Wortmannin (KY 12420)

Biological Activity

Wortmannin (SL-2052) is a potent and specific PI3K inhibitor. The 50% inhibitory concentration for inhibition by wortmannin is 2 to 4 nM. Wortmannin inhibits polo-like kinase 1 (PLK1) with IC50 of 5.8 nM. Wortmannin displays a similar potency in vitro for the class I, II, and III PI3K members although it can also inhibit other PI3K-related enzymes such as mTOR, DNA-PK, some phosphatidylinositol 4-kinases, myosin light chain kinase (MLCK) and mitogen-activated protein kinase (MAPK) at high concentrations.

Product Citations

• 

  Platelets. 2023 Feb 22;2173505.

  Alantolactone induces platelet apoptosis by activating the Akt pathway
  Wortmannin (KY 12420) purchased from AbMole

• 

  Front Pharmacol. 2021 Sep 23;12:749930.

  Carbamazepine Induces Platelet Apoptosis and Thrombocytopenia Through Protein Kinase A
  Wortmannin (KY 12420) purchased from AbMole

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  J Infect Dis. 2018 May 8.

  Tumor Necrosis Factor-α Is Required for Mast Cell-Mediated Host Immunity Against Cutaneous Staphylococcus aureus Infection.
  Wortmannin (KY 12420) purchased from AbMole

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  J Agric Food Chem. 2017 Mar 15;65(10):2089-2099.

  10-Gingerol, a Phytochemical Derivative from “Tongling White Ginger”, Inhibits Cervical Cancer: Insights into the Molecular Mechanism and Inhibitory Targets
  Wortmannin (KY 12420) purchased from AbMole

Customer Product Validations & Biological Datas

	Source	J Infect Dis (2018). Figure 7. Wortmannin (Abmole Bioscience)
	Method	Western blotting
	Cell Lines	mast cells
	Concentrations	10 μM
	Incubation Time	30 minutes
	Results	The S. aureus-induced production of TNF-α and CRAMP was significantly reduced by pretreatment with the specific PI3K inhibitor Wortmannin or the specific NF-κB inhibitor PDTC

	Source	APMIS.m (2017). Figure 7. wortmannin (Abmole Bioscience Inc. Houston, TX, USA)
	Method	Western blot
	Cell Lines	HeLa cells
	Concentrations
	Incubation Time
	Results	Moreover, cell pretreatment with wortmannin could reduce the expression level of p-PI3K, followed by slight augmentation in the inhibitory effects of 10-G on HeLa cells.

Protocol (for reference only)

Cell Experiment
Cell lines	Human pancreatic adenocarcinoma cell lines PK1 and PK8
Preparation method	Drug Treatments. For flow cytometric analysis, cells were treated with the drug vehicle (≤1% DMSO) or 20 μM gemcitabine (2′,2′-diflurodeoxycytidine; Eli Lily & Co., Indianapolis, IN) for 48 h or with the same concentration of gemcitabine for the same duration followed by wortmannin (50–400 nM) or LY294002 (15–120 μM) for 4 h in the continuous presence of gemcitabine. The concentration and duration of gemcitabine treatment were chosen based on preliminary studies examining its effects on cell cycle inhibition and induction of apoptosis. For Western blotting, cells were treated with similar concentrations of wortmannin or LY294002 alone for 4 h or with gemcitabine (20 and 40μ M) alone for 48 h before harvest. Wortmannin and LY294002 were purchased from Biomol (Philadelphia, PA). All compounds were dissolved in DMSO at a stock concentration of 10 mM, stored at −20°C, and added to cell cultures at a final concentration of ≤1% DMSO, with appropriate solvent additions to control cultures. All experiments were performed in triplicate.
Concentrations	50–400 nM
Incubation time	48 h

Animal Experiment
Animal models	mice bearing Orthotopic Model
Formulation	dissolved at 0.4 mg/ml in DMSO, and diluted with 0.9% NaCl before use.
Dosages	single bolus injections of 0.7 mg/kg
Administration	via the tail vein

Chemical Information

Molecular Weight	428.43
Formula	C23H24O8
CAS Number	19545-26-7
Solubility (25°C)	DMSO ≥ 60 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Wymann MP, et al. Mol Cell Biol. Wortmannin inactivates phosphoinositide 3-kinase by covalent modification of Lys-802, a residue involved in the phosphate transfer reaction.

[2] Powis G, et al. Cancer Res. Wortmannin, a potent and selective inhibitor of phosphatidylinositol-3-kinase.