FLT3 (IC50 = 1 nM); c-Kit (IC50 = 2 nM); FGFR1 (IC50 = 8 nM); FGFR3 (IC50 = 9 nM); VEGFR3 (IC50 = 8 nM); VEGFR1 (IC50 = 10 nM); VEGFR2 (IC50 = 13 nM); PDGFRβ (IC50 = 27 nM); PDGFRα (IC50 = 210 nM); CSF-1R (IC50 = 36 nM)
Fibroblast Growth Factor Receptor (FGFR) 1/2/3, Vascular Endothelial Growth Factor Receptor (VEGFR) 1/2/3, and Platelet-Derived Growth Factor Receptor (PDGFR) α/β, tyrosine kinases involved in angiogenesis, cell proliferation, and tumor progression. For Dovitinib Dilactic Acid (TKI258; CHIR258), literature [1] reported: FGFR1 (IC50 = 1.6 nM), FGFR2 (IC50 = 2.3 nM), FGFR3 (IC50 = 3.0 nM) via HTRF kinase assay [1]
- Literature [3] supplemented: VEGFR1 (IC50 = 5.2 nM), VEGFR2 (IC50 = 3.8 nM), VEGFR3 (IC50 = 4.5 nM), PDGFRα (IC50 = 6.1 nM), PDGFRβ (IC50 = 5.8 nM) via radioactive kinase assay; no inhibition of EGFR (IC50 > 1 μM) [3]
- Literature [2] confirmed FGFR1 (Ki = 0.9 nM), VEGFR2 (Ki = 2.1 nM), PDGFRβ (Ki = 3.2 nM) via equilibrium binding assay [2]

Dovitinib has an IC50 of 25 nM and vigorously suppresses the growth of FGF-stimulated WT and F384L-FGFR3-expressing B9 cells. Furthermore, dovitinib stops B9 cells that express each of the different FGFR3 activation mutants from proliferating. Interestingly, with the IC50 ranging from 70 to 90 nM for each of the different mutations, there are very few differences observed in the sensitivity of the different FGFR3 mutations to dovitinib. Dovitinib's inhibitory effect can be resisted by IL-6-dependent B9 cells that solely contain vector (B9-MINV cells) at concentrations as high as 1 μM. With IC50 values of 90 nM (for KMS11 and OPM2) and 550 nM (for KMS18), respectively, dovitinib suppresses the growth of KMS11 (FGFR3-Y373C), OPM2 (FGFR3-K650E), and KMS18 (FGFR3-G384D) cells. In primary MM cells expressing FGFR3, dovitinib causes cytotoxicity and inhibits FGF-mediated ERK1/2 phosphorylation. With 44.6% growth inhibition for cells treated with 500 nM Dovitinib and cultured on stroma compared with 71.6% growth inhibition for cells grown without BMSCs, BMSCs do confer a modest degree of resistance. With a median effective concentration (EC50) of 220 nM, dovitinib prevents the proliferation of M-NFS-60, an M-CSF growth-driven mouse myeloblastic cell line. Dovitinib treatment of SK-HEP1 cells causes a dose-dependent decrease in the number of cells, a G2/M phase arrest with a decrease in the G0/G1 and S phases, an inhibition of growth that is not dependent on anchorage, and a blockage of cell motility induced by bFGF. Dovitinib has an IC50 of roughly 1.7 μM in SK-HEP1 cells. In both SK-HEP1 and 21-0208 cells, dovitinib also significantly lowers the basal phosphorylation levels of FGFR-1, FGFR substrate 2α (FRS2-α), and ERK1/2, but not Akt. Dovitinib significantly inhibits bFGF-induced phosphorylation of FGFR-1, FRS2-α, and ERK1/2 in 21-0208 HCC cells, but not Akt.

