Sunitinib malate
Sunitinib malate, also called sunitinib, is a novel, oral, multi-targeted , small molecule oxindole tyrosine kinase inhibitor which inhibits multiple receptor tyrosine kinases including platelet-derived growth factor receptor ( and (, vascular endothelial growth factor receptor 1, 2 and 3, c-KIT, FLT3 kinase, colony-stimulating factor 1 receptor and RET kinase [2][3] [4]. The IC50 of sunitinib is approximately 10-20 ng/ml to NB cell lines, which is within the clinically relevant human trough serum concentration (50-100 ng/ml) [1].
Receptor tyrosine kinases activated a number of different intracellular signaling pathways [5].
In neuroblastoma (NB) cell lines, SKN-BE (2), NUB-7, SH-SY5Y and LAN-5, sunitinib significantly inhibited cell proliferation after a treatment for 48 hours, in a concentration-dependent manner [1].
Treatment with 20, 30 or 40 mg/kg of sunitinib made NOD/SCID mice inoculated with xenograft tumor cells show significant reduction (P
References:
[1]. Libo Zhang, Kristen M. Smith, Amy Lee Chong, et al. In Vivo Antitumor and Antimetastatic Activity of Sunitinib in Preclinical Neuroblastoma Mouse Model. Neoplasia, 2009, 11: 426-435.
[2]. Hassane Izzedine, Irina Buhaescu, Olivier Rixe, et al. Sunitinib malate. Cancer Chemother Pharmacol, 2007, 60: 357-364.
[3]. M. L. Telli, R. M. Witteles, G. A. Fisher, et al. Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate. Annals of Oncology, 2008, 19: 1613–1618.
[4]. Edwin P. Rock, Vicki Goodman, Janet X. Jiang, et al. Food and Drug Administration Drug Approval Summary: Sunitinib Malate for the Treatment of Gastrointestinal Stromal Tumor and Advanced Renal Cell Carcinoma. The Oncologist, 2007, 12: 107-113.
[5]. C. J. Marshall. Specificity of Receptor Tyrosine Kinase Signaling: Transient versus Sustained Extracellular Signal-Regulated Kinase Activation. Cel, 1995, 80: 179-185.
- 1. Zikang Xing, Xuewen Li, et al. "IDO1 Inhibitor RY103 Suppresses Trp-GCN2-Mediated Angiogenesis and Counters Immunosuppression in Glioblastoma." Pharmaceutics. 2024 Jun 28;16(7):870. PMID: 39065567
- 2. Huijiao Jiang, Xiaoyi Wang, et al. "Effect of Sunitinib against Echinococcus multilocularis through inhibition of VEGFA-induced angiogenesis." Research Square. February 1st, 2023.
- 3. Wu F, Wu D, et al. "Generation of hepato-biliary organoids from human induced pluripotent stem cells." J Hepatol. 2019 Jan 7. pii: S0168-8278(19)30002-9. PMID:30630011
- 4. Lin M, Chen B. "Advances in the drug therapies of acute myeloid leukemia (except acute wpromyelocytic leukemia)." Drug Des Devel Ther. 2018 Apr 30;12:1009-1017. PMID:29750014
| Physical Appearance | A solid |
| Storage | Store at 4°C |
| M.Wt | 532.56 |
| Cas No. | 341031-54-7 |
| Formula | C22H27FN4O2·C4H6O5 |
| Synonyms | SU 11248,SU11248,SU-11248,Sunitinib |
| Solubility | ≥26.65 mg/mL in DMSO; insoluble in EtOH; ≥4.6 mg/mL in H2O with ultrasonic |
| Chemical Name | 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 |
| SDF | Download SDF |
| Canonical SMILES | CCN(CC)CCNC(=O)C1=C(NC(=C1C)C=C2C3=C(C=CC(=C3)F)NC2=O)C.C(C(C(=O)O)O)C(=O)O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
|
Cell lines |
NIH-3T3 cells, HUVECs |
|
Preparation method |
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Applications |
In serum-starved NIH-3T3 cells expressing VEGFR2 or PDGFRβ, Sunitinib inhibited VEGF-dependent VEGFR2 phosphorylation and PDGF-dependent PDGFRβ phosphorylation. Sunitinib inhibited VEGF-induced proliferation of serum-starved HUVECs with IC50 of 40 nM, and inhibited PDGF-induced proliferation of NIH-3T3 cells overexpressing PDGFRβ or PDGFRα with IC50 of 39 nM and 69 nM, respectively. |
| Animal experiment [1]: | |
|
Animal models |
Tumor xenograft mouse models bearing HT-29, A431, Colo205, H-460, SF763T, C6, A375, or MDA-MB-435 cells |
|
Dosage form |
Oral dosing, 20-80 mg/kg/day, once daily |
|
Application |
Sunitinib (20-80 mg/kg/day) exhibited 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. Sunitinib (80 mg/kg/day for 21 days) led to complete tumor regression in six of eight mice, without tumor re-growing during a 110-day observation period after the end of treatment. Sunitinib treatment significantly decreased tumor MVD, with ~40% reduction in SF763T glioma tumors. SU11248 completely inhibited additional tumor growth of luciferase-expressing PC-3M xenografts, despite no reduction in tumor size. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1]. Mendel D B, Laird A D, Xin X, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors[J]. Clinical Cancer Research, 2003, 9(1): 327-337. |
|
| Description | Sunitinib Malate is a multi-targeted inhibitor of RTK for VEGFR2 (Flk-1) and PDGFRβ with IC50 of 80 nM and 2 nM. | |||||
| Targets | VEGFR2 (Flk-1) | PDGFRβ | ||||
| IC50 | 80 nM | 2 nM | ||||
Quality Control & MSDS
- View current batch:
Chemical structure
Related Biological Data
Related Biological Data
Related Biological Data
