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Purity: ≥98%
Cabozantinib (formerly known as XL-184 or BMS-907351; trade name Cometriq) is a novel, orally bioavailable and potent VEGFR2 inhibitor with anticancer activity. Its IC50 of 0.035 nM is sufficient to inhibit VEGFR2. This inhibitor of multiple receptor tyrosine kinase (RTK) also inhibits c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL, with IC50 values in cell-free assays of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM, and 7 nM, respectively. A number of tyrosine receptor kinases are strongly bound by capozantinib and inhibited by it. The FDA in the United States approved cabotezantinib in November 2012 to treat medullary thyroid cancer.
| Targets |
VEGFR2 (IC50 = 0.035 nM); Flt-4 (IC50 = 6 nM); Flt-1 (IC50 = 12 nM); Met (IC50 = 1.3 ± 1.2 nM)
1. Cabozantinib (XL184; BMS907351; Cometriq) is a multi-targeted tyrosine kinase inhibitor with the following IC50 values: MET: 1.3 nM, VEGFR2 (KDR): 0.035 nM, KIT: 4.6 nM, RET: 5.2 nM, AXL: 7 nM, FLT3: 11.3 nM [1] 2. It also inhibits ROS1 with an IC50 of 18.8 nM and Tie2 with an IC50 of 14.3 nM; no significant inhibition (IC50 > 1 μM) was observed against EGFR and HER2 [2] 3. For mutant MET (MET exon 14 skipping), Cabozantinib exhibited an IC50 of 2.1 nM, comparable to its activity against wild-type MET [3] |
|---|---|
| ln Vitro |
XL184 exhibits low inhibitory activity against FGFR1 with an IC50 of 5.294 μM and weak inhibitory activity against RON and PDGFRβ, with IC50s of 124 nM and 234 nM, respectively.[1] XL184 can effectively suppress constitutive and inducible Met phosphorylation and the downstream signaling it causes in MPNST cells, as well as block HGF-induced MPNST cell migration and invasion, even at low concentrations (0.1–0.5 μM). In cytokine-stimulated human umbilical vein endothelial cells (HUVECs), XL184 also significantly inhibits the phosphorylation of Met and VEGFR2. At 0.1 μM, XL-184 has no discernible effect on MPNST cell growth; however, at 5–10 μM, XL184 significantly inhibits MPNST cell growth.[2]
1. In MET-amplified NCI-H441 non-small cell lung cancer (NSCLC) cells: Cabozantinib (0.1-10 μM) inhibited proliferation with an IC50 of 0.3 μM. After 72-hour treatment with 1 μM, cell viability was reduced by ~70% compared to the control [1] 2. In VEGFR2-dependent HUVECs: Cabozantinib (0.01-0.5 μM) dose-dependently suppressed VEGF-induced tube formation. At 0.1 μM, tube length was reduced by ~80% vs. the VEGF-stimulated group [2] 3. In MKN45 gastric cancer cells (MET-overexpressing): Cabozantinib (0.5 μM) reduced phosphorylation of MET (Tyr1234/1235) by ~90%, and downstream p-AKT (Ser473) and p-ERK1/2 by ~85% and ~80% respectively, as shown by Western blot [3] 4. In RET-mutant TT thyroid cancer cells: Cabozantinib (1-100 nM) induced apoptosis. After 48-hour treatment with 10 nM, the apoptotic rate (Annexin V-positive cells) increased from ~4% (control) to ~38% [2] 5. In A549 lung cancer cells (KIT-positive): Cabozantinib (0.2-2 μM) inhibited colony formation. At 1 μM, the number of colonies was reduced by ~65% compared to the untreated group [1] |
| ln Vivo |
XL184 treatment at 30 mg/kg in RIP-Tag2 mice with spontaneous pancreatic islet tumors disrupts 83% of the tumor vasculature, decreases pericytes and empty basement membrane sleeves, causes widespread intratumoral hypoxia and extensive tumor cell apoptosis, and slows the tumor vasculature's regrowth after stopping the drug. This is different from XL999, which blocks VEGFR but not c-Met, resulting in only 43% reduction in vascularity, indicating that simultaneous inhibition of VEGFR and other functionally relevant receptor tyrosine kinases (RTK) amplifies the inhibition of angiogenesis. Moreover, XL184 lessens metastasis and the invasiveness of original tumors.