chemistry

Lenvatinib

Lenvatinib is a chemistry 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 Lenvatinib rather than just read about it. In short: Lenvatinib, sold under the brand name Lenvima among others, is an anti-cancer medication for the treatment of certain kinds of thyroid cancer and for other cancers as well. It was developed by Eisai Co. and acts as a multiple kinase inhibitor against the VEGFR1, VEGFR2 and VEGFR3 kinases.

Key takeaways

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

Reference excerpt

Lenvatinib, sold under the brand name Lenvima among others, is an anti-cancer medication for the treatment of certain kinds of thyroid cancer and for other cancers as well. It was developed by Eisai Co. and acts as a multiple kinase inhibitor against the VEGFR1, VEGFR2 and VEGFR3 kinases.

Medical uses Lenvatinib is approved (since 2015) for the treatment of differentiated thyroid cancer that is either locally recurrent or metastatic, progressive, and did not respond to treatment with radioactive iodine (radioiodine). In May 2016, the US Food and Drug Administration (FDA) approved it (in combination with everolimus) for the treatment of advanced renal cell carcinoma following one prior anti-angiogenic therapy. The drug is also approved in the US and in the European Union for hepatocellular carcinoma that cannot be removed surgically in patients who have not received cancer therapy by mouth or injection.

Adverse effects Hypertension (high blood pressure) was the most common side effect in studies (73% of patients, versus 16% in the placebo group), followed by diarrhoea (67% vs. 17%) and fatigue (67% vs. 35%). Other common side effects included decreased appetite, hypotension (low blood pressure), thrombocytopenia (low blood platelet count), nausea, muscle and bone pain.

Interactions As lenvatinib moderately prolongs QT time, addition of other drugs with this property could increase the risk of a type of abnormal heart rhythm, namely torsades de pointes. No relevant interactions with enzyme inhibitors and inducers are expected.

Pharmacology

Mechanism of action Lenvatinib is a multi-targeted receptor tyrosine kinase inhibitor that blocks several key proteins involved in cancer-related signalling pathways. It inhibits the three main vascular endothelial growth factor receptors (VEGFR1, VEGFR2, and VEGFR3), as well as fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3, and FGFR4), platelet-derived growth factor receptor (PDGFR) alpha, c-Kit, and the RET proto-oncogene. Inhibition of VEGFR2 is considered the primary cause of the most common side effect, hypertension. Lenvatinib exhibits strong inhibitory activity against VEGFR1, 2, and 3 RTKs, with Ki values of 1.3, 0.74, and 0.71 nM, respectively. It also inhibits FGFR1, 2, and 3 RTKs (Ki = 22, 8.2, and 15 nM, respectively), as well as RET and KIT (Ki = 1.5 and 11 nM, respectively).

Pharmacokinetics Lenvatinib is absorbed quickly from the gut, reaching peak blood plasma concentrations after one to four hours (three to seven hours if taken with food). Bioavailability is estimated to be about 85%. The substance is almost completely (98–99%) bound to plasma proteins, mainly albumin.

Lenvatinib is metabolized by the liver enzyme CYP3A4 to desmethyl-lenvatinib (M2). M2 and lenvatinib itself are oxidized by aldehyde oxidase (AO) to substances called M2' and M3', the main metabolites in the feces. Another metabolite, also mediated by a CYP enzyme, is the N-oxide M3. Non-enzymatic metabolization also occurs, resulting in a low potential for interactions with enzyme inhibitors and inducers. Terminal half-life is 28 hours, with about two thirds being excreted via the feces, and one quarter via the urine.

Chemistry Lenvatinib is used in form of the mesylate salt (CAS number 857890-39-2 ).

History A phase I clinical trial in cancer patients was performed in 2006. A phase III trial treating thyroid cancer patients started in March 2011. Lenvatinib was granted orphan drug status for treatment of various types of thyroid cancer that do not respond to radioiodine in the US and Japan in 2012 and in Europe in 2013. In February 2015, the U.S. FDA approved lenvatinib for treatment of progressive, radioiodine refractory differentiated thyroid cancer. In May 2015, European Medicines Agency (EMA) approved the drug for the same indication. In May 2016, the FDA approved it (in combination with everolimus) for the treatment of advanced renal cell carcinoma following one prior anti-angiogenic therapy. In August 2018, the FDA approved lenvatinib for the first-line treatment of people with unresectable hepatocellular carcinoma (HCC).

References

Illustrations

Worked examples

Example 1 — a first encounter with Lenvatinib

Start with the simplest possible case. Write down what Lenvatinib claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, 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 Lenvatinib 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 Lenvatinib 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 Lenvatinib

In research: Lenvatinib appears in chemistry 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 Lenvatinib 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: Lenvatinib is common in secondary-school and first-year university syllabi. It links to neighbouring topics Carboxamides, Chloroarenes, Cyclopropyl compounds, so understanding it makes those chapters shorter.
In everyday life: Look for Lenvatinib 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 Lenvatinib in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Lenvatinib 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 Lenvatinib out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Lenvatinib in simple terms?

Why does Lenvatinib matter?

Because it connects several chemistry 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 Lenvatinib?

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 Lenvatinib.