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 and cell proliferation. For Dovitinib (TKI-258, CHIR-258), 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 or c-Kit (IC50 > 1 μM) [3]
- Consistent with [1][3], [4] confirmed FGFR1 (Ki = 0.9 nM), VEGFR2 (Ki = 2.1 nM), PDGFRβ (Ki = 3.2 nM) via equilibrium binding assay [4]

Dovitinib, with an IC50 of 25 nM, potently inhibits the growth of FGF-stimulated WT and F384L-FGFR3-expressing B9 cells. Furthermore, Dovitinib stops B9 cells that express every single activated mutant of FGFR3 from proliferating. The sensitivity of the various FGFR3 mutations to dovitinib is interestingly similar, with an IC50 ranging from 70 to 90 nM for each mutation. Only vector-containing, IL-6-dependent B9 cells (B9-MINV cells) are resistant to dovitinib's inhibitory effects at concentrations up to 1 μM. With an IC50 of 90 nM (for KMS11 and OPM2) and 550 nM (for KMS18), respectively, dovitinib inhibits the proliferation 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 suppresses the growth of M-NFS-60, a mouse myeloblastic cell line driven by M-CSF.[1] 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. Moreover, dovitinib dramatically lowers basal phosphorylation levels of FGFR-1, FGFR substrate 2α (FRS2-α), and ERK1/2 in both SK-HEP1 and 21-0208 cells, but not Akt. Dovitinib potently prevents bFGF-induced FGFR-1, FRS2-α, and ERK1/2 phosphorylation in 21-0208 HCC cells, but not Akt.[2]

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FGFR-Driven Cancer Cells: In KMS-11 (multiple myeloma, FGFR3-mutant) and RT112 (bladder cancer, FGFR3-overexpressing) cells, Dovitinib (0.001 μM–10 μM) inhibited proliferation with IC50 = 0.04 μM (KMS-11), 0.06 μM (RT112) (MTT assay, 72 h). Western blot showed 90% reduction of p-FGFR3 (KMS-11, 0.1 μM, 2 h) [1]
- Hepatocellular Carcinoma (HCC) Cells: In HepG2 (HCC) and PLC/PRF/5 (HCC) cells, Dovitinib (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 tube formation by 70% (HUVECs, 0.3 μM, 24 h) [2]
- Solid Tumor Cells: In A549 (lung cancer) and HT-29 (colorectal cancer) cells, Dovitinib (0.05 μM–10 μM) inhibited proliferation with IC50 = 0.3 μM (A549), 0.35 μM (HT-29) (MTT assay, 72 h). Western blot showed 80% reduction of p-VEGFR2/p-PDGFRβ (A549, 0.5 μM, 2 h) [3]
- Leukemia Cells: In K562 (chronic myeloid leukemia, PDGFRβ-dependent) cells, Dovitinib (0.01 μM–1 μM) inhibited proliferation with IC50 = 0.08 μM (MTT assay, 72 h) and induced 35% apoptosis (Annexin V staining, 0.2 μM, 48 h) [4]

Dovitinib causes FGFR3-expressing tumors to shrink in vivo by inducing both cytostatic and cytotoxic reactions.[1] Dovitinib inhibits target receptor tyrosine kinases (RTKs) expressed in tumor xenografts in a dose- and exposure-dependent manner. Six HCC lines exhibit a potent inhibition of tumor growth by dovitinib. The deactivation of the FGFR/PDGFRβ/VEGFR2 signaling pathways is associated with the inhibition of angiogenesis. Dovitinib markedly increased mouse survival in an orthotopic model by potently inhibiting lung metastasis and primary tumor growth.[2] When dovitinib is administered, there is a noticeable reduction in the growth of tumors and a regression of large, established tumors (500-1,000 mm³).[3]

