| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
VEGFR3 (IC50 = 1 nM); VEGFR1 (IC50 = 2 nM); CSF1R (IC50 = 4 nM); FGFR1 (IC50 = 15 nM); VEGFR2 (IC50 = 24 nM)
Sulfatinib targets VEGFR1, VEGFR2, VEGFR3, FGFR1, and CSF1R with high potency and selectivity. It inhibits these receptor tyrosine kinases with IC50s ranging from 1 to 24 nM. By binding to and inhibiting VEGFRs and FGFR1, sulfatinib blocks the signal transduction pathways mediated by these receptors, which are critical for angiogenesis, tumor growth, and metastasis. Sulfatinib strongly blocks VEGF-induced VEGFR2 phosphorylation in HEK293KDR cells and CSF1-stimulated CSF1R phosphorylation in RAW264.7 cells with IC50 of 2 and 79 nM, respectively. |
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| ln Vitro |
SuLfatinib effectively suppresses VEGF-induced VEGFR2 phosphorylation in HEK293KDR cells and CSF1-stimulated CSF1R phosphorylation in RAW264.7 cells, with IC50s of 2 and 24, respectively. It also inhibits mutations in FGFR1, CSF1R, and VEGFR1, 2, and 3. 79 nanometers. Moreover, SuLfatinib has an IC50<50 nM to suppress HUVEC cell growth that is induced by VEGF or FGF[1]. Furthermore, in CHO cells, it has an IC50 of 6.8 μM, making it a hERG brother [2].
Sulfatinib is a potent inhibitor of VEGFR1/2/3, FGFR1, and CSF1R kinases. It demonstrates potent and highly selective tyrosine kinase inhibitory activity with IC50s in a range of 1 to 24 nM. Sulfatinib strongly blocks VEGF-induced VEGFR2 phosphorylation in HEK293KDR cells and CSF1-stimulated CSF1R phosphorylation in RAW264.7 cells with IC50 of 2 and 79 nM, respectively. Its anti-angiogenic and anti-tumor activities are attributed to its ability to inhibit VEGFR- and FGFR1-mediated signal transduction pathways. |
| ln Vivo |
In animal experiments, VEGF-stimulated VEGFR2 phosphorylation in nude mouse lung tissue was regulated by single-pass SuLfatinib. Furthermore, the suppression of FGFR receptor signaling is indicated by the rise in FGF23 levels in 24 channels after 24 hours. shown robust suppression of angiogenesis via VEGFR and FGFR signaling, as seen by the severe growth inhibition shown in several human xenograft models and the significant reduction of CD31 tumor expression. Sulfatinib demonstrated a moderate reduction in tumor development following a single medication treatment in the syngeneic tumor tumor model CT-26 [1]. The AUC and Cmax in mice were 397 ng/mL and 138 ng/mL, respectively, with a sidewall thickness of 10 mg/kg [1].
Sulfatinib is an orally bioavailable inhibitor that has been evaluated in preclinical models for its anti-tumor and anti-angiogenic activities. Upon oral administration, it binds to and inhibits VEGFRs and FGFR1, thereby inhibiting VEGFR- and FGFR1-mediated signal transduction pathways. This leads to the inhibition of angiogenesis and tumor cell proliferation in VEGFR/FGFR1-overexpressing tumor cells. Sulfatinib has been studied for its potential in treating various cancers, including neuroendocrine tumors and solid tumors. |
| Enzyme Assay |
The Z-lyte assay kit is utilized to assess the inhibition activity of KDR kinase. Sulfatinib, the test compound, is present in a 384-well plate with varying concentrations, along with 300 ng/mL of recombinant human KDR catalytic domain, 10 μM of ATP, and 1 μM of substrate peptide in the testing system. The total volume is 10 μL. After one hour at room temperature (25°C) on the shaker, the enzyme inhibition process continues. To halt the reaction, 5 μL of stop solution is added[2].
