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| Targets |
ZINC05007751 targets NIMA-related kinase NEK6, a serine/threonine kinase involved in cell cycle regulation, particularly in mitotic progression and spindle assembly. NEK6 has been implicated in cancer cell proliferation and survival. By inhibiting NEK6, ZINC05007751 disrupts cell cycle progression and induces antiproliferative effects. The compound shows high selectivity for NEK1 and NEK6, with minimal activity against NEK2, NEK7, and NEK9, indicating a favorable selectivity profile.
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| ln Vitro |
ZINC05007751 (6 μM-190 μM; 24 hours) has an IC50 below 100 μM and suppresses the development of MDA-MB-231, PEO1, NCI-H1299, and HCT-15 [1]. The PEO1 cell cycle is perturbed by ZINC05007751 [1]. With cisplatin, ZINC05007751 (ovarian cancer cell PEO1) exhibits a synergistic impact that reduces the cisplatin IC50 from 7.9 µM to 0.1 µM. The greatest synergistic effect is demonstrated by the combination of ZINC05007751 (44 µM) + cisplatin (10 µM) [1].
In vitro, ZINC05007751 shows antiproliferative activity against a panel of human cancer cell lines. It displays a synergistic effect with cisplatin and paclitaxel in BRCA2-mutated ovarian cancer cell lines. The IC50 for NEK6 inhibition is 3.4 ± 1.2 µM as determined in LANCE-Ultra kinase assays. The structurally related analog ZINC04384801 showed slightly higher potency with an IC50 of 2.6 ± 0.05 µM. The compound's antiproliferative activity is likely mediated through NEK6 inhibition and subsequent disruption of mitotic progression. |
| ln Vivo |
In vivo, ZINC05007751 has not been extensively characterized in published literature. Based on its in vitro antiproliferative activity and synergistic effects with standard chemotherapeutics, it has potential for in vivo efficacy studies in cancer models. The compound's selectivity for NEK6 and its ability to synergize with cisplatin and paclitaxel suggest that it could enhance the efficacy of these drugs in vivo. However, specific in vivo efficacy data have not been detailed in the available literature.
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| Enzyme Assay |
For in vitro kinase assays, recombinant NEK6 protein is incubated with a peptide substrate and ATP in kinase assay buffer. The LANCE-Ultra kinase assay is commonly used, where kinase activity is measured by detecting the phosphorylation of a ULight-labeled peptide substrate using a terbium-labeled anti-phospho antibody. The test compound is added at various concentrations (typically 0.01-100 µM). Time-resolved fluorescence resonance energy transfer (TR-FRET) signal is measured, and IC50 values are calculated by fitting dose-response curves.
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| Cell Assay |
Cytotoxicity assay[1]
Cell Types: MDA-MB-231, PEO1, NCI-H1299 and HCT-15 Cell Tested Concentrations: 6 μM-190 μM Incubation Duration: 24 hrs (hours) Experimental Results: Inhibition of the growth of MDA-MB-231, PEO1, NCI-H1299 and HCT-15. For cell proliferation assays, human cancer cell lines (including BRCA2-mutated ovarian cancer cells) are seeded in 96-well plates and treated with ZINC05007751 at concentrations ranging from 0.1-100 µM, alone or in combination with cisplatin or paclitaxel. Cells are incubated for 48-72 hours, and cell viability is assessed using MTT, CCK-8, or CellTiter-Glo assays. Synergy is evaluated using the Chou-Talalay combination index method. IC50 values are calculated from dose-response curves to determine antiproliferative potency. |
| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice would be implanted with BRCA2-mutated ovarian cancer cells. When tumors reach a predetermined size, mice would be randomized to receive ZINC05007751 alone, cisplatin or paclitaxel alone, or combination treatments. Tumor volumes would be measured twice weekly. At study endpoint, tumors would be collected for histological analysis and biomarker evaluation to assess NEK6 inhibition and antiproliferative effects. However, specific in vivo protocols have not been reported in the available literature.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of ZINC05007751 have not been fully characterized. The compound is soluble in DMSO (61 mg/mL, 200.46 mM) but insoluble in water and ethanol. For in vivo administration, it can be formulated as a homogeneous suspension in CMC-Na (≥5 mg/mL) or as a clear solution in 5% DMSO + 30% PEG300 + 65% H2O or 5% DMSO in corn oil. Storage is recommended at -20°C. Further PK studies including half-life, bioavailability, and tissue distribution would be required.
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| Toxicity/Toxicokinetics |
Toxicological data for ZINC05007751 have not been reported in the available literature. As a research compound, it is intended for laboratory use only and is not for human or veterinary use. Standard safety precautions should be followed when handling this compound. Comprehensive toxicology studies have not been performed, and the compound's safety profile in vivo has not been established.
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| References | |
| Additional Infomation |
ZINC05007751 is a potent and selective inhibitor of NIMA-related kinase NEK6 with an IC50 of 3.4 µM. It shows antiproliferative activity against human cancer cell lines and synergistic effects with cisplatin and paclitaxel in BRCA2-mutated ovarian cancer cells. The compound is highly selective for NEK1 and NEK6 with no significant activity against NEK2, NEK7, or NEK9. It is a research tool for studying NEK6 biology and is not approved for clinical use.
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| Molecular Formula |
C18H12N2O3
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| Molecular Weight |
304.29948425293
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| Exact Mass |
304.084
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| Elemental Analysis |
C, 71.05; H, 3.97; N, 9.21; O, 15.77
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| CAS # |
591239-68-8
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| Related CAS # |
591239-68-8;
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| PubChem CID |
2275754
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| Appearance |
Brown to black solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
504.9±50.0 °C at 760 mmHg
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| Flash Point |
259.2±30.1 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.646
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| LogP |
3.44
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
23
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| Complexity |
632
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1C(=CC=C1/C=C1\C(NC(C(C#N)=C\1C)=O)=O)C1C=CC=CC=1
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| InChi Key |
SNLNUUWCOAPJED-ZROIWOOFSA-N
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| InChi Code |
InChI=1S/C18H12N2O3/c1-11-14(17(21)20-18(22)15(11)10-19)9-13-7-8-16(23-13)12-5-3-2-4-6-12/h2-9H,1H3,(H,20,21,22)/b14-9-
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| Chemical Name |
(5Z)-4-methyl-2,6-dioxo-5-[(5-phenylfuran-2-yl)methylidene]pyridine-3-carbonitrile
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| Synonyms |
ZINC05007751; ZINC-05007751; ZINC 05007751
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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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). This product is not stable in solution, please use freshly prepared working solution for optimal results. |
| 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 : ~8.33 mg/mL (~27.37 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2862 mL | 16.4312 mL | 32.8623 mL | |
| 5 mM | 0.6572 mL | 3.2862 mL | 6.5725 mL | |
| 10 mM | 0.3286 mL | 1.6431 mL | 3.2862 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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