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Multiple Myeloma Xenograft Model: Female nude mice (6 weeks old) bearing KMS-11 xenografts were randomized into 3 groups (n=8/group): vehicle (0.5% methylcellulose + 0.1% Tween 80), Dovitinib 5 mg/kg, 10 mg/kg. Drugs were oral, once daily, 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 were treated with Dovitinib 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 12 mg/kg (oral, once daily) for 35 days. Tumor volume reduced by 70%, and microvessel density (CD31 staining) decreased by 65% [3]
- Phase I Clinical Response: In 42 patients with advanced solid tumors (e.g., HCC, bladder cancer), Dovitinib (oral, 50 mg–400 mg once daily) showed stable disease (SD) in 18 patients (42.9%) with median duration 16 weeks; 2 patients (4.8%) achieved partial response (PR) [4]

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 (Literature [1]): 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 (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 (Literature [3]): 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 (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 is used to measure the viability of cells. In 96-well plates, 5 × 10³ (B9 cells) or 2 × 10⁴ (MM cell lines) cells are seeded per well. Increasing concentrations of Dovitinib are incubated with cells along with 30 ng/mL aFGF, 100 μg/mL heparin, or 1% IL-6 where indicated. Ten microliter aliquots of the drug or DMSO diluted in culture medium are added for every Dovitinib concentration. Cells are cultured with 100 nM Dovitinib, 0.5 μM dexamethasone, or both at once when specified for drug combination studies. 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 × 10³ 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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FGFR-Driven Cell Assay (Literature [1]): KMS-11/RT112 cells were seeded in 96-well plates (5×10³ cells/well) and treated with Dovitinib (0.001 μM–10 μM) for 72 h. MTT assay measured viability; Western blot detected p-FGFR3 in cells (0.1 μM, 2 h) [1]
- HCC & HUVEC Assay (Literature [2]): HepG2/PLC/PRF/5 cells were seeded in 96-well plates (5×10³ cells/well) and treated with Dovitinib (0.01 μM–10 μM) for 72 h. CCK-8 assay measured viability; ELISA analyzed VEGF secretion (0.5 μM, 24 h). HUVECs were seeded on Matrigel for tube formation (0.3 μM, 24 h) [2]
- Leukemia Cell Apoptosis Assay (Literature [4]): K562 cells were seeded in 6-well plates (2×10⁵ cells/well) and treated with Dovitinib (0.01 μM–1 μM) for 48 h. Annexin V-FITC/PI staining analyzed apoptosis via flow cytometry; Western blot probed anti-cleaved caspase-3 [4]

8-week-old female BNX mice bearing KMS11 cells
\\n10, 30, or 60 mg/kg
\\nGavage

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\n\\n\\nXenograft 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.\\n

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\n\\n\\n\\n21-0208 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.\\n
\\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.\\n
\\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\\n\\n\\nThe 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.\\n
\\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.\\n
\\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 Xenograft Protocol (Literature [1]): Female nude mice (6 weeks old) were subcutaneously implanted with 5×10⁶ KMS-11 cells. When tumors reached ~100 mm³, Dovitinib 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 Xenograft Protocol (Literature [2]): Male nude mice (7 weeks old) were subcutaneously implanted with 4×10⁶ HepG2 cells. When tumors reached ~120 mm³, Dovitinib (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 recorded every 3 days [2]
\n- Phase I Clinical Protocol (Literature [4]): Eligible patients with advanced solid tumors (ECOG PS 0–2) received oral Dovitinib once daily in 28-day cycles. Dose escalation started at 50 mg/day, with subsequent doses of 100 mg, 200 mg, 300 mg, 400 mg. Patients were monitored for adverse events (CTCAE v3.0); PK samples were collected on days 1 and 15 [4]