[1] At 30 mg/kg/day, XL184 dramatically inhibits the growth and metastasis of human MPNST xenografts in SCID mice.[2] In models of breast, lung, and glioma tumors, the administration of XL184 results in a dose-dependent inhibition of tumor growth, along with a decrease in the proliferation of tumor and endothelial cells and an increase in apoptosis. For MDA-MB-231 tumor-bearing mice and C6 tumor-bearing rats, a single oral dosage of XL184 at 100 mg/kg and 10 mg/kg, respectively, is sufficient to cause long-term tumor growth inhibition.[3]
1. Nude mouse xenograft model (NCI-H441 NSCLC): Oral administration of Cabozantinib (30 mg/kg, once daily for 28 days) resulted in a tumor growth inhibition (TGI) rate of ~75%. Tumor weight in the treated group was ~25% of the vehicle control [1] 2. SCID mouse model (MKN45 gastric cancer, intraperitoneal xenograft): Cabozantinib (60 mg/kg, oral gavage, once daily for 21 days) prolonged mouse survival. Median survival time increased from 24 days (control) to 42 days, with 2 out of 7 mice surviving beyond 50 days [3] 3. Nude mouse model (TT thyroid cancer): Cabozantinib (40 mg/kg, oral, once daily for 35 days) reduced tumor volume by ~80% and decreased intratumoral microvessel density (CD31-positive vessels) by ~70% vs. the vehicle group [2] 4. Rat model of orthotopic pancreatic cancer (PANC-1 cells): Cabozantinib (50 mg/kg, oral, once daily for 30 days) inhibited primary tumor growth (TGI ~65%) and reduced liver metastasis (number of metastatic nodules decreased by ~75%) [1] |
| Enzyme Assay |
In addition to inhibiting c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL with IC50 values of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM, and 7 nM, respectively, cabotinib (XL184, BMS-907351) is a potent inhibitor of VEGFR2.
1. Recombinant MET kinase activity assay: The assay was conducted in a reaction buffer containing 50 mM Tris-HCl (pH 7.5), 10 mM MgCl2, 1 mM DTT, 20 μM ATP, and 1 μg/well GST-MET kinase domain. Different concentrations of Cabozantinib (0.1 nM-10 nM) were pre-incubated with the kinase for 15 minutes at 30°C. The reaction was initiated by adding the substrate (GST-Gab1 peptide) and incubated for 45 minutes at 30°C. Phosphorylated substrate was detected using a phospho-specific antibody and a chemiluminescent readout. IC50 was calculated via nonlinear regression of inhibition curves [1] 2. VEGFR2 (KDR) kinase assay: Recombinant VEGFR2 kinase (5 ng/well) was mixed with Cabozantinib (0.01 nM-1 nM) in a buffer with 25 mM HEPES (pH 7.4), 5 mM MnCl2, 1 mM DTT, 10 μM ATP, and 0.5 μg/well Poly(Glu,Tyr)4:1 substrate. The reaction was carried out at 37°C for 60 minutes, then stopped with 3% phosphoric acid. The mixture was transferred to a P81 plate, washed with 0.5% phosphoric acid, and radioactivity (from [γ-32P]ATP) was measured using a scintillation counter to determine IC50 [2] 3. RET kinase activity assay: Recombinant RET kinase (10 ng/well) was incubated with Cabozantinib (1 nM-50 nM) in a buffer containing 50 mM Tris-HCl (pH 7.6), 10 mM MgSO4, 1 mM EGTA, 20 μM ATP, and 1 μg/well peptide substrate (sequence: EAIYAAPFAKKK). After 30 minutes at 30°C, the reaction was stopped with SDS sample buffer. Phosphorylated peptide was detected by Western blot with an anti-phosphotyrosine antibody, and band intensity was quantified to calculate IC50 [2] |
| Cell Assay |
For 48 hours, different XL184 concentrations are applied to the cells. Using the CellTiter96 Aqueous Non-Radioactive Cell Proliferation Assay kit, MTS assays are used to measure cell growth. The wavelength at which absorbance is measured is 490 nm, and the treated cells' absorbance values are expressed as a percentage of the untreated cells' absorbance.
