| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
PLK2 0.31 μM (IC50) PLK1 >10 μM (IC50) PLK3 >10 μM (IC50) PLK4 >10 μM (IC50)
ON1231320 specifically targets Polo-like kinase 2 (PLK2). It is a highly selective inhibitor with an IC50 of 0.31 uM for PLK2. It demonstrates excellent selectivity, showing no significant inhibitory effect against other members of the PLK family, including PLK1, PLK3, and PLK4 (all with IC50 values greater than 10 uM). The compound is an ATP-competitive inhibitor, meaning it binds to the ATP-binding pocket of the kinase. |
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| ln Vitro |
With IC50 values greater than 10 μM, ON1231320 (compound 7ao) exhibits no inhibitory effect against PLK1, PLK3, or PLK4 [1]. In human tumor cells, ON1231320 (0–5 μM; 24 hours) triggers programmed cell death [1]. 16 tumor cell lines (IC50=0.035-0.2 μM) are inhibited by ON1231320 (DU145, MCF-7, BT474, SK-OV-3, MIA-PaCa-2, SK-MEL-28, A549, U87, COLO -205, HELA, H1975, RAJI, U205, K562, GRANTA-519)[1]. Tubulin polymerization is not substantially inhibited by ON1231320 [1]. Human fibroblasts that are normal are unaffected by ON1231320 [2].
In vitro, ON1231320 potently inhibits the proliferation of a broad panel of 16 human tumor cell lines, with IC50 values ranging from 0.035 to 0.2 uM. Mechanistically, it blocks tumor cell cycle progression specifically in the G2/M phase of mitosis, leading to the induction of apoptotic cell death. At concentrations up to 5 uM, the compound effectively triggers programmed cell death in a time-dependent manner in human tumor cells. |
| ln Vivo |
ON1231320 (compound 7ao; 75 mg/kg; intraperitoneal injection; given every other day, or Q2D) for 20 days. tumour development was markedly suppressed[1].
In vivo efficacy has been demonstrated. The compound has shown good in vivo anticancer activity in a MOLM-13 xenograft model (as noted for the related compound BAY-1143572 in some references), suggesting that it can suppress tumor growth. While provided summaries do not detail a specific xenograft study for ON1231320, its ability to block the cell cycle in vitro strongly supports its potential for in vivo tumor growth inhibition and future cancer research applications. |
| Enzyme Assay |
A cell-free luminescent kinase assay (e.g., ADP-Glo assay) is used to determine the IC50 of ON1231320 against PLK2. Purified recombinant PLK2 enzyme, a peptide substrate, and ATP are incubated in a reaction buffer. The compound is added to the reaction mixture. After the reaction, an ADP detection reagent is added to convert the ADP produced into luminescence. The luminescent signal is measured, and the IC50 is calculated based on the reduction in kinase activity compared to a control.
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| Cell Assay |
Apoptosis Analysis[1]
Cell Types: U2OS cells Tested Concentrations: 0-5 µM Incubation Duration: 24 hrs (hours) Experimental Results: Increased the activity of Caspases 3/7 in a dose-dependent manner. Induced apoptosis. For cellular studies, tumor cell lines such as HeLa, DU145, MCF-7, or A549 are seeded in 96-well plates and allowed to adhere overnight. Cells are then treated with serial dilutions of ON1231320 (e.g., 0 to 5 uM) for 24 to 72 hours. Cell viability is measured using a standard assay like MTT or CellTiter-Glo. Cell cycle distribution is analyzed by flow cytometry after propidium iodide (PI) staining to confirm G2/M phase arrest. Apoptosis is confirmed by Annexin V/PI staining. |
| Animal Protocol |
Animal/Disease Models: 6-8 week old NCR nu/nu female mice with MDAMB-231 triple negative breast cancer cells[1]
Doses: 75 mg/kg Route of Administration: IP; alternate days (Q2D) for 20 days Experimental Results: Resulted in significant inhibition of tumor growth (86.5%) A typical in vivo efficacy study involves using immunocompromised mice (e.g., NOD-SCID) bearing subcutaneous xenografts of a human tumor cell line sensitive to PLK2 inhibition. When tumors reach a defined volume (e.g., 100-200 mm3), mice are randomized and treated with ON1231320. The compound is dissolved in a suitable vehicle (e.g., 10% DMSO + 90% (20% SBE-beta-CD in Saline)) and administered by intraperitoneal (IP) injection, possibly daily. Tumor volume is measured with calipers two to three times per week. |
| ADME/Pharmacokinetics |
Specific ADME (Absorption, Distribution, Metabolism, and Excretion) data for ON1231320 is not detailed in the provided literature. The compound is soluble in DMSO at 50 mg/mL, which allows for the preparation of stock solutions for both in vitro and in vivo dosing. For in vivo studies, it is formulated as a suspension (2.5 mg/mL) in a vehicle such as 10% DMSO + 90% (20% SBE-beta-CD in Saline) for intraperitoneal (IP) injection, indicating it is suitable for in vivo pharmacology studies.
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| Toxicity/Toxicokinetics |
Preclinical toxicology data for ON1231320 is not provided in the summaries. As a highly specific PLK2 inhibitor, its on-target toxicities are predicted to be related to its inhibition of PLK2 function. However, the specific toxicities observed in animal models are not described. The endpoints in efficacy studies, such as weight loss and tumor size, are typically used as initial indicators of general tolerability. It is a research compound only.
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| References | |
| Additional Infomation |
ON1231320 is a highly specific chemical probe for studying the biological function of Polo-like kinase 2 (PLK2). PLK2 is a serine/threonine-protein kinase involved in cell cycle regulation, particularly the G1/S and G2/M checkpoints. The compound is a valuable tool for dissecting the role of PLK2 in cancer and for validating it as a potential drug target. It is currently in the preclinical research stage and has not been approved for human use. It is also sometimes referred to as GBO-006.
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| Molecular Formula |
C22H15F2N5O3S
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|---|---|
| Molecular Weight |
467.448009729385
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| Exact Mass |
467.086
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| CAS # |
1312471-39-8
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| PubChem CID |
67240318
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| Appearance |
Light yellow to green yellow solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
33
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| Complexity |
897
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C=CC(=CC=1F)F)(C1=CC2=CN=C(NC3C=CC4=C(C=CN4)C=3)N=C2N(C)C1=O)(=O)=O
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| InChi Key |
ZEHBZHZMQSHZFI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H15F2N5O3S/c1-29-20-13(9-19(21(29)30)33(31,32)18-5-2-14(23)10-16(18)24)11-26-22(28-20)27-15-3-4-17-12(8-15)6-7-25-17/h2-11,25H,1H3,(H,26,27,28)
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| Chemical Name |
6-(2,4-difluorophenyl)sulfonyl-2-(1H-indol-5-ylamino)-8-methylpyrido[2,3-d]pyrimidin-7-one
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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 (106.96 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.35 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 sonication.
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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1393 mL | 10.6963 mL | 21.3927 mL | |
| 5 mM | 0.4279 mL | 2.1393 mL | 4.2785 mL | |
| 10 mM | 0.2139 mL | 1.0696 mL | 2.1393 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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