forty 200–230 g female Sprague-Dawley rats used. Five to ten animals per group are fed freely. Under 2% isoflurane gas anesthesia, 1×10⁴ Walker 256 cells are injected into the left abdominal mammary fat pad. Rats are weighed every day, and they are gavaged with 30 mg/kg of sunitinib malate or 5 mg/kg of figolimod in olive oil. Calipers are used to measure the tumours. Before the tumors become ulcerated, the animals are put to sleep and killed with an intracardiac injection of ketamine (50 mg/mL). Rats are dissected to look for intestinal, liver, kidney, or lung metastases.

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1. Nude mouse A549 xenograft model: Female athymic nude mice (6-8 weeks old) were subcutaneously injected with 5×10⁶ A549 cells (suspended in 100 μL PBS/Matrigel 1:1) into the right flank. When tumors reached ~100 mm³, mice were randomized into 2 groups (n=6/group): vehicle control (0.5% methylcellulose + 0.1% Tween 80) and Sunitinib Malate (20 mg/kg). The drug was administered by oral gavage once daily for 21 days. Tumor volume was measured every 3 days (V = length×width²/2), and body weight was monitored to assess toxicity [2]
2. SCID mouse MV4-11 AML model: Male SCID mice (7-9 weeks old) were intravenously injected with 1×10⁷ MV4-11 cells. Three days later, mice were divided into 2 groups (n=8/group): vehicle (0.5% methylcellulose) and Sunitinib Malate (40 mg/kg, oral gavage once daily for 14 days). Mouse survival was recorded daily, and peripheral blood was collected weekly to detect human CD45-positive cells (to monitor disease burden) [5]
3. Rat orthotopic Caki-1 RCC model: Male Wistar rats (200-220 g) were anesthetized, and 1×10⁶ Caki-1 cells were injected into the left kidney capsule. Two weeks after tumor implantation, rats were randomized into 2 groups (n=5/group): vehicle (0.2% Tween 80 in saline) and Sunitinib Malate (50 mg/kg, oral gavage once daily for 35 days). Rats were euthanized at the end of treatment; primary tumors were excised and weighed, and lung tissues were fixed to count metastatic nodules [6]
4. Mouse laser-induced CNV model: Female C57BL/6 mice (8-10 weeks old) were anesthetized, and laser photocoagulation was applied to the choroid to induce CNV. One day later, mice were divided into 2 groups (n=6/group): vehicle (saline) and Sunitinib Malate (15 mg/kg, oral gavage once daily for 10 days). Mice were euthanized, and choroidal flat mounts were prepared and stained with isolectin B4. CNV area was measured using confocal microscopy [1]

Absorption, Distribution, and Excretion
Absorption
Peak plasma concentrations (Cmax) are typically reached between 6 and 12 hours (Tmax) after oral administration of sunitinib. Food has no effect on the bioavailability of sunitinib. Sunitinib can be taken with or without food. The pharmacokinetic profile of sunitinib was similar in healthy volunteers and in the tested solid tumor patient populations (including patients with gastrointestinal stromal tumors and renal cell carcinoma).
Excretion
Sunitinib is primarily metabolized by the cytochrome P450 enzyme CYP3A4 to produce its major active metabolite, which is further metabolized by CYP3A4. Sunitinib is primarily excreted in feces. In the [14C]sunitinib human weight balance study, 61% of the dose was excreted in feces, and 16% of the administered dose was excreted by the kidneys. Volume of distribution
2230 L (apparent volume of distribution, Vd/F)
Clearance
34 - 62 L/h [Total oral clearance]
Peak plasma concentrations of sunitinib typically occur within 6-12 hours after oral administration. Food has no effect on the bioavailability of sunitinib.
Steady-state concentrations of sunitinib and its major active metabolite are reached within 10 to 14 days. By day 14, the total plasma concentrations of sunitinib and its active metabolite range from 62.9 to 101 ng/mL. No significant changes in the pharmacokinetics of sunitinib or its major active metabolite were observed with repeated daily dosing or repeated dosing cycles in the tested dosing regimens.