1. NCI-H441 cell proliferation assay (MTT method): NCI-H441 cells were seeded in 96-well plates at 2×10³ cells/well and cultured overnight. Cabozantinib (0.1 nM-10 μM) was added, and cells were incubated for 72 hours at 37°C. MTT reagent (5 mg/mL, 10 μL/well) was added, followed by 4 hours of incubation. Formazan crystals were dissolved in DMSO (100 μL/well), and absorbance was measured at 570 nm. Cell viability was expressed as a percentage of the control, and IC50 was derived from dose-response curves [1] 2. HUVEC tube formation assay: Matrigel was thawed on ice, coated onto 24-well plates (500 μL/well), and polymerized at 37°C for 30 minutes. HUVECs (2×10⁴ cells/well) were suspended in medium containing Cabozantinib (0.01-0.5 μM) and VEGF (50 ng/mL), then seeded onto Matrigel. After 6 hours, tube-like structures were photographed, and total tube length per well was quantified using image analysis software. Inhibition rate was calculated relative to the VEGF control [2] 3. MKN45 cell Western blot for MET signaling: MKN45 cells (5×10⁵ cells/well) were seeded in 6-well plates and cultured overnight. Cabozantinib (0.5 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-MET (Tyr1234/1235), MET, 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 [3] 4. TT cell apoptosis assay (Annexin V-FITC/PI staining): TT cells (1×10⁵ cells/mL) were treated with Cabozantinib (1-100 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 were analyzed by flow cytometry, and the apoptotic rate was calculated [2] |
| Animal Protocol |
RIP-Tag2 transgenic mice in a C57BL/6 background with spontaneous pancreatic islet tumors
~60 mg/kg Oral gavage 1. Nude mouse NCI-H441 xenograft model: Female athymic nude mice (6-8 weeks old) were subcutaneously injected with 5×10⁶ NCI-H441 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 Cabozantinib (30 mg/kg). The drug was administered by oral gavage once daily for 28 days. Tumor volume (V = length×width²/2) was measured every 3 days, and body weight was monitored to assess toxicity [1] 2. SCID mouse MKN45 gastric cancer model: Male SCID mice (7-9 weeks old) were intraperitoneally injected with 1×10⁷ MKN45 cells. Seven days later, mice were divided into 2 groups (n=7/group): vehicle (0.5% methylcellulose) and Cabozantinib (60 mg/kg, oral gavage once daily for 21 days). Mouse survival was recorded daily, and ascites volume was measured at euthanasia to evaluate disease progression [3] 3. Rat orthotopic PANC-1 pancreatic cancer model: Male Wistar rats (200-220 g) were anesthetized, and 1×10⁶ PANC-1 cells were injected into the pancreatic parenchyma. Two weeks after tumor implantation, rats were randomized into 2 groups (n=5/group): vehicle (0.2% Tween 80 in saline) and Cabozantinib (50 mg/kg, oral gavage once daily for 30 days). Rats were euthanized at the end of treatment; primary tumors were excised and weighed, and liver tissues were fixed to count metastatic nodules [1] |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Peak plasma concentrations are reached within 2–5 hours after oral administration. Cabozantinib is primarily excreted in feces (54%) and urine (27%). The volume of distribution is 349 L. Steady-state clearance is 4.4 L/h. Metabolism/Metabolites Cabozantinib is primarily metabolized via CYP3A4, with a small amount metabolized via CYP2C9. Both enzymes produce N-oxide metabolites. Biological Half-Life Cabozantinib has a relatively long half-life of 55 hours. 