Talk:Sirolimus

History of the drug

I came here to fact-check the entertaining Radiolab Episode on this drug (Qari S, Walters P, Lechtenberg S (21 May 2021). "The Dirty Drug and the Ice Cream Tub | Radiolab". WNYC Studios. Retrieved 25 July 2021. Given in Source number 8) Unfortunately, the article states nothing about the interesting history... Should a section about this be added or is this normally not done in biomedical articles? 147.161.165.93 (talk) 08:59, 13 August 2021 (UTC)

Hi! History sections are very welcome. The problem in this case is that Wikipedia should only include material based on reliable sources. I don't know much about Radiolab, but a podcast normally doesn't count as reliable. See WP:Reliable sources for more. If you by any chance know a better source for the drug's history, feel free to include it, or ask for help here. (I'm watching this page and will notice any requests on this talk page.) Best regards --ἀνυπόδητος (talk)

Name? Sirolimus vs Rapamycin

Should the drug really be listed as its trade name, rather than the common chemical one? btavshanjian

I agree, all other drug articles i've seen on WP are under their chemical name, not their trade name, especially since the trade name can differ across countries. --81.205.3.113 (talk) 00:39, 15 July 2009 (UTC)

Looking at popularity, "Rapamycin" produces 11372 records on PubMed, "Sirolimus" gives 8178. I think it also makes sense to have the title of the article be "rapamycin" since the intro paragraph gives the origin of the term "rapa". I don't know how the INN/USAN factor weighes into this arguement. --Tea with toast (talk) 01:36, 29 October 2009 (UTC)

Per WP:MEDMOS, INNs should always be used as article titles. I am a major supporter of this guideline, which is in keeping with the original purpose of INNs—providing a completely unambiguous, internationally recognizable names with no industry or trade connotations. Fvasconcellos (t·c) 03:21, 29 October 2009 (UTC)

If there is complete consensus on this, is the trade name used only because some company PR people are dominating the site? — Preceding unsigned comment added by 75.61.141.90 (talk) 01:28, 20 August 2012 (UTC)

In the section on "Autism in Mice" the cited research paper does not mention "Sirolimus" at all, only "Rapamycin" so in the interest of accuracy I changed the names to agree with the citation. — Preceding unsigned comment added by 75.61.141.90 (talk) 01:37, 20 August 2012 (UTC)

Maybe Fvasconcellos didn't make himself entirely clear: "Sirolimus" is not the trade name but the International Nonproprietary Name (INN). Rapamycin is an old name that is still often seen, but we should stick with our guidelines (WP:MOSMED#Drugs, medications and devices) and use the INN, "sirolimus". Also, I think it is confusing to use different names for the same substance, depending on how the respective sources call it -- therefore I'll undo your last edit, although I'm aware you had good intentions. Please tell me (preferably here) if you disagree. Cheers, ἀνυπόδητος (talk) 10:52, 20 August 2012 (UTC)

Autism section

Is retardism really the best terminology to be used here? —Preceding unsigned comment added by 90.152.14.118 (talk) 09:16, 25 September 2008 (UTC)

I don't think so personally. Standard IQ tests that are used to diagnose and define retardation unfortunately rely heavily on verbal skills. If there is anyone out there that knows of a testing method that defines congnitive ability independantly of verbal skill, I would like to hear of it. It is unfair to those affected by ASD to not separate the two. How to do that may be another question!Melanie.brown35 (talk) 22:19, 29 January 2009 (UTC)

Structure?

Is the stereochemistry of the structure correct? I'm finding differences in online structures as to what the stereochemistry to the methyl group near the lactone should be. (Hashed bond in upper left) (Also posted on image talk page)-- 16:07, 31 January 2007 (UTC)

I created the image using Image:Sirolimus1.gif as a model, then checked it for accuracy against CID 6436030 from PubChem. If the stereochemistry is inaccurate, I apologize; I'll try to find alternate sources and re-check. Fvasconcellos 22:51, 31 January 2007 (UTC)

Apparently it was incorrect. Fixed now, as is the IUPAC name—the one previously in the article was actually for tacrolimus. Thank you. Fvasconcellos 01:25, 1 February 2007 (UTC)

Gimrudghk (talk) 01:25, 27 July 2008 (UTC)Silorimus have several side effects. For example anemia, edema etc.

Sirolimus/ Late Thrombosis

Inclusion of the statement of the rapamycin DES stent (known as Cypher and sometimes denoted as SES) may be misleading since the exact reason is debatable. One postulate includes what Dr. Renu Virmani at Armed Forces Reseach Laboratories calls a polymer hypersensitivity. If this is correct, then the statement should be included on a Wikipedia page on the Cypher stent and not on the rapamycin/sirolimus page. CClaude 216.140.123.24 (talk) 20:00, 2 December 2008 (UTC)

More precise longevity statement

"A 2009 study indicated that rapamycin can prolong the life of mice. If this increase in lifespan were translated to human years, it might allow humans to live more than a hundred years". That could use a rewrite. Something like, "If these results were replicable in humans, average lifespan could be extended to over 100 years." 206.223.190.7 (talk) 22:46, 9 July 2009 (UTC)

• Looks like this was corrected some time ago. I agree results in mice cannot be so extrapolated to humans, that hypothetical IF was doing a lot of work there. Phil (talk) 15:46, 19 April 2022 (UTC)

Cost - use of grapefruit

A comment regarding the use of grapefruit to lower doses and costs of the drug have been frequently added or removed over the past few months. I have deleted the comment.