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Sunitinib and its main active metabolite are 95% and 90% bound to human plasma proteins, respectively, in vitro.
The apparent volume of distribution (Vd/F) of sunitinib is 2230 L. Within the dose range of 25-100 mg, the area under the plasma concentration-time curve (AUC) and Cmax increase proportionally with the dose.

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Metabolism/Metabolites
Sunitinib is primarily metabolized by the cytochrome P450 enzyme CYP3A4 to produce its main active metabolite, which is subsequently further metabolized by CYP3A4. Sunitinib is primarily metabolized into multiple metabolites by cytochrome P-450 (CYP) isoenzyme 3A4. The major circulating metabolite is an N-deethyl derivative, which has been shown to have the same potency as sunitinib in biochemical and cellular assays; this metabolite accounts for approximately 23-37% of the total plasma concentration of the drug and is also metabolized by CYP3A4. Sunitinib and its major active metabolite are the major drug-related compounds identified in plasma, urine, and feces, accounting for 91.5%, 86.4%, and 73.8% of the radioactivity in mixed samples, respectively. Biological Half-Life: Following a single oral dose in healthy volunteers, the terminal half-lives of sunitinib and its major active metabolite are approximately 40 to 60 hours and 80 to 110 hours, respectively.

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1. In rats: After oral administration of sunitinib malate (20 mg/kg), the oral bioavailability (F) was 48%, the peak plasma concentration (Cmax) was 1.2 μg/mL, the time to peak concentration (Tmax) was 1.5 h, and the terminal half-life (t1/2) was 6.8 h. After intravenous injection (5 mg/kg), the t1/2 was 5.2 h [1]
2. In dogs: After oral administration of sunitinib malate (10 mg/kg), F=36%, Cmax=0.8 μg/mL, Tmax=2 h, t1/2=9.5 h. Plasma protein binding rate >95% (determined by ultrafiltration) [1]
3. In mice: After a single oral administration of sunitinib malate (30 mg/kg), the drug was distributed in a variety of tissues. The highest drug concentrations were found in the liver (12 μg/g) and kidney (8 μg/g) 2 hours after administration; the brain tissue concentration was low (<0.5 μg/g), indicating poor blood-brain barrier penetration [4]
4. Metabolism: In human liver microsomes, sunitinib malate is metabolized to N-deethylsunitinib (the major active metabolite), with a metabolic clearance rate of 1.2 mL/min/mg protein [1]

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
There is currently no information on the clinical use of sunitinib during lactation. Because sunitinib and its metabolites bind to plasma proteins at a rate exceeding 90%, its concentration in breast milk may be very low. However, one metabolite of sunitinib has a long half-life of up to 110 hours and may accumulate in the infant. The manufacturer recommends discontinuing breastfeeding during sunitinib treatment and for at least 4 weeks after the last dose.
◉ Effects on Breastfed Infants
No published information found as of the revision date.
◉ Effects on Lactation and Breast Milk
No published information found as of the revision date.

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1. Acute toxicity in mice: A single oral dose of sunitinib malate (up to 200 mg/kg) did not result in death within 7 days, but mice in the 150-200 mg/kg group experienced transient weight loss (5-8% decrease in 48 hours) and decreased kinetic activity, which recovered within 7 days [4]
2. Subchronic toxicity in rats (oral administration over 28 days): - 25 mg/kg group: No significant changes in body weight, organ weight or hematological parameters (white blood cells, platelets, hemoglobin) [6]
- 50 mg/kg group: Mild decrease in body weight (3-5%), mild increase in liver weight (10-12%), and a 15% decrease in platelet count; no histopathological changes were observed in the liver/kidneys. [6]
- 100 mg/kg group: significant weight loss (8-10%), increased serum ALT (2-fold), increased AST (1.8-fold), severe thrombocytopenia (40% decrease); mild liver necrosis was observed in 2 out of 5 rats. [6]
3. In nude mouse xenotransplantation studies (treatment days 21-35), sunitinib malate (20-50 mg/kg) did not cause more than 10% weight loss or significant organ toxicity (as assessed by histopathological evaluation of liver, kidney and spleen). [2][4]

[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.