Rat pharmacokinetics (Reference [3]): Male Sprague-Dawley rats (8 weeks old) were orally administered dovitinib 20 mg/kg: oral bioavailability = 58%, Cmax = 4.2 μM, Tmax = 1.3 h, terminal t₁/₂ = 7.8 h. Intravenous injection of 5 mg/kg: CL=8.5 mL/min/kg, Vss=1.2 L/kg [3]
- Human pharmacokinetics (reference [4]): At the maximum tolerated dose (MTD=300 mg/day), patients' Cmax=5.5 μM, Tmax=2.0 h, t₁/₂=9.2 h; plasma protein binding rate=99% (equilibrium dialysis)[4]
- Metabolism (reference [3]): In human liver microsomes, dovitinib is mainly metabolized by CYP3A4 (70%) and CYP2D6 (20%); the amount of the original drug excreted in urine is <6% [3]

In vitro cytotoxicity: In normal human hepatocytes (NHH) and peripheral blood mononuclear cells (PBMC), the survival rate of dovitinib (at concentrations up to 10 μM, 72 hours) was >80%, indicating low nonspecific toxicity [1][2]
- Acute in vivo toxicity: Rats treated with dovitinib 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]
- Phase I clinical toxicity (reference [4]): 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 (occurring in 1/6 of 400 mg doses) and Grade 3 diarrhea (occurring in 1/6 of 400 mg doses), with the maximum tolerated dose (MTD) defined as 300 mg/day [4]

[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]. Clin Cancer Res . 2011 Jul 1;17(13):4389-99.

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 also inhibit other members of the RTK superfamily, including vascular endothelial growth factor receptor, fibroblast growth factor receptor 1, platelet-derived growth factor receptor 3, FMS-like tyrosine kinase 3, stem cell factor receptor (c-KIT), and colony-stimulating factor receptor 1; this may lead to further reductions 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 a receptor tyrosine kinase (RTK) inhibitor with potential antitumor activity. Dovitinib binds to type III-V RTKs (such as vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR)) and inhibits their phosphorylation, thereby promoting the proliferation and survival of certain cancer cells. In addition, 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
Its use has been investigated in the treatment of multiple myeloma and solid tumors.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, as well as VEGF and platelet-derived growth factor (PDGF). FGF receptor tyrosine kinase inhibitors have potential therapeutic significance for multiple myeloma patients whose cancer cells highly express FGF receptors.

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Dovitinib (TKI-258, CHIR-258) is a multi-target tyrosine kinase inhibitor targeting FGFR, VEGFR, and PDGFR 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][4]
- Its mechanism of action involves binding to the ATP-binding pocket of the target kinases, inhibiting the activation of tyrosine kinases and downstream signaling (FGFR/VEGFR/PDGFR: ERK/AKT), thereby blocking cell proliferation, inducing apoptosis, and inhibiting angiogenesis[1][3][4]
- 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 treating multiple types of cancer[1][4]

C21H21FN6O

392.43

392.176

C, 64.27; H, 5.39; F, 4.84; N, 21.42; O, 4.08

405169-16-6

Dovitinib lactate;692737-80-7;Dovitinib dilactic acid;852433-84-2;Dovitinib-d8;1246819-84-0;Dovitinib lactate hydrate;915769-50-5

135398510

Light yellow to green yellow solid powder

1.4±0.1 g/cm3

1.691

1.59

3

6

2

29

678

0

FC1=C([H])C([H])=C([H])C2=C1C([H])=C(C(N2N([H])[H])=O)C1=NC2C([H])=C([H])C(=C([H])C=2N1[H])N1C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C1([H])[H]

PIQCTGMSNWUMAF-UHFFFAOYSA-N

InChI=1S/C21H21FN6O/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/h2-6,11H,7-10H2,1H3,(H,24,25)(H3,23,26,29)

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

TKI-258; CHIR-258; TKI258; TKI-258; Dovitinib; 405169-16-6; CHIR-258; TKI-258; 4-Amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one; Dovitinib [INN]; Dovitinib (TKI-258, CHIR-258); Dovitinib lactate; TKI 258; CHIR258; CHIR-258; CHIR 258; Dovitinib lactate

2934.99.03.00

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.37 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.37 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.37 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 30% PEG400+0.5% Tween80+5% propylene glycol: 30 mg/kg

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 (Please use freshly prepared in vivo formulations for optimal results.)