Vorolanib (Synonyms: CM082; X-82) |
| رقم الكتالوجGC38380 |
فورولانيب Vorolanib (CM082) هو مثبط فعال عن طريق الفم ، ومثبط فعّال متعدد للكيناز VEGFR / PDGFR
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1013920-15-4
Sample solution is provided at 25 µL, 10mM.
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Vorolanib (X-82; CM082) is an orally active dual inhibitor of vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) multikinases with IC50 values of 0.052μM and 0.26μM, respectively[1]. Vorolanib is a novel tyrosine receptor kinase inhibitor with antiangiogenic and antitumor activities[2]. Vorolanib is a potential inhibitor of ATP-binding cassette (ABC) transporters with the potential to reverse multidrug resistance (MDR)[3].
In vitro, treatment of MDR cells (S1-MI-80 and H460/MX20) with vorolanib (0-100μM) for 96 h inhibited [125I]-IAAP photoaffinity labeling, increased ABCG2 ATPase activity, and reduced rhodamine 123 (Rho 123) efflux[3]. Treatment of HUVEC cells with vorolanib (10µM) for 48h significantly inhibited the proliferation, migration, invasion, and tube formation of HUVECs stimulated with rHuVEGF165[4]. Treatment of HUVEC cells with Vorolanib (0.01, 0.1, 1µM) inhibited cell growth with an IC50 of 0.031±0.005µM, inhibited phosphorylation of VEGFR and downstream signaling molecules, and inhibited angiogenesis and cell migration[5].
In vivo, subcutaneous injection of Vorolanib (80, 160mg/kg) in mice inoculated with H3255 cells slowed tumor growth and significantly inhibited phosphorylation of ERK1/2 and AKT[5]. Oral treatment of rats with choroidal neovascularization (CNV) model with Vorolanib (10, 30mg/kg) reduced CNV leakage, caused regression of CNV lesions, and reduced p-VEGFR-2 aggregation in the retinal pigment epithelium and outer plexiform layer[6]. Oral treatment of mice with retinal detachment with Vorolanib (40mg/kg) did not result in a decrease in retinal and outer nuclear layer (ONL) thickness, indicating a protective effect against photoreceptor degeneration[7].
References:
[1]Fabre M, Mateo L, Lamaa D, et al. Recent advances in age-related macular degeneration therapies[J]. Molecules, 2022, 27(16): 5089.
[2]Liang C, Yuan X, Shen Z, et al. Vorolanib, a novel tyrosine receptor kinase receptor inhibitor with potent preclinical anti-angiogenic and anti-tumor activity[J]. Molecular Therapy-Oncolytics, 2022, 24: 577-584.
[3]Xu L, Huang J, Liu J, et al. CM082 enhances the efficacy of chemotherapeutic drugs by inhibiting the drug efflux function of ABCG2[J]. Molecular Therapy-Oncolytics, 2020, 16: 100-110.
[4]Dan H, Lei X, Huang X, et al. CM082, a novel VEGF receptor tyrosine kinase inhibitor, can inhibit angiogenesis in vitro and in vivo[J]. Microvascular Research, 2021, 136: 104146.
[5]Zhang K, Wang L, Wei A, et al. CM082, a novel angiogenesis inhibitor, enhances the antitumor activity of gefitinib on epidermal growth factor receptor mutant non‐small cell lung cancer in vitro and in vivo[J]. Thoracic cancer, 2020, 11(6): 1566-1577.
[6]Ren C, Shi H, Jiang J, et al. The effect of CM082, an oral tyrosine kinase inhibitor, on experimental choroidal neovascularization in rats[J]. Journal of Ophthalmology, 2017, 2017(1): 6145651.
[7]Howard-Sparks M, Saim S, Farjo R, et al. Neuroprotective effect of tyrosine kinase inhibitor vorolanib in a mouse model of retinal detachment[J]. Investigative Ophthalmology & Visual Science, 2023, 64(8): 2829-2829.
| Cell experiment [1]: | |
Cell lines | Human umbilical vein endothelial cells (HUVECs) |
Preparation Method | HUVECs were seeded at a density of 2×103 cells per well in a 96-well plate. After 24h, cells were incubated with or without 0.1%DMSO and 10μM Vorolanib, respectively. Thirty minutes later, cells were treated with or without a final concentration of 50ng/ml recombinant human VEGF165 for 48h. Then, the cell viability was measured using the CCK8 method. |
Reaction Conditions | 10µM; 48h |
Applications | 0.1% DMSO had no effect on HUVEC proliferation, 50 ng/ml rHuVEGF165 induced HUVEC proliferation, and 10μM Vorolanib inhibited HUVEC proliferation. |
| Animal experiment [2]: | |
Animal models | Female BALB/c nude mice |
Preparation Method | H3255 cells were subcutaneously injected into the right flank of the mice. When the tumor volume reached approximately 100 mm3, the mice were randomly assigned to six groups and treated with DMSO, Vorolanib (80mg/kg b.i.d.), Vorolanib (160mg/kg b.i.d.), sunitinib (50mg/kg q.d.), gefitinib (10 mg/kg q.d.), and gefitinib (10 mg/kg q.d.) combined with Vorolanib (80mg/kg b.i.d.), respectively. Bodyweight and tumor volume of the mice were measured every three days for 21 days. |
Dosage form | 80、160mg/kg; s.c. |
Applications | Vorolanib slowed tumor growth, and significantly inhibited the phosphorylation of ERK1/2 and AKT. |
References: [1]Dan H, Lei X, Huang X, et al. CM082, a novel VEGF receptor tyrosine kinase inhibitor, can inhibit angiogenesis in vitro and in vivo[J]. Microvascular Research, 2021, 136: 104146. [2]Zhang K, Wang L, Wei A, et al. CM082, a novel angiogenesis inhibitor, enhances the antitumor activity of gefitinib on epidermal growth factor receptor mutant non‐small cell lung cancer in vitro and in vivo[J]. Thoracic cancer, 2020, 11(6): 1566-1577. | |
| Cas No. | 1013920-15-4 | SDF | |
| المرادفات | CM082; X-82 | ||
| Canonical SMILES | O=C1/C(C2=CC(F)=CC=C2N1)=C/C(NC(C)=C3C(N[C@@H]4CN(C(N(C)C)=O)CC4)=O)=C3C | ||
| Formula | C23H26FN5O3 | M.Wt | 439.48 |
| الذوبان | DMSO: 27 mg/mL (61.44 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.2754 mL | 11.3771 mL | 22.7542 mL |
| 5 mM | 0.4551 mL | 2.2754 mL | 4.5508 mL |
| 10 mM | 0.2275 mL | 1.1377 mL | 2.2754 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >98.00%
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Average Rating: 5 (Based on Reviews and 36 reference(s) in Google Scholar.)
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