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| Targets |
VIC-1911 binds to and inhibits aurora A kinase (AURKA), a serine/threonine protein kinase essential for mitotic progression. Inhibition of AURKA disrupts the assembly of the mitotic spindle apparatus, causes abnormal chromosome segregation, and inhibits cell division, ultimately inducing apoptosis in cells overexpressing AURKA. VIC-1911 has an IC50 of 1.0-1.04 nM for AURKA and shows high selectivity over AURKB (IC50 = 95 nM, approximately 90-fold selectivity) and other protein kinases. The compound also has cross-inhibitory activity against tropomyosin receptor kinase (TRK) family members.
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| ln Vitro |
In a variety of human cancer cell lines, including paclitaxel-resistant cells, TAS-119 increases the antiproliferative effects of paclitaxel [1]. Three taxanes (paclitaxel, docetaxel, and cabazitaxel) that suppress cell proliferation in HeLa cells are dose-dependently enhanced by TAS-119 (30-300 nM). When comparing normal diploid fibroblasts to tumor cells, TAS-119 largely causes mitotic accumulation in the latter [1].
VIC-1911 potently inhibits AURKA activity with high selectivity across diverse cancer cell lines. Treatment with VIC-1911, even at nanomolar concentrations, substantially inhibits the growth of both androgen receptor-positive and androgen receptor-negative prostate cancer cells. The compound triggers mitotic failure, induces DNA double-strand breaks (DSBs), and activates the p53 pathway, halting cell division and inducing cell death. VIC-1911 disables homologous recombination-mediated repair of DSBs in otherwise HR-proficient cancer cells, leading to a "BRCAness" phenotype and pronounced accumulation of DNA damage and mitotic catastrophe. |
| ln Vivo |
TAS-119 (5-30 mg/kg; oral; twice daily on day 1 and twice daily on day 2) therapy promotes phosphorylated histone H3 (pHH3) in HeLa-luc xenograft nude mice[1] .
In vivo, VIC-1911 demonstrates synergistic effects in inhibiting xenograft tumor growth when combined with poly(ADP-ribose) polymerase (PARP) inhibitors, which have proven effective in cancers with homologous recombination deficiency. The compound sensitizes HR-proficient tumors to PARP inhibitors by inducing functional BRCAness through mitotic arrest. In prostate cancer xenograft models, combination treatment with VIC-1911 and PARP inhibitors shows enhanced antitumor efficacy compared to either agent alone. VIC-1911 has potent antitumor activity and is being evaluated as a promising therapeutic agent for advanced cancers. |
| Enzyme Assay |
Kinase inhibition assays for VIC-1911 are performed using recombinant AURKA enzyme and appropriate peptide substrates in the presence of ATP. The assay typically employs a fluorescence-based or radiometric format to measure kinase activity. VIC-1911 is incubated with the enzyme, substrate, and varying concentrations of ATP (at Km or higher concentrations). The reaction is stopped after 30-60 minutes, and product formation is quantified. IC50 values are calculated from concentration-response curves. Selectivity is assessed by screening VIC-1911 against a panel of related kinases including AURKB, AURKC, and TRK family members.
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| Cell Assay |
Cellular assays for AURKA inhibition typically employ cancer cell lines with elevated AURKA expression. Cells are treated with varying concentrations of VIC-1911 for 24-72 hours. Cell viability is assessed using MTT, CCK-8, or CellTiter-Glo assays. Apoptosis is evaluated by Annexin V/PI staining and flow cytometry. Cell cycle analysis is performed by propidium iodide staining. The induction of DNA damage is assessed by measuring γ-H2AX foci formation. The "BRCAness" phenotype is evaluated by assessing homologous recombination repair efficiency using reporter assays.
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| Animal Protocol |
Animal/Disease Models: Nude mice were injected with HeLa-luc cells [1].