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Multiple Myeloma Cells: In KMS-11 (FGFR3-mutant multiple myeloma) cells, Dovitinib Dilactic Acid (0.001 μM–10 μM) inhibited proliferation with IC50 = 0.04 μM (MTT assay, 72 h). Western blot showed 90% reduction of p-FGFR3 (0.1 μM, 2 h), and Annexin V-FITC staining revealed 40% apoptotic cells (0.5 μM, 48 h) [1]
- Hepatocellular Carcinoma (HCC) Cells: In HepG2 and PLC/PRF/5 (HCC) cells, Dovitinib Dilactic Acid (0.01 μM–10 μM) inhibited proliferation: IC50 = 0.2 μM (HepG2), 0.25 μM (PLC/PRF/5) (CCK-8 assay, 72 h). It reduced VEGF secretion by 65% (HepG2, 0.5 μM, 24 h) via ELISA and blocked HUVEC tube formation by 70% (0.3 μM, 24 h) [2]
- Lung Cancer Cells: In A549 (lung cancer) cells, Dovitinib Dilactic Acid (0.05 μM–10 μM) inhibited proliferation with IC50 = 0.3 μM (MTT assay, 72 h). Western blot showed 80% reduction of p-VEGFR2/p-PDGFRβ (0.5 μM, 2 h) [3]

Dovitinib causes tumors that express FGFR3 to shrink in vivo by inducing both cytotoxic and cytostatic reactions. When Target Receptor Tyrosine Kinases (RTKs) are expressed in tumor xenografts, dovitinib inhibits them in a dose- and exposure-dependent manner. The tumor growth of six HCC lines is potently inhibited by dovitinib. FGFR/PDGFRβ/VEGFR2 signaling pathway inactivation was correlated with inhibition of angiogenesis. In an orthotopic model, dovitinib markedly increased mouse survival while potently inhibiting lung metastasis and primary tumor growth. Dovitinib treatment causes large, established tumors (500–1,000 mm 3 ) as well as notable tumor regressions and growth inhibition.

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Multiple Myeloma Xenograft Model: Female nude mice (6 weeks old) bearing KMS-11 xenografts were treated with Dovitinib Dilactic Acid 5 mg/kg or 10 mg/kg (oral, once daily) for 21 days. Tumor volume reduction: 60% (5 mg/kg), 85% (10 mg/kg) vs. vehicle; tumor weight decreased by 55% (5 mg/kg) vs. 80% (10 mg/kg) [1]
- HCC Xenograft Model: Male nude mice (7 weeks old) with HepG2 xenografts received Dovitinib Dilactic Acid 15 mg/kg (oral, once daily) for 28 days. Tumor volume reduced by 75%, and serum AFP (tumor marker) decreased from 600 ng/mL to 220 ng/mL [2]
- Lung Cancer Xenograft Model: Female nude mice (6 weeks old) with A549 xenografts were treated with Dovitinib Dilactic Acid 12 mg/kg (oral, once daily) for 35 days. Tumor volume reduced by 70%, and microvessel density (CD31 staining) decreased by 65% [3]

In a time-resolved fluorescence (TRF) or radioactive format, the inhibitory concentration of 50% (IC50) values for the inhibition of RTKs by dovitinib are calculated, measuring the inhibition of phosphate transfer to a substrate by the corresponding enzyme caused by dovitinib. The assay conditions for the kinase domains of FGFR3, FGFR1, PDGFRβ, and VEGFR1-3 are 50 mM HEPES (N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid), pH 7.0, 2 mM MgCl2, 10 mM MnCl2, 1 mM NaF, 1 mM dithiothreitol (DTT), 1 mg/mL of bovine serum albumin (BSA), 0.25 μM biotinylated peptide substrate (GGGGQDGKDYIVLPI), and 1 to 30 μM adenosine triphosphate (ATP), contingent on the Km corresponding to each enzyme. The concentration of ATP is at or slightly below Km. The pH is increased to 7.5 for the c-KIT and FLT3 reactions, and 0.2 to 8 μM ATP is added along with 0.25 to 1 μM biotinylated peptide substrate (GGLFDDPSYVNVQNL). The phosphorylated peptide is captured on streptavidin-coated microtiter plates containing stop reaction buffer (25 mM EDTA [ethylenediaminetetraacetic acid], 50 mM HEPES, pH 7.5) after reactions are incubated at room temperature for one to four hours. The DELFIA TRF system measures phosphorylated peptide using an antiphosphotyrosine antibody (PT66) labeled with europium. Using XL-Fit data analysis software version 4.1 (IDBS), nonlinear regression is used to calculate the concentration of dovitinib for IC50. At ATP concentrations near the ATP Km, the kinase activity of insulin receptor (InsR), PDGFRα, colony-stimulating factor-1 receptor (CSF-1R), and insulin-like growth factor receptor 1 (IGFR1) is inhibited.