In vitro enzyme/receptor binding assays for sulfatinib typically involve evaluating its inhibitory activity against purified receptor tyrosine kinases, including VEGFR1, VEGFR2, VEGFR3, FGFR1, and CSF1R. The kinase inhibition activity is tested using the Z-lyte assay kit or similar kinase activity assays. In these assays, the kinase is incubated with a substrate and varying concentrations of sulfatinib, and the phosphorylation of the substrate is measured. The IC50 is determined as the concentration required to inhibit kinase activity by 50%. |
| Cell Assay |
For in vitro cell-based assays, sulfatinib is dissolved in DMSO (92 mg/mL; 191.43 mM) and applied to cultured cells such as HEK293KDR cells or RAW264.7 cells at concentrations ranging from 1 nM to 10 µM. The effects on VEGFR2 phosphorylation (in HEK293KDR cells) or CSF1R phosphorylation (in RAW264.7 cells) are assessed by Western blotting or ELISA after treatment with sulfatinib. The anti-proliferative and anti-angiogenic activities are evaluated by measuring cell proliferation, migration, and tube formation assays.
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| Animal Protocol |
Male ICR mice (n = 6 per group; weight 20–30 g) are used to study the phamacokinetics of sulfatinib following a single intravenous and oral dose of 2.5 and 10 mg/kg, respectively. Sulfatinib is dissolved in DMSO (0.25%)-solutol (10%)-ethanol (10%)-physiological saline (797.75%) at a concentration of 0.25 mg/mL for intravenous dosing formulation. Additionally, 0.5% CMC-Na is used to prepare the p.o. Dosing formulation (1 mg/mL). Following intravenous or PO dosage, blood is drawn via the ophthalmic vein at 0 (pre-close), 5, 15, 30 minutes, and 1, 1.5, 2, 4, 8, and 24 hours. The blood is then anticoagulated using heparin-Na. Following centrifugation, plasma samples are separated, and protein is precipitated using an internal standard containing acetonitrilel[2].
In vivo animal studies for sulfatinib are typically conducted in mouse xenograft models of cancer. The compound is administered orally at doses ranging from 1-100 mg/kg. Anti-tumor efficacy is evaluated by measuring tumor volume, tumor weight, and angiogenesis. The inhibition of VEGFR and FGFR1 signaling in tumor tissues is confirmed by Western blotting or immunohistochemistry to assess the phosphorylation status of these receptors and downstream signaling molecules. |
| ADME/Pharmacokinetics |
Sulfatinib has a molecular weight of 480.58 g/mol and a molecular formula of C24H28N6O3S. It is soluble in DMSO (92 mg/mL; 191.43 mM) but poorly soluble in water and ethanol (<1 mg/mL). The compound is typically stored as a powder at -20°C for long-term stability (up to 3 years). Sulfatinib is also known as HMPL-012 or surufatinib. It has the SMILES O=S(CC1=CC=CC(NC2=NC=CC(OC3=CC4=C(NC(C)=C4)C=C3)=N2)=C1)(NCCN(C)C)=O.
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| Toxicity/Toxicokinetics |
Sulfatinib has a manageable toxicity profile, consistent with other tyrosine kinase inhibitors. Common side effects include hypertension, fatigue, diarrhea, and proteinuria. Hepatotoxicity, including elevated liver enzymes, has been reported. Hematological toxicities, such as thrombocytopenia and neutropenia, can occur. Gastrointestinal disturbances, including nausea and vomiting, are also reported. The risk of bleeding and thrombosis is associated with VEGFR inhibition. Regular monitoring of blood pressure, liver function, and complete blood counts is recommended during therapy.
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| References | |
| Additional Infomation |
Surufatinib is being investigated in the clinical trial NCT02588170 (a phase III study of sulfatinib for advanced extrapancreatic neuroendocrine tumors). Surufatinib is a small molecule inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3, and fibroblast growth factor receptor type 1 (FGFR1) with high oral bioavailability and potential antitumor and antiangiogenic activities. After oral administration, sulfatinib binds to and inhibits VEGFR and FGFR1, thereby inhibiting VEGFR and FGFR1-mediated signal transduction pathways. This leads to reduced angiogenesis and tumor cell proliferation in VEGFR/FGFR1-overexpressing tumor cells. VEGFR and FGFR1 expression may be upregulated in various tumor cell types.