Doses: 5 mg/kg, 10 mg/kg, 30 mg/kg. Route of Administration: oral administration; injection administration. twice (two times) daily on day 1 and twice (two times) daily on day 2 Experimental Results: In nude mice with HeLa-luc xenografts, all doses induced pHH3. In vivo efficacy is evaluated in murine xenograft models using human cancer cell lines. Tumor-bearing mice are treated with VIC-1911 orally at various doses (typically 10-50 mg/kg) daily or on a schedule. Tumor volumes are measured every 2-3 days. Combination studies with PARP inhibitors are conducted to assess synergistic efficacy. Pharmacodynamic markers such as phospho-AURKA, phospho-histone H3, and γ-H2AX are measured in tumor tissues to confirm target engagement. Body weight and clinical signs are monitored for tolerability assessment. |
| ADME/Pharmacokinetics |
VIC-1911 is orally bioavailable and rapidly absorbed following oral administration, with Tmax of 0.5-2 hours across animal species. The compound is rapidly eliminated regardless of administration route, with a half-life of 0.4-2.5 hours. The molecular weight is 506.36 with formula C23H22Cl2FN5O3. The compound is soluble in DMSO (50 mg/mL) and should be stored at -20°C. Pharmacokinetic properties support oral dosing in preclinical studies.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies indicate that VIC-1911 has a favorable biosafety profile. As a potent antimitotic agent targeting a kinase essential for cell division, potential toxicities may include myelosuppression, gastrointestinal effects, and other on-target toxicities associated with mitotic inhibitors. Standard safety pharmacology, genotoxicity, and repeated-dose toxicity studies would be required prior to clinical development. In preclinical studies, the compound has been evaluated in prostate cancer models with acceptable tolerability.
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| References | |
| Additional Infomation |
VIC-1911, an Aurora A kinase inhibitor, is an orally bioavailable serine/threonine protein kinase inhibitor with potential antimitotic and antitumor activities. Following intravenous injection, VIC-1911 binds to and inhibits Aurora A kinase activity, potentially leading to mitotic spindle assembly disorder, abnormal chromosome segregation, cell division inhibition, and apoptosis in cells overexpressing Aurora A kinase. Aurora A kinase is located at the spindle poles and microtubules during mitosis, playing a crucial role in the regulation of spindle assembly. Aurora A kinase is overexpressed in various cancers.
VIC-1911 is also known as TAS-119 and TAS-2104. It was developed by Taiho Pharmaceuticals and has been investigated in combination with PARP inhibitors for the treatment of prostate cancer, including both androgen receptor-positive and -negative disease. The compound's ability to induce functional BRCAness through mitotic arrest represents a novel mechanism to sensitize HR-proficient tumors to PARP inhibition. Clinical trials are being planned or conducted for advanced solid tumors. |
| Molecular Formula |
C23H22CL2FN5O3
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| Molecular Weight |
506.3569
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| Exact Mass |
505.108
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| CAS # |
1453099-83-6
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| PubChem CID |
71696703
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| Appearance |
White to off-white solid powder
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| LogP |
4.4
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
34
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| Complexity |
741
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C(=C([H])C([H])=C([H])C=1C(N1C([H])([H])C([H])([H])C(C(=O)O[H])(C([H])([H])C2C([H])=C([H])C(=C(N([H])C3C([H])=C(C([H])([H])[H])N([H])N=3)N=2)F)C([H])([H])C1([H])[H])=O)Cl
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| InChi Key |
PLAVWQHGBMTMFR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H22Cl2FN5O3/c1-13-11-18(30-29-13)28-20-17(26)6-5-14(27-20)12-23(22(33)34)7-9-31(10-8-23)21(32)15-3-2-4-16(24)19(15)25/h2-6,11H,7-10,12H2,1H3,(H,33,34)(H2,27,28,29,30)
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| Chemical Name |
1-(2,3-dichlorobenzoyl)-4-[[5-fluoro-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyridin-2-yl]methyl]piperidine-4-carboxylic acid
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| HS Tariff Code |
2934.99.9001
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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 : ~50 mg/mL (~98.74 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.11 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 20.8 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. Solubility in Formulation 2: 2.08 mg/mL (4.11 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.11 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9749 mL | 9.8744 mL | 19.7488 mL | |
| 5 mM | 0.3950 mL | 1.9749 mL | 3.9498 mL | |
| 10 mM | 0.1975 mL | 0.9874 mL | 1.9749 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.
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