Sunitinib malate is an orally bioavailable malate, belonging to the indolinone class of tyrosine kinase inhibitors, and possesses potential antitumor activity. Sunitinib blocks the tyrosine kinase activity of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor β (PDGFRβ), and c-kit, thereby inhibiting angiogenesis and cell proliferation. It also inhibits the phosphorylation of Fms-associated tyrosine kinase 3 (FLT3), another receptor tyrosine kinase expressed in some leukemia cells. Sunitinib is an indole and pyrrole derivative that inhibits VEGFR-2 and PDGFRβ receptor tyrosine kinases. It is used as an antitumor drug to treat gastrointestinal stromal tumors and advanced or metastatic renal cell carcinoma. See also: Sunitinib (containing the active ingredient).

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Drug Indications
Gastrointestinal Stromal Tumors (GIST): Sunitinib is indicated for the treatment of unresectable and/or metastatic gastrointestinal stromal tumors (GIST) in adults who have failed imatinib mesylate therapy due to resistance or intolerance. Metastatic Renal Cell Carcinoma (MRCC): Sunitinib is indicated for the treatment of advanced/metastatic renal cell carcinoma (MRCC) in adults. Pancreatic Neuroendocrine Tumors (pNET): Sunitinib is indicated for the treatment of unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumors that have progressed in adults. Experience with sunitinib as a first-line treatment is limited (see Section 5.1).

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1. Sunitinib malate exerts its antitumor effect through two mechanisms: by blocking the VEGFR/PDGFR signaling pathway to inhibit angiogenesis and by directly inhibiting the proliferation of tumor cells expressing c-Kit/FLT3[1][3]
2. The main active metabolite (N-desethylsunitinib) has similar kinase inhibitory activity to the parent drug (IC50 of VEGFR2: 5-12 nM) and contributes about 30% of the total in vivo activity[1]
3. In preclinical models, sunitinib malate showed synergistic antitumor activity when used in combination with docetaxel (lung cancer) and gemcitabine (pancreatic cancer); the combination therapy resulted in an additional 20-30% reduction in tumor volume compared to monotherapy[7]
4. Sunitinib malate is effective against tumor models resistant to other antiangiogenic drugs (e.g., A549 xenografts resistant to bevacizumab), with a tumor growth inhibition rate (TGI). The TGI of bevacizumab is approximately 60%, while that of PDGFR is approximately 25% [2]. 5. The drug has higher selectivity for tumor-associated kinases (VEGFR, PDGFR) than for housekeeping kinases (e.g., EGFR, Src), thereby reducing off-target toxicity and giving it good preclinical safety [1].

C26H33FN4O7

532.56

532.233

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

341031-54-7

Sunitinib;557795-19-4; Sunitinib Malate;341031-54-7;Sunitinib-d10;1126721-82-1;Sunitinib-d4;1126721-79-6; 342641-94-5; 1275588-72-1 (mesylate) ; 1126641-10-8; 1327155-72-5 (HCl); 1221149-36-5 (acetate); 1332306-95-2 (oxalate)

6456015

Yellow solid powder

1.3600 g/mL at 25 °C(lit.)

156 °C(lit.)

189-191°C

163 °F

n20/D 1.455(lit.)

2.77

6

9

10

38

765

1

FC1C([H])=C([H])C2=C(C=1[H])/C(/C(N2[H])=O)=C(\[H])/C1=C(C([H])([H])[H])C(C(N([H])C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])[H])=O)=C(C([H])([H])[H])N1[H].O([H])[C@]([H])(C(=O)O[H])C([H])([H])C(=O)O[H]

LBWFXVZLPYTWQI-IPOVEDGCSA-N

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-;/t;2-/m.0/s1

N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide;(2S)-2-hydroxybutanedioic acid

sunitinib; SU-11248; SU 11248; Sutent; SU011248 L-malate salt; PHA-290940AD; sunitinib L-malate; Sunitinib malate [USAN]; SU010398; SU11248; SU011248; trade name: Sutent

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.69 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (4.69 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (4.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 4% DMSO+30% PEG 300+ddH2O: 2mg/mL

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Solubility in Formulation 5: 10 mg/mL (18.78 mM) in 100 mM citrate buffer (add these co-solvents sequentially from left to right, and one by one), suspension solution; Need ultrasonic and adjust pH to 5 with HCl.

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 (Please use freshly prepared in vivo formulations for optimal results.)