chemistry

Panobinostat

Panobinostat 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 Panobinostat rather than just read about it. In short: Panobinostat, sold under the brand name Farydak, is a medication used for the treatment of multiple myeloma. It is a hydroxamic acid and acts as a non-selective histone deacetylase inhibitor (pan-HDAC inhibitor).

Key takeaways

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

Reference excerpt

Panobinostat, sold under the brand name Farydak, is a medication used for the treatment of multiple myeloma. It is a hydroxamic acid and acts as a non-selective histone deacetylase inhibitor (pan-HDAC inhibitor). Panobinostat was approved for medical use in the United States in February 2015, and in the European Union in August 2015. However, in March 2022, it was withdrawn in the United States.

Medical uses Panobinostat is used in combination with the anti-cancer drug bortezomib and the corticoid dexamethasone for the treatment of multiple myeloma in adults who had received at least two previous treatments, including bortezomib and an immunomodulatory agent.

Contraindications Panobinostat is contraindicated in nursing mothers. To judge from experiments in animals, there is a risk for the unborn child if used during pregnancy; still, the benefit of panobinostat may outweigh this risk.

Side effects Common side effects (in more than 10% of patients) include low blood cell counts (pancytopenia, thrombocytopenia, anaemia, leucopenia, neutropenia, lymphopenia), airway infections, as well as unspecific reactions such as fatigue, diarrhoea, nausea, headache, and sleeping problems.

Pharmacology

Mechanism of action Panobinostat inhibits multiple histone deacetylase enzymes, a mechanism leading to apoptosis of malignant cells via multiple pathways.

Pharmacokinetics Panobinostat is absorbed quickly and almost completely from the gut, but has a significant first-pass effect, resulting in a total bioavailability of 21%. Highest blood plasma levels in patients with advanced cancer are reached after two hours. Plasma protein binding is about 90%. The substance is metabolised mainly through oxidation by the liver enzyme CYP3A4 and to a small extent by CYP2D6 and CYP2C19. It is also reduced, hydrolyzed and glucuronidized by unspecified enzymes. All metabolites seem to be inactive. Biological half-life is estimated to be 37 hours. 29–51% are excreted via the urine and 44–77% via the faeces.

Clinical trials As of August 2012, it is being tested against Hodgkin's Lymphoma, cutaneous T cell lymphoma (CTCL) and other types of malignant disease in Phase III clinical trials, against myelodysplastic syndromes, breast cancer and prostate cancer in Phase II trials, and against chronic myelomonocytic leukemia (CMML) in a Phase I trial. As of 2014 panobinostat is being used in a Phase I/II clinical trial that aims at curing AIDS in patients on highly active antiretroviral therapy (HAART). In this technique, panobinostat is used to drive the HIV DNA out of the patient's DNA, in the expectation that the patient's immune system in combination with HAART will destroy it. As of 2016 panobinostat is being studied in a phase II trial for relapsed and refractory diffuse large B-cell lymphoma (DLBCL).

Preclinical studies Panobinostat has been found to synergistically act with sirolimus to kill pancreatic cancer cells in the laboratory in a Mayo Clinic study. In the study, investigators found that this combination destroyed up to 65 percent of cultured pancreatic tumor cells. The finding is significant because the three cell lines studied were all resistant to the effects of chemotherapy – as are many pancreatic tumors. Panobinostat has also been found to significantly increase in vitro the survival of motor neuron (SMN) protein levels in cells of patients with spinal muscular atrophy. Panobinostat was able to selectively target triple negative breast cancer (TNBC) cells by inducing hyperacetylation and cell cycle arrest at the G2-M DNA damage checkpoint; partially reversing the morphological changes characteristic of breast cancer cells. Panobinostat, along with other HDAC inhibitors, is also being studied for potential to induce virus HIV-1 expression in latently infected cells and disrupt latency. These resting cells are not recognized by the immune system as harboring the virus and do not respond to antiretroviral drugs. A 2015 study suggested Panobinostat was effective in preventing diffuse intrinsic pontine glioma cell growth in vitro and in vivo, identifying it as a potential drug candidate. Panobinostat was also identified as a senolytic, effective at killing senescent cells.

References

Illustrations

Worked examples

Example 1 — a first encounter with Panobinostat

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

In research: Panobinostat 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 Panobinostat 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: Panobinostat is common in secondary-school and first-year university syllabi. It links to neighbouring topics CYP2D6 inhibitors, Cancer treatments, Drugs developed by Novartis, so understanding it makes those chapters shorter.
In everyday life: Look for Panobinostat 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 Panobinostat in 20 minutes

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

Frequently asked questions

What is Panobinostat in simple terms?

Why does Panobinostat 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 Panobinostat?

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 Panobinostat.