Grapefruit (and many other foods) is an inhibitor of CYP450 and will affect the metabolism of many drugs. The CYP450 wiki entry gives more detail.

Grapefruit should not be consumed with Siromilus. Bombauer (talk) 17:11, 5 April 2010 (UTC)Bombauer

Patents

The referenced US patent 5,665,7220 does not exist, in fact it has one too many digits to be a valid patent number. The earliest US patent referencing rapamycin is 3,929,992 filed in 1974, although 5,675,732 claims a more efficient means of production and would only recently have expired. 199.246.40.54 (talk) 13:46, 6 August 2010 (UTC)

Also 5,212,155 expires in Nov 2010 and 5,100,899 expires Jan 7, 2014 (both re inhibiting transplant rejection) [1] Rod57 (talk) 11:38, 8 October 2010 (UTC)

Removed report of in-vitro work

Removed from cancer section as not notable (re sirolimus) since only in-vitro :

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 studies were all resistant to the effects of chemotherapy-as are many pancreatic tumors.

Rod57 (talk) 11:59, 8 October 2010 (UTC)

Wyeth is now Pfizer

Shouldn't Wyeth be changed to Pfizer? It should be considering Wyeth's drug portfolio is now owned by Pfizer! — Preceding unsigned comment added by 82.195.117.137 (talk) 10:59, 10 February 2012 (UTC)

Anti proliferative

Has anyone investigated using Sirolimus for psoriasis? — Preceding unsigned comment added by 71.9.22.214 (talk) 19:49, 2 April 2015 (UTC)

Serolimus (rapamycin) in Sleep regulation

At least one studie is using rapamycin as the drug name when reporting its use in sleep and circadian rhythm research in a PLoS Biology paper.

Athanasios Metaxakis, Luke S. Tain, Sebastian Grönke, Oliver Hendrich, Yvonne Hinze, Ulrike Birras, Linda Partridge. Lowered Insulin Signalling Ameliorates Age-Related Sleep Fragmentation in Drosophila. PLoS Biology, 2014; 12 (4): e1001824 DOI: 10.1371/journal.pbio.1001824

Redwolfe (talk) 13:01, 10 July 2015 (UTC)

References

Alzheimer's Disease

"Because sirolimus is already approved for other indications, it should be easy to start a clinical trial to see whether it works in humans." One or more doctors treating Alzheimer's patients may have already prescribed sirolimus, observed that it had no effect at all, and never published the negative results.Schmausschmaus (talk)

Orphaned references in Sirolimus

I check pages listed in Category:Pages with incorrect ref formatting to try to fix reference errors. One of the things I do is look for content for orphaned references in wikilinked articles. I have found content for some of Sirolimus's orphans, the problem is that I found more than one version. I can't determine which (if any) is correct for this article, so I am asking for a sentient editor to look it over and copy the correct ref content into this article.

Reference named "pmid22168436":

• From David M. Sabatini: Magnuson B, Ekim B, Fingar DC (January 2012). "Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks". Biochem. J. 441 (1): 1–21. doi:10.1042/BJ20110892. PMID 22168436.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• From Mechanistic target of rapamycin: Magnuson B, Ekim B, Fingar DC (January 2012). "Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks". Biochem. J. 441 (1): 1–21. doi:10.1042/BJ20110892. PMID 22168436.

I apologize if any of the above are effectively identical; I am just a simple computer program, so I can't determine whether minor differences are significant or not. AnomieBOT⚡ 12:17, 4 March 2016 (UTC)

IL-2 production or signal inhibited??

Currently the first paragraph ends with: "It inhibits activation of T cells and B cells by reducing the production of interleukin-2 (IL-2)." I am confused, as later it is said to inhibit the signal transduction of the IL-2 receptor. I'm changing this sentence to reflect the information I found on https://compendium.ch/mpro/mnr/21159/html/de#7550 (unfortunately not an english source). If someone could verify this and add an english citation, that would of course be great! --134.21.47.157 (talk) 16:11, 12 January 2017 (UTC)

• Rapamycin acts exclusively by inhibiting mTOR. In the case of lymphocytes, this causes their arrest at the G1/S checkpoint and prevents IL-2 synthesis. Such immunosuppressive effects have been described in detail for the past 20 years, see e.g. http://www.jbc.org/content/270/16/9454.abstract and http://www.sciencedirect.com/science/article/pii/0024320595022333 Cheers. Neodop (talk) 18:54, 12 January 2017 (UTC)

Siroliums for FAVA

Should there be a section about using Sirolimus to treat/manage fibroadipose vascular anomalies? https://www.deepdyve.com/lp/wiley/fibroadipose-vascular-anomaly-treated-with-sirolimus-successful-6nFSNoG0P4 http://www.childrenshospital.org/conditions-and-treatments/conditions/f/fibro-adipose-vascular-anomaly/diagnosis-and-treatment Samsmachado (talk) 18:41, 19 January 2020 (UTC)