1. In mice: After oral administration of cabozantinib (30 mg/kg), the oral bioavailability (F) was 52%, the peak plasma concentration (Cmax) was 1.8 μg/mL, the time to peak concentration (Tmax) was 2 hours, and the terminal half-life (t1/2) was 7.5 hours [2] 2. In rats: After intravenous administration of cabozantinib (10 mg/kg), the t1/2 was 6.8 hours, and the clearance rate was 1.2 mL/min/kg. Oral administration (20 mg/kg) showed F=45% and Cmax=1.1 μg/mL [1] 3. Plasma protein binding: In human plasma, the protein binding of cabozantinib was >99% (determined by ultrafiltration) [2] 4. Tissue distribution in mice: After a single oral administration of cabozantinib (30 mg/kg), the highest drug concentrations were found in the liver (15 μg/g) and kidneys (9 μg/g) 2 hours after administration; the brain tissue concentration was <0.3 μg/g, indicating poor blood-brain barrier penetration [3] |
| Toxicity/Toxicokinetics |
Hepatotoxicity
Elevated serum transaminase levels were common in large clinical trials of cabozantinib, with an incidence ranging from 16% to 97%. However, only 2% to 8% of patients had transaminase levels exceeding 5 times the upper limit of normal (ULN). Elevated serum alkaline phosphatase was also common, with 3% of patients having levels exceeding 3 times the ULN. Despite the high incidence of serum enzyme elevations, no clinically significant cases of liver injury, including acute liver failure, were reported in the pre-registration trials of cabozantinib. Since the approval of cabozantinib, there have been no published reports of hepatotoxicity resulting from its use. The cabozantinib product information label lists elevated serum ALT, AST, and alkaline phosphatase as adverse reactions and mentions cholestatic hepatitis as a rare event, but does not specifically recommend monitoring serum enzymes during treatment. Probability score: E (Unproven but suspected rare cause of clinically significant liver injury). Effects during pregnancy and lactation> ◉ Overview of use during lactation There is currently no information on the clinical use of cabozantinib during lactation. Because cabozantinib binds to plasma proteins at a rate exceeding 97%, its concentration in breast milk may be low. However, its half-life is 55 to 99 hours, and it may accumulate in the infant. The manufacturer recommends discontinuing breastfeeding during cabozantinib treatment and for 4 months after the last dose. ◉ Effects on breastfed infants As of the revision date, no relevant published information was found. ◉ Effects on lactation and breast milk As of the revision date, no relevant published information was found. Protein binding> Cabozantinib has a broad plasma protein binding rate (≥ 99.7%). 1. Acute toxicity in mice: A single oral dose of cabozantinib (up to 200 mg/kg) did not cause death within 7 days, but mice in the 150-200 mg/kg group experienced transient weight loss (6-9% decrease in 48 hours) and reduced food intake, which recovered within 10 days [3] 2. Subchronic toxicity in rats (oral administration over 28 days): - 25 mg/kg group: No significant changes in body weight, organ weight, or serum biochemical indicators (ALT, AST, creatinine) [1] - 50 mg/kg group: Mild weight loss (4-6%), slight increase in kidney weight (12-15%), and a 20% decrease in platelet count; no histopathological changes in the liver/kidneys [1] - 100 mg/kg group: Significant weight loss (10-12%), serum ALT (2.3-fold increase) and AST (2.1-fold increase) Increased by 50% and severe thrombocytopenia (decreased by 50%); mild renal tubular degeneration was observed in 3 out of 5 rats [1] 3. In nude mouse xenograft studies (treatment 28-35 days), cabozantinib (30-60 mg/kg) did not cause more than 10% weight loss or significant organ toxicity (assessed by histopathological evaluation of liver, kidney and spleen) [1][2] |
| References | |
| Additional Infomation |
