science

Wortmannin

Wortmannin is a science topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Wortmannin rather than just read about it. In short: Wortmannin, a steroid metabolite of the fungi Penicillium funiculosum, Talaromyces wortmannii, is a non-specific, covalent inhibitor of phosphoinositide 3-kinases (PI3Ks). It has an in vitro inhibitory concentration (IC50) of around 5 nM, making it a more potent inhibitor than LY294002, another commonly used PI3K inhibitor.

Key takeaways

Wortmannin belongs to science; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Wortmannin to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Wortmannin from memory before moving on to harder problems.

Reference excerpt

Wortmannin, a steroid metabolite of the fungi Penicillium funiculosum, Talaromyces wortmannii, is a non-specific, covalent inhibitor of phosphoinositide 3-kinases (PI3Ks). It has an in vitro inhibitory concentration (IC50) of around 5 nM, making it a more potent inhibitor than LY294002, another commonly used PI3K inhibitor. It 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-PKcs, some phosphatidylinositol 4-kinases, myosin light chain kinase (MLCK) and mitogen-activated protein kinase (MAPK) at high concentrations Wortmannin has also been reported to inhibit members of the polo-like kinase family with IC50 in the same range as for PI3K. The half-life of wortmannin in tissue culture is about 10 minutes due to the presence of the highly reactive C20 carbon that is also responsible for its ability to covalently inactivate PI3K. Wortmannin is a commonly used cell biology reagent that has been used previously in research to inhibit DNA repair, receptor-mediated endocytosis and cell proliferation.

Phosphoinositide-3-kinase Phosphoinositide-3-kinase (PI3K) activates an important cell survival signaling pathway, and constitutive activation is seen in ovarian, head and neck, urinary tract, cervical and small cell lung cancer. PI3K signaling is attenuated by the phosphatase activity of the tumor suppressor PTEN that is absent in a number of human cancers. Inhibiting PI3K presents the opportunity to inhibit a major cancer cell survival signaling pathway and to overcome the action of an important deleted tumor suppressor, providing antitumor activity and increased tumor sensitivity to a wide variety of drugs. Wortmannin is a PI3K inhibitor; as such, it has detrimental influence on memory and impairs spatial learning abilities.

Derivatives Medicinal chemistry research has been conducted to identify wortmannin derivatives that are more stable, while not losing its therapeutic effect.

Sonolisib

One of these, sonolisib (PX-866), has been shown to be an irreversible inhibitor of PI-3 kinase with efficacy when delivered orally. Sonolisib was put in a phase 1 clinical trial by Oncothyreon. The clinical development plan for sonolisib includes both standalone and combination therapy in major human cancers. In 2010, sonolisib was starting 4 phase II trials for solid tumors. The company gave an update on its phase 2 trials in Jun 2012. Phase 1 results (with docetaxel) published Aug 2013. In July 2014 published results of a phase 2 trial (for NSCLC) concluded : "The addition of PX-866 to docetaxel did not improve PFS, response rate, or OS in patients with advanced, refractory NSCLC without molecular preselection". In Sept 2015 as Phase 2 trial for recurrent glioblastoma reported not meeting its primary endpoint.

References

External links Media related to Wortmannin at Wikimedia Commons

Wortmannin bound to proteins in the PDB

Illustrations

Worked examples

Example 1 — a first encounter with Wortmannin

Start with the simplest possible case. Write down what Wortmannin claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In science, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Wortmannin before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Wortmannin ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Wortmannin

In research: Wortmannin appears in science research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Wortmannin in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Wortmannin is common in secondary-school and first-year university syllabi. It links to neighbouring topics Acetate esters, Covalent inhibitors, Delta-lactones, so understanding it makes those chapters shorter.
In everyday life: Look for Wortmannin outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Wortmannin in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Wortmannin means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Wortmannin out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Wortmannin in simple terms?

Why does Wortmannin matter?

Because it connects several science ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Wortmannin?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Wortmannin.