Indications For the treatment of all malignancies (excluding central nervous system tumors, hematopoietic and lymphoid tissue tumors), as well as hematopoietic and lymphoid tissue malignancies. Sulfatinib (HMPL-012), also known as surufatinib, is an orally bioavailable, small molecule inhibitor of VEGFR1/2/3, FGFR1, and CSF1R with potential antineoplastic and anti-angiogenic activities. It is a potent and highly selective tyrosine kinase inhibitor with IC50s in a range of 1 to 24 nM. Upon oral administration, sulfatinib binds to and inhibits VEGFRs and FGFR1, thereby inhibiting VEGFR- and FGFR1-mediated signal transduction pathways. This leads to the inhibition of angiogenesis and tumor cell proliferation. Sulfatinib has been studied for its potential in treating various cancers, including neuroendocrine tumors and solid tumors. |
| Molecular Formula |
C24H28N6O3S
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|---|---|
| Molecular Weight |
480.587
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| Exact Mass |
480.194
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| Elemental Analysis |
C, 59.98; H, 5.87; N, 17.49; O, 9.99; S, 6.67
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| CAS # |
1308672-74-3
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| Related CAS # |
1308672-74-3;1816307-67-1
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| PubChem CID |
52920501
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
712.9±70.0 °C at 760 mmHg
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| Flash Point |
385.0±35.7 °C
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| Vapour Pressure |
0.0±2.3 mmHg at 25°C
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| Index of Refraction |
1.658
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| LogP |
3.06
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
34
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| Complexity |
733
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C([H])([H])C1C([H])=C([H])C([H])=C(C=1[H])N([H])C1=NC([H])=C([H])C(=N1)OC1C([H])=C([H])C2=C(C=1[H])C([H])=C(C([H])([H])[H])N2[H])(N([H])C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])[H])(=O)=O
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| InChi Key |
TTZSNFLLYPYKIL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H28N6O3S/c1-17-13-19-15-21(7-8-22(19)27-17)33-23-9-10-25-24(29-23)28-20-6-4-5-18(14-20)16-34(31,32)26-11-12-30(2)3/h4-10,13-15,26-27H,11-12,16H2,1-3H3,(H,25,28,29)
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| Chemical Name |
N-[2-(dimethylamino)ethyl]-1-[3-[[4-[(2-methyl-1H-indol-5-yl)oxy]pyrimidin-2-yl]amino]phenyl]methanesulfonamide
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| Synonyms |
HMPL012; HMPL012; HMPL 012; surufatinib; Sulfatinib
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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 |
| 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) |
DMSO: ~96 mg/mL (~199.8 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.33 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.33 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 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.33 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0808 mL | 10.4039 mL | 20.8078 mL | |
| 5 mM | 0.4162 mL | 2.0808 mL | 4.1616 mL | |
| 10 mM | 0.2081 mL | 1.0404 mL | 2.0808 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05077384 | Recruiting | Drug: Surufatinib | Neuroendocrine Tumors Non-hematologic Malignancy |
Hutchison Medipharma Limited | September 2, 2021 | Phase 1 Phase 2 |
| NCT04579679 | Active Recruiting |
Drug: Surufatinib | Neuroendocrine Tumours Small Intestinal NET |
Hutchmed | August 13, 2021 | Phase 2 |
| NCT05171439 | Recruiting | Drug: Surufatinib | Hepatocellular Carcinoma | he Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School |
March 1, 2022 | Phase 2 |
| NCT05590572 | Not yet recruiting | Drug: Sulfatinib Drug: Etoposide |
Osteosarcoma | Second Affiliated Hospital, School of Medicine, Zhejiang University |
January 2023 | Phase 1 Phase 2 |
| NCT02549937 | Active Recruiting |
Drug: surufatinib | Tumors | Hutchison Medipharma Limited | November 2015 | Phase 1 Phase 2 |
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