chemistry

Relugolix

Relugolix 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 Relugolix rather than just read about it. In short: Relugolix, sold under the brand names Orgovyx and Relumina among others, is a gonadotropin-releasing hormone antagonist (GnRH receptor antagonist) medication which is used in the treatment of prostate cancer, uterine fibroids and endometriosis. It is taken by mouth.

Key takeaways

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

Reference excerpt

Relugolix, sold under the brand names Orgovyx and Relumina among others, is a gonadotropin-releasing hormone antagonist (GnRH receptor antagonist) medication which is used in the treatment of prostate cancer, uterine fibroids and endometriosis. It is taken by mouth. Side effects of relugolix include menstrual abnormalities, hot flashes, excessive sweating, headache, and decreased bone mineral density. Relugolix is a GnRH antagonist, or an antagonist of the gonadotropin-releasing hormone receptor. Unlike most other GnRH modulators, but similarly to elagolix (brand name Orilissa), relugolix is a non-peptide, small-molecule compound and is orally active. It suppresses sex hormone levels to the postmenopausal or castrate range in both women and men.

Medical uses Relugolix is approved in the United States, Canada and the United Kingdom for the treatment of prostate cancer, in Japan for the treatment of uterine fibroids (uterine leiomyoma) and in the United Kingdom for endometriosis.

Available forms Relugolix is available in the form of 40 and 120 mg oral tablets.

Side effects The main side effects of relugolix for uterine fibroids include abnormal uterine bleeding (24.6–48.6% vs. 6.3% for placebo), hot flashes (42.8–45.5% vs. 0% for placebo), heavy menstrual bleeding (12.1–49.3% vs. 9.4% for placebo), headache (12.3–15.2%), and excessive sweating (9.4–15.2% vs. 0% for placebo). In addition, decreased bone mineral density occurs with relugolix (21.7% decrease by week 12, 24.4% decrease by week 24).

Pharmacology

Pharmacodynamics

Relugolix is a selective antagonist of the gonadotropin-releasing hormone receptor (GnRHR), with a half-maximal inhibitory concentration (IC50) of 0.12 nM. A dosage of relugolix of 40 mg once per day has been found to suppress estradiol levels to postmenopausal levels (<20 pg/mL) within 24 hours in premenopausal women. In the control group of women, estradiol levels fluctuated between 50 and 250 pg/mL. Estradiol levels have been found to return to normal concentrations within 4 weeks of discontinuation of relugolix in premenopausal women. The medication additionally suppresses levels of progesterone, luteinizing hormone, and follicle-stimulating hormone in premenopausal women. Relugolix at a dosage of 40 mg or more once per day has been found to reduce testosterone levels to sustained castrate levels (<20 ng/dL) in men. It additionally suppresses luteinizing hormone and follicle-stimulating hormone levels in men. Lower doses of relugolix (<40 mg/day) are under investigation for achieving partial sex hormone suppression in the treatment of endometriosis and uterine fibroids. This is intended to reduce the incidence and severity of menopausal symptoms such as hot flushes and decreased bone mineral density that are secondary to estrogen deficiency.

Pharmacokinetics A single 40-mg oral dose of relugolix has been found to result in peak levels of relugolix of 29 ng/mL (47 nmol/L) after 1.5 hours. Steady-state levels are reached within 7 days with 40 mg/day relugolix administration. There is an approximate 2-fold accumulation of relugolix by 2 weeks of continuous administration. Food diminishes the oral bioavailability of relugolix by about 50%. Relugolix is a substrate for P-glycoprotein, which may have a limiting effect on its absorption and distribution. The plasma protein binding of relugolix is approximately 68 to 71% over a concentration range of 0.05 to 5 μg/mL. Relugolix is not a substrate for CYP3A4. The elimination half-life of relugolix is 36 to 65 hours across a dosage range of 20 to 180 mg/day. There is moderate to high interindividual variability in systemic exposure to relugolix. Relugolix is excreted mainly in feces (83%) and to a small degree in urine (4%). Only about 6% of a dose of relugolix is excreted unchanged.

Chemistry Relugolix is a non-peptide, small-molecule compound, and is structurally distinct from GnRH analogues. It is an N-phenyl urea derivative.

Synthesis The discovery route of relugolix was recently reported: A scalable process was also developed recently:

A Gewald aminothiophene synthesis between 4-nitrophenylacetone [5332-96-7] (1) and ethyl cyanoacetate [105-56-6] (2) in the presence of sulfur and triethylamine to give an aminothiophene [174072-89-0]. The amino group was protected with cathyl chloride to give the corresponding carbamate, [308831-93-8] (3). Alkylation with 2,6-Difluorobenzyl chloride [697-73-4] (4) gave [308831-94-9]. Next, a free-radical bromination gave [308831-95-0] (5). Displacement of the bromide with (2-methoxyethyl)(methyl)amine [38256-93-8] (6) and subsequent catalytic hydrogenation of the nitro group gave PC53388810 (7). The aniline was reacted with CDI, and the resulting imidazolide was further treated with methoxyamine [67-62-9] to give the urea [737789-92-3] (8). A cyclization reaction mediated by diethyl pyrocarbonate (DEPC) in the presence of 3-methoxy-6-aminopyridazine [7252-84-8] (9) followed by exposure to sodium methoxide generated thymine derivative [737789-61-6] (10). Quaternization of the basic amine with 1-chloroethyl chloroformate followed by displacement with dimethylamine completed the synthesis of relugolix (11).

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Relugolix

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

In research: Relugolix 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 Relugolix 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: Relugolix is common in secondary-school and first-year university syllabi. It links to neighbouring topics 2,6-Difluorophenyl compounds, Dimethylamino compounds, Ethers, so understanding it makes those chapters shorter.
In everyday life: Look for Relugolix 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 Relugolix in 20 minutes

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

Frequently asked questions

What is Relugolix in simple terms?

Why does Relugolix 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 Relugolix?

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 Relugolix.