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Dovitinib (TKI258) Lactate

Oral tyrosine kinase inhibitor (TKI) against FGFR1–3, VEGFR1–3, and platelet-derived growth factor receptor (PDGFR). CAS# 915769-50-5

Dovitinib (TKI258) Lactate

2D Structure

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Dovitinib (TKI258) Lactate

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Chemical Properties of Dovitinib (TKI258) Lactate

Cas No. 915769-50-5 SDF Download SDF
PubChem ID 135611162 Appearance Powder
Formula C24H27FN6O4 M.Wt 482.51
Type of Compound N/A Storage Desiccate at -20°C
Solubility ≥168.2mg/ml in H2O
Chemical Name 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one;2-hydroxypropanoic acid;hydrate
SMILES CC(C(=O)O)O.CN1CCN(CC1)C2=CC3=C(C=C2)N=C(N3)C4=C(C5=C(C=CC=C5F)NC4=O)N.O
Standard InChIKey QDPVYZNVVQQULH-UHFFFAOYSA-N
Standard InChI InChI=1S/C21H21FN6O.C3H6O3.H2O/c1-27-7-9-28(10-8-27)12-5-6-14-16(11-12)25-20(24-14)18-19(23)17-13(22)3-2-4-15(17)26-21(18)29;1-2(4)3(5)6;/h2-6,11H,7-10H2,1H3,(H,24,25)(H3,23,26,29);2,4H,1H3,(H,5,6);1H2
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Dovitinib (TKI258) Lactate Dilution Calculator

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Dovitinib (TKI258) Lactate Molarity Calculator

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Preparing Stock Solutions of Dovitinib (TKI258) Lactate

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.0725 mL 10.3625 mL 20.725 mL 41.4499 mL 51.8124 mL
5 mM 0.4145 mL 2.0725 mL 4.145 mL 8.29 mL 10.3625 mL
10 mM 0.2072 mL 1.0362 mL 2.0725 mL 4.145 mL 5.1812 mL
50 mM 0.0414 mL 0.2072 mL 0.4145 mL 0.829 mL 1.0362 mL
100 mM 0.0207 mL 0.1036 mL 0.2072 mL 0.4145 mL 0.5181 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

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Background on Dovitinib (TKI258) Lactate

Description:

IC50: ~10 nmol/L for FGFR1–3

Fibroblast growth factor receptor 1 (FGFR1) and FGFR2 amplifications are observed in approximately 10% of breast cancers and are related to poor outcomes. Dovitinib (TKI258) is an oral tyrosine kinase inhibitor (TKI) against FGFR1–3, VEGFR1–3, and platelet-derived growth factor receptor (PDGFR).

In vitro: Dovitinib decreased the concentrations of pFRS2 and pERK/MAPK in a dose-dependent manner in FGFR1 amplified and FGFR2 amplified cell lines. The IC50 for cell growth inhibition was 190 and 180 nmol/L in MDA-MB-134 and SUM52, respectively. Conversely, IC50 values were more than 2,000 nmol/L in the 11 breast cancer cell lines that had neither FGFR1 nor FGFR2 amplification [1].

In vivo: In vivo model (HBCx-2 breast cancer primary xenograft, with 8 FGFR1 gene copies), dovitinib prevented tumor growth at the 30 mg/kg dose and caused tumor regression at the 50 mg/kg dose. Similarly, dovitinib caused tumor regression in HBCx-3 xenografts when administered at a dose of 40 mg/kg daily until day 35 [1].

Clinical trial: Eighty-one patients were enrolled in the trial. Unconfirmed response or stable disease for over 6 months was observed in 5 and 1 patient(s) with FGFR1-amplified/HR-positive and FGFR1-nonamplified/HR-positive breast cancer. When qPCR-identified amplifications in FGFR1, FGFR2, or FGF3 were grouped to define an FGF pathway–amplified breast cancer in HR-positive patients, the mean reduction in target lesions was 21.1% compared with a 12.0% increase in patients that did not present with FGF pathway–amplified breast cancer [1].

Reference:
[1] André F, Bachelot T, Campone M, Dalenc F, Perez-Garcia JM, Hurvitz SA, Turner N, Rugo H, Smith JW, Deudon S, Shi M, Zhang Y, Kay A, Porta DG, Yovine A, Baselga J.  Targeting FGFR with dovitinib (TKI258): preclinical and clinical data in breast cancer. Clin Cancer Res. 2013 Jul 1;19(13):3693-702.

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