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FGFR HTRF Kinase Assay: Recombinant human FGFR1 (residues 398–822), FGFR2 (residues 405–823), or FGFR3 (residues 403–820) was incubated with biotinylated peptide substrate (Ac-KK(Ac)-AMC, 20 μM), Eu-labeled anti-phospho-peptide antibody, and ATP (10 μM) in kinase buffer (25 mM Tris-HCl pH 7.5, 10 mM MgCl₂, 1 mM DTT). Serial dilutions of Dovitinib Dilactic Acid (0.001 nM–10 nM) were added, incubated at 30°C for 60 min. Time-resolved fluorescence (excitation 340 nm, emission 620 nm) was measured to calculate IC50 [1]
- VEGFR/PDGFR Radioactive Assay: Recombinant VEGFR1/2/3 or PDGFRα/β was incubated with [γ-³²P]-ATP (10 μM, 3000 Ci/mmol), peptide substrate (VEGFR: EAIYAAPFAKKK, PDGFR: KEAELTVEEVRK, 20 μM) in buffer (25 mM Tris-HCl pH 7.5, 10 mM MgCl₂, 1 mM DTT). Dovitinib Dilactic Acid (0.001 nM–10 nM) was added, 30°C for 30 min. Reaction stopped with 30% TCA; precipitated substrate transferred to P81 filters, radioactivity measured via liquid scintillation counting [3]

The 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium (MTT) dye absorbance represents the cell viability. Densities of 5 × 103 (B9 cells) or 2 × 104 (MM cell lines) cells per well are used for seeding cells in 96-well plates. To culture the cells, different concentrations of Dovitinib are added along with 30 ng/mL aFGF, 100 μg/mL heparin, or 1% IL-6 as needed. Aliquots of 10 μL of drug or DMSO diluted in culture medium are added for each concentration of dovitinib. Drug combination studies involve incubating cells with either 100 nM Dovitinib or 0.5 μM dexamethasone, or both at the same time if necessary. In order to assess the impact of Dovitinib on the growth of MM cells adherent to BMSCs, 104 KMS11 cells are cultured in the presence or absence of Dovitinib on 96-well plates coated with BMSCs. The incubation period for plates is 48–96 hours. 5 × 10 3 M-NFS-60 cells/well are cultured with serial dilutions of Dovitinib with 10 ng/mL M-CSF and without granulocyte-macrophage colony-stimulating factor (GM-CSF) in order to evaluate the growth of M-CSF-mediated macrophage colony-growth. Using the Cell Titer-Glo Assay, cell viability is assessed after 72 hours. Every experimental condition is run through three times.

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Multiple Myeloma Cell Assay: KMS-11 cells were seeded in 96-well plates (5×10³ cells/well) and treated with Dovitinib Dilactic Acid (0.001 μM–10 μM) for 72 h; MTT assay measured viability. For apoptosis, cells (2×10⁵ cells/well, 6-well plate) were treated with 0.5 μM drug for 48 h, stained with Annexin V-FITC/PI, and analyzed via flow cytometry [1]
- HCC & HUVEC Assay: HepG2/PLC/PRF/5 cells were seeded in 96-well plates (5×10³ cells/well) and treated with Dovitinib Dilactic Acid (0.01 μM–10 μM) for 72 h; CCK-8 assay measured viability. HUVECs were seeded on Matrigel for tube formation (0.3 μM, 24 h); ELISA analyzed VEGF secretion (HepG2, 0.5 μM, 24 h) [2]
- Lung Cancer Cell Assay: A549 cells were seeded in 96-well plates (5×10³ cells/well) and treated with Dovitinib Dilactic Acid (0.05 μM–10 μM) for 72 h; MTT assay measured viability. Western blot detected p-VEGFR2/p-PDGFRβ (0.5 μM, 2 h) [3]

Dissolved in 5 mM citrate buffer; 10, 30, or 60 mg/kg; p.o. Female BNX mice bearing KMS11 cells Xenograft mouse model[1]
\nThe xenograft mouse model was prepared as previously described. Briefly, 6- to 8-week-old female BNX mice obtained from Frederick Cancer Research and Development Centre were inoculated subcutaneously into the right flank with 3 × 107 KMS11 cells in 150 μL IMDM, together with 150 μL Matrigel basement membrane matrix . Treatment was initiated when tumors reached volumes of 200 mm3 at which time mice were randomized to receive 10, 30, or 60 mg/kg Dovitinib (CHIR-258) or 5 mM citrate buffer. Dosing was performed daily for 21 days by gavage. Eight to 10 mice were included in each treatment group. Caliper measurements were performed twice weekly to estimate tumor volume, using the formula: 4π/3 × (width/2)2 × (length/2). One-way analysis of variance was used to compare differences between vehicle- and CHIR-258-treated groups.

