chemistry

Nelfinavir

Nelfinavir 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 Nelfinavir rather than just read about it. In short: Nelfinavir, sold under the brand name Viracept, is an antiretroviral medication used in the treatment of HIV/AIDS. Nelfinavir belongs to the class of drugs known as protease inhibitors (PIs) and, like other PIs, it is almost always used in combination with other antiretroviral drugs.

Key takeaways

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

Reference excerpt

Nelfinavir, sold under the brand name Viracept, is an antiretroviral medication used in the treatment of HIV/AIDS. Nelfinavir belongs to the class of drugs known as protease inhibitors (PIs) and, like other PIs, it is almost always used in combination with other antiretroviral drugs. Nelfinavir is an orally bioavailable human immunodeficiency virus HIV-1 protease inhibitor (Ki = 2 nM) and is widely prescribed in combination with HIV reverse transcriptase inhibitors for the treatment of HIV infection. It was patented in 1992 and approved for medical use in 1997.

Toxicity Common (>1%) adverse effects include insulin resistance, hyperglycemia, and lipodystrophy. Nelfinavir can produce a range of adverse effects. Flatulence, diarrhea, or abdominal pain are common (i.e. experienced by more than one in a hundred patients). Fatigue, urination, rash, mouth ulcers, or hepatitis are less frequent effects (experienced by one in a thousand to one in a hundred patients). Nephrolithiasis, arthralgia, leukopenia, pancreatitis, or allergic reactions may occur, but are rare (less than one in a thousand patients) .

Other bioactivity

Antiviral Nelfinavir inhibits the maturation and export of the herpes simplex 1 virus and the Kaposi's sarcoma virus.

Anti-virulence activity Nelfinavir and simple derivatives inhibit the production of the virulence factor streptolysin S, a cytolysin produced by the human pathogen Streptococcus pyogenes. Nelfinavir and its derivatives did not exhibit detectable antibiotic activity, but did inhibit the production of other biologically active molecules, including plantazolicin (antibiotic), listeriolysin S (cytolysin), and clostridiolysin S (cytolysin), by other bacteria.

Interactions

Nelfinavir's interaction profile is similar to that of other protease inhibitors. Most interactions occur at the level of the cytochrome P450 isozymes CYP3A4 and CYP2C19, by which nelfinavir is metabolized. For example, nelfinavir reportedly inhibited the metabolism of atorvastatin and simvastatin.

Pharmacology

Nelfinavir should be taken with food. Taking the drug with food reduces the risk of diarrhea as an adverse effect.

Mechanism of action Nelfinavir is a protease inhibitor: it inhibits HIV-1 and HIV-2 proteases. HIV protease is an aspartate protease, which splits viral protein molecules into smaller fragments and is vital to both replication of the virus within the cell and also to release of mature viral particles from an infected cell. Nelfinavir is a competitive inhibitor (2 nM), which is designed to bind tightly and is not cleaved because of the presence of a hydroxyl group, as opposed to a keto group, in the middle amino acid residue mimic, which would be otherwise S-phenylcysteine. All protease inhibitors bind to the protease, and the precise mode of binding determines how the molecule inhibits the protease. The way in which nelfinavir binds the enzyme may be sufficiently unique to reduce cross-resistance between it and other PIs. Also, not all PIs inhibit both HIV-1 and HIV-2 proteases.

History Nelfinavir was developed by Agouron Pharmaceuticals as part of a joint venture with Eli Lilly and Company. Agouron Pharmaceuticals was acquired by Warner Lambert in 1999 and is now a subsidiary of Pfizer. Nelfinavir is marketed in Europe by Hoffman-La Roche and elsewhere by ViiV Healthcare. The US Food and Drug Administration (FDA) approved nelfinavir for therapeutic use in March 1997, making it the twelfth approved antiretroviral. The initial product launched proved to be the largest "biotech launch" in the history of pharmaceutical companies, achieving first full year sales exceeding $US335M. Agouron's patent on the drug expired in 2014. In June 2007, both the Medicines and Healthcare products Regulatory Agency and the European Medicines Agency put out an alert requesting the recall of any nelfinavir in circulation, because some batches may have been contaminated with potentially cancer-causing chemicals.

Research Since 2009, nelfinavir has been under investigation for potential use as an anti-cancer agent. When applied to cancer cells in culture (in vitro), it can inhibit the growth of a variety of cancer types and can trigger cell death (apoptosis). When nelfinavir was given to laboratory mice with tumours of the prostate or of the brain, it suppressed tumour growth. At the cellular level, nelfinavir exerts multiple effects to inhibit cancer growth; the two main ones appear to be inhibition of the Akt/PKB signaling pathway and activation of endoplasmic reticulum stress with subsequent unfolded protein response. In the USA, about three dozen clinical trials are being conducted (or have been completed) in order to determine whether nelfinavir is effective as a cancer therapeutic agent in humans. In some of these trials, nelfinavir has been used alone in monotherapy, whereas in others it has been combined with other modes of cancer therapy, such as well-established chemotherapeutic agents or radiation therapy. As of April 2022, nelfinavir is being studied as a radiosensitizing agent as part of treatment of advanced cervical cancer.

References

Illustrations

Worked examples

Example 1 — a first encounter with Nelfinavir

Start with the simplest possible case. Write down what Nelfinavir 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 Nelfinavir 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 Nelfinavir 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 Nelfinavir

In research: Nelfinavir 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 Nelfinavir 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: Nelfinavir is common in secondary-school and first-year university syllabi. It links to neighbouring topics Benzamides, CYP3A4 inhibitors, Decahydroisoquinolines, so understanding it makes those chapters shorter.
In everyday life: Look for Nelfinavir 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 Nelfinavir in 20 minutes

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

Frequently asked questions

What is Nelfinavir in simple terms?

Why does Nelfinavir 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 Nelfinavir?

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 Nelfinavir.