Biosynthesis

The biosynthesis section tells the same story three times in a row in different wordings. It should be condensed into a single, more comprehensive narrative. 85.196.224.45 (talk) 21:14, 17 December 2020 (UTC)

Effects on longevity

One of the sources in the longevity section points to a PR release about the failure of this linked trial of an entirely different drug Dactolisib. It seems like that reference should be removed and information about that trial perhaps moved to that page. [2] The statement "The known adverse effects caused by sirolimus and marketed analogs at the doses used in transplant regimens, especially the increased risk of infection due to immunosuppression, as well as dose-dependent metabolic impairment, make it unlikely that chronic, long-term treatment with sirolimus could become a widely used anti-aging agent" does not seem supported at all by the other linked source after it, which is actually fairly positive about the potential at non-transplant dosages noting " Our findings suggest that a therapeutic window for rapamycin may exist in which the beneficial effects of rapamycin of aging and age-related diseases mediated by mTORC1 inhibition can be realized while minimizing mTORC2-related side effects" referencing evidence related to intermittent dosing very different from transplant dosage regimes. The sentence in the article seems for no sourced reason based on "at the doses used in transplant regimes" which is NOT what is being suggested or tested in early stage trials such as this one [3]. Placing this here for any discussion before proceeding with any edits, primarily the removal of the unrelated source & the updating of the sentence to something more accurately reflecting the still pre-human trial if potentially positive information about benefits of non-transplant dosage regimes. Phil (talk) 15:40, 19 April 2022 (UTC)

I came here to note this. A major 2013 source notes both the potential benefits and the drawbacks, and points out that dosing and timing of rapamycin administration for preventative/longevity purposes remain to be determined. It takes a positive tone in describing the potential of rapamycin as a longevity drug. I would support changing the sentence to more neutrally note the potential and the issues. Casting doubt on the potential of the drug seems like editorializing.

"Current estimates suggest cognitive decline can be detected as early as 45 years of age in otherwise healthy people72. Loss of cognitive function is a leading concern among geriatricians and their elderly patients and is a significant and growing public-health burden. If mTORC1 inhibition has even a modest positive effect on cognitive function, it could improve the quality of life for millions of middle-aged and older adults. Add to this the likelihood that risks of developing some forms of cancer, cardiovascular disease, and neurodegenerative disease would be reduced, then mTOR inhibitors may offer an attractive opportunity to have a significant impact on preventive health care.

Before this can happen, however, important questions must be answered. Rapamycin is not without side effects, including hyperlipidaemia and hyperglycaemia, anaemia and stomatitis, in patients. A recent study of long-term rapamycin treatment in mice reported increased incidence of cataracts and testicular degeneration40. The effects of mTORC1 inhibition on immune function and wound healing are also of particular concern. Although it is unclear whether rapamycin alone has substantial immunosuppressive effects in healthy individuals, it undoubtedly is immunomodulatory. It would be unfortunate to take a drug that slows the rate of ageing, only to succumb to infection from an otherwise innocuous bacterium or virus at an early age. Optimal dosage and duration of treatment are also unknown factors. Almost no information exists on the most effective dose of rapamycin for longevity or healthspan in mice, and the current data suggest that rapamycin therapy that begins late in life is nearly as effective as therapy that begins early in life, at least for longevity. Understanding whether this is also true for a variety of age-related pathologies will be important. Assessing risks and side effects from studies of patients with disorders such as the rare lung disease lymphangioleiomyomatosis, for which rapamycin is indicated for chronic use, may be informative in determining the clinical potential of this drug and other mTOR inhibitors in the setting of age-related disease." 35.0.192.16 (talk) 22:32, 16 October 2022 (UTC)

The absence of pushback since April and the support of the sources here make me feel justified in altering the sentence to a less negative/more neutral take on rapamycin's potential as a longevity drug. If others disagree, feel free to pursue further debate here. AllAmericanBreakfast (talk) 22:34, 16 October 2022 (UTC)

Dr Surendra Sehgal

It is amazing that the main guy who isolated the compound is never mentioned. I added his name, hoping to add an article on him later. Somebody removed it. Oh, well. Life is like that. — Preceding unsigned comment added by Toofani tarzan (talk • contribs) 21:33, 25 May 2022 (UTC)

Hi! I don't know why your addition was removed, but one common reason is lacking a good source for the statement. So if you know a reliable source saying that Sehgal isolated sirolimus, be welcome to add this piece of information. Please contact me if you need any help. --ἀνυπόδητος (talk) 07:04, 26 May 2022 (UTC)

LOY-001 cant prolong the life of dog

they will do the test of another drug LOY-002 Name8864 (talk) 04:43, 1 December 2023 (UTC)

Removal of "society and culture" section

I removed this section because it did not discuss any relevant information, and only contained information about a newly approved non-generic product of the same substance. This section was out of place, and essentially read like a press release from the company or an interested party. Just-a-can-of-beans (talk) 17:40, 31 December 2023 (UTC)