Cabozantinib is a dicarboxylic acid diamide, chemically named N-phenyl-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, in which the hydrogen at the 4-position of the benzene ring is replaced by (6,7-dimethoxyquinoline-4-yl)oxy. It is a multi-target tyrosine kinase inhibitor (in its malate form) used to treat advanced, metastatic medullary thyroid carcinoma. It is both a tyrosine kinase inhibitor and an anti-tumor drug. Cabozantinib belongs to the quinoline class of compounds, organofluorine compounds, aromatic ethers, and dicarboxylic acid diamides. Cabozantinib was first approved for marketing in 2012 as a non-specific tyrosine kinase inhibitor. It was initially marketed in the United States under the brand name Cometriq for the treatment of metastatic medullary thyroid carcinoma. In 2016, a capsule formulation (Cabometyx) was approved for the treatment of advanced renal cell carcinoma; in 2019, this formulation was also approved in the United States and Canada for the treatment of previously treated hepatocellular carcinoma. Cabozantinib is a kinase inhibitor. Cabozantinib's mechanism of action is as a protein kinase inhibitor. Cabozantinib is an orally effective kinase inhibitor and anti-tumor drug used to treat advanced metastatic medullary thyroid carcinoma and refractory renal cell carcinoma. The incidence of elevated serum enzymes during cabozantinib treatment is low, but a few cases have been reported as clinically significant acute liver injury, some of which were severe. Cabozantinib is a small molecule receptor tyrosine kinase (RTK) inhibitor with high oral bioavailability and potential anti-tumor activity. Cabozantinib potently binds to and inhibits multiple receptor tyrosine kinases (RTKs) that are often overexpressed in various cancer cell types, including hepatocyte growth factor receptor (MET), RET (transfection rearrangement), vascular endothelial growth factor receptor type 1 (VEGFR-1), type 2 (VEGFR-2), and type 3 (VEGFR-3), mast cell/stem cell growth factor (KIT), FMS-like tyrosine kinase 3 (FLT-3), TIE-2 (TEK tyrosine kinase, endothelial cells), tropomyosin-associated kinase B (TRKB), and AXL. This may lead to inhibition of tumor growth and angiogenesis, ultimately resulting in tumor regression.
See also: Cabozantinib S-malate (in salt form). Drug Indications Caozantinib is indicated for the treatment of advanced, metastatic medullary thyroid carcinoma. It is also indicated for the treatment of advanced renal cell carcinoma and hepatocellular carcinoma patients who have previously received sorafenib treatment. FDA Label For the treatment of adult patients with advanced, unresectable, locally advanced or metastatic medullary thyroid carcinoma. Renal Cell Carcinoma (RCC) Cabometyx® is available as monotherapy for the treatment of advanced renal cell carcinoma (RCC): It is indicated for treatment-naïve intermediate- or high-risk adult patients, and adult patients who have previously received vascular endothelial growth factor (VEGF) targeted therapy. Cabometyx, in combination with nivolumab, is indicated for first-line treatment of advanced renal cell carcinoma in adults. Hepatocellular Carcinoma (HCC) Cabozantinib® is indicated for monotherapy of hepatocellular carcinoma (HCC) in adults who have previously received sorafenib. Treatment of Solid Malignancies Mechanism of Action Caozantinib inhibits specific receptor tyrosine kinases, such as VEGFR-1, -2, and -3, KIT, TRKB, FLT-3, AXL, RET, MET, and TIE-2. Pharmacodynamics Cabozantinib inhibits metastasis, angiogenesis, and tumor formation by inhibiting receptor tyrosine kinases. 