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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Telatinib mesylate (also known as Bay 57-9352 mesylate) is a potent and orally bioactive VEGFR2, VEGFR3, PDGFα, and c-Kit inhibitor with potential anticancer activity. Its IC50 values are 6 nM, 4 nM, 15 nM, and 1 nM for VEGFR2, VEGFR3, PDGFα, and c-Kit, respectively.
Targets |
VEGFR2 (IC50 = 6 nM); VEGFR3 (IC50 = 4 nM); PDGFRα (IC50 = 15 nM); c-Kit (IC50 = 1 nM)
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ln Vitro |
Telatinib inhibits the activity of the ATP-binding cassette G2 (ABCG2) efflux transporter, which increases the anticancer activity of ABCG2 substrate anticancer drugs. While Telatinib by itself has no discernible effect on drug-sensitive and drug-resistant cell lines, co-incubating ABCG2-overexpressing drug-resistant cell lines with Telatinib and ABCG2 substrate anticancer medications significantly lowers cellular viability. In cell lines that overexpress ABCG2, telibiba at 1 μM has no discernible effect on ABCG2 expression. In cell lines that overexpress ABCG2, telibib at 1 μM dramatically increases the intracellular accumulation of [3H]-mitoxantrone (MX)[2].
Telatinib significantly lowers the rate of [3H]-MX efflux from cells overexpressing ABCG2 at 1 μM. Moreover, in membrane vesicles overexpressing ABCG2, Telatinib strongly inhibits ABCG2-mediated transport of [3H]-E₂17βG[2].
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ln Vivo |
Telatinib (15 mg/kg; oral dministration; every 2nd and 3rd day; total 12 times; male athymic NCR (nu/nu) nude mice) with Doxorubicin (1.8 mg/kg) significantly reduces the tumor size and growth rate of tumors overexpressing ABCG2[2].
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Enzyme Assay |
In the membrane of High Five insect cells, the vanadate (Vi)-sensitive ATPase activity of ABCG2 is quantified. Membranes (2 μg/0.06 mL) are briefly incubated for 5 min at 37°C in ATPase assay buffer, either with or without 0.4 mM vanadate. Following this, they are incubated for an additional 5 min at 37°C with different concentrations of telatinib. Incorporating 4 mM Mg-ATP initiates the ATPase reaction. Reactions are halted by adding 0.05 mL of 10% SDS solution after 10 minutes of incubation at 37°C. A measurement is made of the released inorganic phosphate.
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Cell Assay |
Telatinib exhibits low affinity towards the Tie-2 receptor, the Raf kinase pathway, the fibroblast growth factor receptor (FGFR) family, and the epidermal growth factor receptor family. Telatinib is metabolized by uridine diphosphate glucuronosyltransferase 1A4 (UGT1A4) and a number of cytochrome P450 (CYP) isoforms, including CYP3A4/3A5, CYP2C8, CYP2C9, and CYP2C19. In humans, the primary biotransformation pathway for telatinib is the formation of its N-glucuronides. Telatinib is a weak substrate of the adenosine triphosphate binding cassette (ABC) B1 (ABCB1) transporter, according to in vitro research. Telatinib at 1 μM significantly enhances the intracellular accumulation of [3H]-mitoxantrone (MX) in ABCG2-overexpressing cell lines. In addition, telatinib at 1 μM significantly reduces the rate of [3H]-MX efflux from ABCG2-overexpressing cells. Furthermore, telatinib significantly inhibits ABCG2-mediated transport of [3H]-E217βG in ABCG2 overexpressing membrane vesicles. In cell lines that overexpress ABCG2, telibiba at 1 μM dramatically increases the intracellular accumulation of [3H]-mitoxantrone (MX). Furthermore, telatinib at 1 μM dramatically lowers the rate at which ABCG2-overexpressing cells efflux [3H]-MX. Additionally, in membrane vesicles overexpressing ABCG2, telatinib significantly inhibits ABCG2-mediated transport of [3H]-E217βG.
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Animal Protocol |
Male athymic NCR (nu/nu) nude mice (13-15 g, age 4-5 weeks) injected with H460 and H460/MX20 cells[2]
15 mg/kg Oral dministration; every 2nd and 3rd day; total 12 times |
References |
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Molecular Formula |
C₂₁H₂₀CLN₅O₆S
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Molecular Weight |
505.93
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Exact Mass |
505.0822822
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CAS # |
332013-26-0
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Related CAS # |
Telatinib;332012-40-5
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Appearance |
Solid
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SMILES |
CNC(=O)C1=NC=CC(=C1)COC2=NN=C(C3=C2OC=C3)NC4=CC=C(C=C4)Cl.CS(=O)(=O)O
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InChi Key |
LCMLACPWPXITHP-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C20H16ClN5O3.CH4O3S/c1-22-19(27)16-10-12(6-8-23-16)11-29-20-17-15(7-9-28-17)18(25-26-20)24-14-4-2-13(21)3-5-14;1-5(2,3)4/h2-10H,11H2,1H3,(H,22,27)(H,24,25);1H3,(H,2,3,4)
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Chemical Name |
4-[[4-(4-chloroanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-N-methylpyridine-2-carboxamide;methanesulfonic acid
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Synonyms |
BAY-57-9352; BAY 57-9352; BAY 57-9352; BAY57-9352
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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: ~250 mg/mL (~494.1 mM)
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.9766 mL | 9.8828 mL | 19.7656 mL | |
5 mM | 0.3953 mL | 1.9766 mL | 3.9531 mL | |
10 mM | 0.1977 mL | 0.9883 mL | 1.9766 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 |
NCT03175497 | Completed | Drug: Telatinib Mesylate | Solid Tumor, Adult | Taizhou EOC Pharma Co., Ltd. | July 25, 2017 | Phase 1 |
Br J Cancer. 2008 Nov 4; 99(10): 1579–1585. td> |
Geometric mean telatinib plasma concentration vs time profiles on day 14 of cycle 1. Br J Cancer. 2008 Nov 4; 99(10): 1579–1585. td> |