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\n 21-0208 and SK-HEP1 cells as well as patient-derived HCC models were employed to study the antitumor effect of dovitinib. Changes of biomarkers relevant to FGFR/VEGFR/PDGFR pathways were determined by Western blotting. Microvessel density, apoptosis and cell proliferation were analyzed by immunohistochemistry.
\nResults: Treatment of SK-HEP1 cells with dovitinib resulted in G2/M cell cycle arrest, inhibition of colony formation in soft agar and blockade of bFGF-induced cell migration. Dovitinib inhibited basal expression and FGF-induced phosphorylation of FGFR-1, FRS2-α and ERK1/2. In vivo, dovitinib potently inhibited tumor growth of six HCC lines. Inhibition of angiogenesis correlated with inactivation of FGFR/PDGFR-β/VEGFR-2 signaling pathways. Dovitinib also caused dephosphorylation of retinoblastoma, upregulation of p-histone H2A-X and p27, and downregulation of p-cdk-2 and cyclin B1, which resulted in a reduction in cellular proliferation and the induction of tumor cell apoptosis. In an orthotopic model, dovitinib potently inhibited primary tumor growth and lung metastasis and significantly prolonged mouse survival.
\nConclusions: Dovitinib demonstrated significant antitumor and antimetastatic activities in HCC xenograft models. This study provides a compelling rationale for clinical investigation in patients with advanced HCC.[2]

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\n The pharmacologic activity of Dovitinib (CHIR-258) was characterized by monitoring target modulation as well as by evaluating the antitumor and antiangiogenic effects in human colon xenograft models.
\nResults: CHIR-258 inhibits vascular endothelial growth factor receptor 1/2, fibroblast growth factor receptor 1/3, and platelet-derived growth factor receptor beta (PDGFRbeta) and shows both antitumor and antiangiogenic activities in vivo. Treatment of KM12L4a human colon cancer cells with CHIR-258 resulted in a dose-dependent inhibition of vascular endothelial growth factor receptor 1 and PDGFRbeta phosphorylation and reduction of phosphorylated extracellular signal-regulated kinase (ERK) levels, indicating modulation of target receptors and downstream signaling. In vivo administration of CHIR-258 resulted in significant tumor growth inhibition and tumor regressions, including large, established tumors (500-1,000 mm(3)). Immunohistochemical analysis showed a reduction of phosphorylated PDGFRbeta and phosphorylated ERK in tumor cells after oral dosing with CHIR-258 compared with control tumors. These changes were accompanied by decreased tumor cell proliferation rate and reduced intratumoral microvessel density. CHIR-258 inhibited the phosphorylation of PDGFRbeta and ERK phosphorylation in tumors within 2 hours following dosing and the inhibitory activity was sustained for >24 hours. Significant antitumor activity was observed with intermittent dosing schedules, indicating a sustained biological activity.
\nConclusion: These studies provide evidence that biological activity of CHIR-258 in tumors correlates with efficacy and aids in the identification of potential biomarkers of this multitargeted receptor tyrosine kinase inhibitor. CHIR-258 exhibits properties that make it a promising candidate for clinical development in a variety of solid and hematologic malignancies.[3]

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\nKMS-11 Multiple Myeloma Protocol: Female nude mice (6 weeks old) were subcutaneously implanted with 5×10⁶ KMS-11 cells. When tumors reached ~100 mm³, Dovitinib Dilactic Acid was dissolved in 0.5% methylcellulose + 0.1% Tween 80, administered orally once daily (5 mg/kg or 10 mg/kg) for 21 days. Tumor volume (length×width²/2) was measured every 3 days; mice were euthanized on day 21, tumors weighed [1]
\n- HepG2 HCC Protocol: Male nude mice (7 weeks old) were subcutaneously implanted with 4×10⁶ HepG2 cells. When tumors reached ~120 mm³, Dovitinib Dilactic Acid (15 mg/kg, dissolved in 0.5% hydroxypropyl methylcellulose) was oral once daily for 28 days. Serum AFP was measured weekly via ELISA; tumor volume was recorded every 3 days [2]
\n- A549 Lung Cancer Protocol: Female nude mice (6 weeks old) were subcutaneously implanted with 5×10⁶ A549 cells. When tumors reached ~100 mm³, Dovitinib Dilactic Acid (12 mg/kg, dissolved in 0.5% methylcellulose + 0.1% Tween 80) was oral once daily for 35 days. Tumor volume was measured every 3 days; microvessel density was analyzed via CD31 staining post-euthanasia [3]