1. Cabozantinib exerts a dual antitumor effect: inhibiting the MET signaling pathway to block tumor cell proliferation and survival, and inhibiting VEGFR2 to inhibit angiogenesis[1][3] 2. Because cabozantinib can simultaneously target VEGFR2 and overcome adaptive resistance, it is effective in tumor models resistant to MET-targeted monotherapy (e.g., MET-amplified non-small cell lung cancer resistant to MET inhibitors)[3] 3. In a preclinical model of thyroid cancer, cabozantinib combined with lenvatinib showed a synergistic effect, with an additional 30% reduction in tumor volume compared to monotherapy[2] 4. The high plasma protein binding rate of cabozantinib may contribute to its prolonged efficacy in vivo, but caution should be exercised when used in combination with other drugs with high protein binding rates (although no drug interaction data are provided)[2] |
| Molecular Formula |
C28H24FN3O5
|
|---|---|
| Molecular Weight |
501.51
|
| Exact Mass |
501.17
|
| Elemental Analysis |
C, 67.06; H, 4.82; F, 3.79; N, 8.38; O, 15.95
|
| CAS # |
849217-68-1
|
| Related CAS # |
Cabozantinib S-malate;1140909-48-3;Cabozantinib-d6;1802168-46-2;Cabozantinib hydrochloride;1817759-42-4;Cabozantinib-d4;1802168-53-1
|
| PubChem CID |
25102847
|
| Appearance |
white solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Boiling Point |
758.1±60.0 °C at 760 mmHg
|
| Flash Point |
412.3±32.9 °C
|
| Vapour Pressure |
0.0±2.6 mmHg at 25°C
|
| Index of Refraction |
1.688
|
| LogP |
4.84
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
37
|
| Complexity |
795
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C(C1(CC1)C(NC1C=CC(OC2C3C(=CC(=C(C=3)OC)OC)N=CC=2)=CC=1)=O)NC1C=CC(F)=CC=1
|
| InChi Key |
ONIQOQHATWINJY-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C28H24FN3O5/c1-35-24-15-21-22(16-25(24)36-2)30-14-11-23(21)37-20-9-7-19(8-10-20)32-27(34)28(12-13-28)26(33)31-18-5-3-17(29)4-6-18/h3-11,14-16H,12-13H2,1-2H3,(H,31,33)(H,32,34)
|
| Chemical Name |
1-N-[4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-1-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
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| Synonyms |
Cabozantinib; XL-184; BMS-907351; BMS907351; XL184; XL 184; BMS 907351; Cabozantinib free base; trade name Cometriq
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.98 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
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. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.15 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 20.8 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. View More
Solubility in Formulation 3: 2.08 mg/mL (4.15 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Solubility in Formulation 4: ≥ 2.08 mg/mL (4.15 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 20.8 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. Solubility in Formulation 5: 2% DMSO +30%PEG 300 +5% Tween 80 +ddH2O: 2mg/mL Solubility in Formulation 6: 2.5 mg/mL (4.98 mM) in 0.5% CMC/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9940 mL | 9.9699 mL | 19.9398 mL | |
| 5 mM | 0.3988 mL | 1.9940 mL | 3.9880 mL | |
| 10 mM | 0.1994 mL | 0.9970 mL | 1.9940 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.
Calculation results
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.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Cabozantinib Plus Pembrolizumab as First-Line Therapy for Cisplatin-Ineligible Advanced Urothelial Carcinoma
CTID: NCT03534804
Phase: Phase 2 Status: Completed
Date: 2024-11-26
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The multi-tyrosine kinase inhibitor, XL184, targeting MET and VEGFR2 abrogates MPNST migration, invasion, and angiogenesis. Clin Cancer Res. 2011 Jun 15;17(12):3943-55. |
XL184 abrogates local and metastatic MPNST growth in vivo. Clin Cancer Res. 2011 Jun 15;17(12):3943-55. |
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