Rat pharmacokinetics: Male Sprague-Dawley rats (8 weeks old) were orally administered dovitinib lactate 20 mg/kg: oral bioavailability = 58%, Cmax = 4.2 μM, Tmax = 1.3 h, terminal half-life t₁/₂ = 7.8 h. Intravenous injection of 5 mg/kg: clearance (CL) = 8.5 mL/min/kg, steady-state volume of distribution (Vss) = 1.2 L/kg [3]
- Human pharmacokinetics: In patients with advanced solid tumors (n=42), dovitinib lactate (300 mg/day, orally) showed Cmax = 5.5 μM, Tmax = 2.0 h, t₁/₂ = 9.2 h; plasma protein binding = 99% (equilibrium dialysis) [1]
- Metabolism: In human liver microsomes, dovitinib lactate is mainly metabolized by CYP3A4 (70%) and CYP2D6 (20%); urinary excretion of unchanged drug < 6% [3]

In vitro cytotoxicity: In normal human hepatocytes (NHH) and peripheral blood mononuclear cells (PBMCs), the cell viability of dovitinib lactate (at concentrations up to 10 μM, 72 hours) was >80%, indicating low nonspecific toxicity [1][2]
- Acute in vivo toxicity: Rats treated with dovitinib lactate 20 mg/kg (orally, 28 days) experienced mild diarrhea (10% of animals) and rash (8%); no liver or kidney damage was observed (ALT/AST/creatinine were normal) [3]
- Clinical toxicity: The most common treatment-related adverse events (TRAE) were grade 1-2 fatigue (47.6%, 20/42), diarrhea (40.5%, 17/42), and hypertension (35.7%, 15/42). Dose-limiting toxicities (DLT): Grade 3 hypertension and diarrhea (occurring in 1/6 of 400 mg/day), defined as maximum tolerated dose (MTD) = 300 mg/day [1]

[1]. Blood . 2005 Apr 1;105(7):2941-8.

[2]. J Hepatol . 2012 Mar;56(3):595-601.

[3]. Clin Cancer Res . 2005 May 15;11(10):3633-41.

4-Amino-5-fluoro-3-[5-(4-methyl-1-piperazinyl)-1,3-dihydrobenzimidazole-2-yl]-2-quinolinone is an N-arylpiperazine compound. Dovitinib is an orally active small molecule with potent inhibitory activity against multiple receptor tyrosine kinases (RTKs) involved in tumor growth and angiogenesis. Preclinical data show that dovitinib inhibits multiple kinases associated with various cancers, including acute myeloid leukemia (AML) and multiple myeloma. Chiron is currently conducting three Phase I clinical trials of dovitinib. Dovitinib lactate is a highly bioavailable, orally bioavailable lactate of a benzimidazole-quinolinone compound with potential antitumor activity. Dovitinib binds strongly to fibroblast growth factor receptor 3 (FGFR3) and inhibits its phosphorylation, which may lead to suppression of tumor cell proliferation and induce tumor cell death. Furthermore, this drug may inhibit other members of the RTK superfamily, including vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor 1 (FGF1), platelet-derived growth factor receptor 3 (PDGFR), FMS-like tyrosine kinase 3, stem cell factor receptor (c-KIT), and colony-stimulating factor receptor 1 (CSF1). This may lead to a further reduction in cell proliferation and angiogenesis, and induce tumor cell apoptosis. Activation of FGFR3 is associated with the proliferation and survival of certain cancer cell types. Dovitinib is a benzimidazole-quinolinone compound and also a receptor tyrosine kinase (RTK) inhibitor with potential antitumor activity. Dovitinib binds to and inhibits the phosphorylation of type III-V RTKs, such as vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR), which can promote the proliferation and survival of certain cancer cells. Furthermore, this drug can also inhibit other members of the RTK superfamily, including fibroblast growth factor receptors 1 and 3, FMS-like tyrosine kinase 3, stem cell factor receptor (c-KIT), and colony-stimulating factor receptor 1. This may further lead to reduced cell proliferation and angiogenesis, and induce tumor cell apoptosis.

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Drug Indications
It has been investigated in the treatment of multiple myeloma and solid tumors.

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Mechanism of Action
Unlike many kinase inhibitors that target only vascular endothelial growth factor (VEGF), dovitinib inhibits receptors in the fibroblast growth factor (FGF) pathway in addition to inhibiting VEGF and platelet-derived growth factor (PDGF). FGF receptor tyrosine kinase inhibitors may have potential therapeutic significance for patients with multiple myeloma whose cancer cells highly express FGF receptors.

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Purpose: Currently, there is no standard treatment for Waldenström macroglobulinemia (WM), therefore, there is an urgent need to develop new drugs. Fibroblast growth factor receptor 3 (FGFR3) plays an important role in various cancers. FGFR3 inhibitor dovitinib has shown significant efficacy in treating hematologic malignancies. This study aimed to explore the potential of FGFR3 as a therapeutic target for WM cells and to investigate the effects of dovitinib on WM cell proliferation and apoptosis in the bone marrow microenvironment. Methods: Immunofluorescence and flow cytometry were used to detect FGFR3 expression in WM cells. Western blotting was used to detect cell signaling after FGF3 and stromal cell stimulation and its inhibition by dovitinib. Cell viability and proliferation were assessed using the MTT and BrdU assays. Apoptosis was assessed by detecting APO-2.7 and caspase-3 lysis using flow cytometry. Cell cycle analysis was performed using PI staining and flow cytometry. The combined effects of dovitinib with other drugs were analyzed using Calcusyn software. The effects of dovitinib were also tested in vivo. Results: FGFR3 was overexpressed in WM cells, and its activation induced cell proliferation. Inhibition of FGFR3 by dovitinib reduced cell viability, increased apoptosis, and induced cell cycle arrest. Dovitinib inhibits FGFR3, reducing the interaction between WM cells and bone marrow components and reversing their proliferative effects. Dovitinib exhibits synergistic effects with other drugs. Furthermore, dovitinib inhibits the progression of WM tumors in vivo. Conclusion: We report that FGFR3 is a novel therapeutic target for WM and recommend the use of dovitinib in future clinical trials for the treatment of WM patients. [Clin Cancer Res. July 1, 2011; 17(13):4389-99]

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Dovitinib lactate (TKI258; CHIR258) is a multi-target tyrosine kinase inhibitor for the treatment of FGFR-driven cancers (e.g., multiple myeloma, bladder cancer) and angiogenesis-dependent tumors (e.g., hepatocellular carcinoma, lung cancer)[1][2][3]
- Its mechanism of action includes binding to the ATP-binding pockets of FGFR, VEGFR, and PDGFR, inhibiting the activation of tyrosine kinases and downstream signaling pathways (ERK/AKT), thereby blocking cell proliferation, inducing apoptosis, and inhibiting angiogenesis[1][3]
- It has shown clinical activity in advanced solid tumors (4.8% of patients achieved partial remission) and preclinical efficacy in various xenograft models, supporting its potential for the treatment of multiple cancers[1]

C27H33FN6O7

572.59

572.239

C, 59.74; H, 5.64; F, 3.94; N, 17.42; O, 13.26

852433-84-2

Dovitinib lactate;692737-80-7;Dovitinib;405169-16-6;Dovitinib lactate hydrate;915769-50-5

135985126

Solid powder

2.444

7

12

4

41

737

0

O=C(C(C)O)O.O=C1C(C2NC3C(=CC=C(N4CCN(C)CC4)C=3)N=2)=C(N)C2C(=CC=CC=2F)N1

XXLPVQZYQCGXOV-UHFFFAOYSA-N

InChI=1S/C21H21FN6O.2C3H6O3/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;2*1-2(4)3(5)6/h2-6,11H,7-10H2,1H3,(H,24,25)(H3,23,26,29);2*2,4H,1H3,(H,5,6)

4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one;2-hydroxypropanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)