Sirolimus, also known as rapamycin, sold under brand names such as Rapamune, is a macrolide compound used to cover coronary stents, prevent organ transplant rejection, treat rare lung diseases called lymphangioleiomyomatosis, and treat perivascular epithelioid cell tumors (PEComa) It has an immunosuppressive function in the human body and is particularly useful in preventing renal transplantation rejection. It is a mechanistic target of rapamycin kinase (mTOR) inhibitors and inhibits their activation by reducing the sensitivity of T and B cells to interleukin-2 (IL-2)
Immunosuppressant
Rapamycin (Rapa) is a new macrolide immunosuppressant. It is a white solid crystal with a melting point of 183-185 ℃. It is lipophilic. It is dissolved in organic solvents such as methanol, ethanol, acetone, and chloroform. It is very slightly soluble in water and almost insoluble in ether. It was developed as early as the 1970s. It was initially used as an antifungal drug with low toxicity. It was found to have an immunosuppressive effect in 1977. Rapa was tried as a new drug for the treatment of organ transplantation rejection in 1989. From the effect of animal experiments and clinical application, it is a new immunosuppressant with good curative effect, low toxicity, and no nephrotoxicity. Now it is often used as a drug to maintain the immune capacity of transplanted organs (especially kidney transplantation) to slow down the immune rejection after organ transplantation. However, scientists recently found another use: it can be used to treat Alzheimer's disease (Alzheimer's disease). What interested them was that the main component of rapamycin also existed in the bacterial products in the isolated soil of resurrection island. The latest experiments showed that the substance could restore the ability to recognize defects when applied to the infected mice. Rapamycin is a macrolide antibiotic, which is similar to the structure of paroxetine (FK506) but has a very different immunosuppressive mechanism. FK506 inhibits the proliferation of T lymphocytes from the G0 phase to the G1 phase, while Rapa blocks signal transduction through different cytokine receptors and blocks the process of T lymphocytes and other cells from the G1 phase to the S phase. Compared with FK506, Rapa can block calcium-dependent and calcium-independent signal transduction pathways of T lymphocytes and B lymphocytes. Medical researchers at the University of Chicago used commercially available rapamycin oral tablets and grapefruit juice to treat melanoma, a common malignant tumor disease in Europe and America, which can greatly improve the anticancer effect of other chemotherapy drugs and prolong the survival time of patients. Studies have shown that rapamycin is easily decomposed by enzymes after entering the digestive tract, and grapefruit juice contain a large number of furanocoumarins, which can inhibit the destructive effect of digestive tract enzymes on rapamycin, so it can improve the bioavailability of rapamycin. It is said that the earliest Dutch doctors have found that grapefruit juice can improve the oral absorption effect of Shaming. Now doctors in European and American countries apply it to rapamycin preparation.
Targeted drugs for cancer therapy
Recent studies have found that rapamycin target protein (mTOR) is an intracellular kinase, and the abnormality of its conduction pathway can induce a variety of diseases. Rapamycin, as a targeted inhibitor of mTOR, can be used to treat tumors closely related to this pathway, including renal cell carcinoma, lymphoma, lung cancer, liver cancer, breast cancer, neuroendocrine carcinoma, and gastric cancer. Especially for the treatment of two rare diseases, Lam and TSC (tuberous sclerosis), Lam and TSC can also be considered neoplastic diseases to some extent.
Coronary stent coating
The antiproliferative effect of sirolimus has also been combined with coronary stents to prevent coronary restenosis after balloon angioplasty. Sirolimus is formulated with a polymer coating to provide controlled release during healing after coronary intervention. Several large clinical studies have shown that patients treated with sirolimus-eluting stents have a lower rate of restenosis compared with bare-metal stents, thereby reducing repeat surgery. A sirolimus-eluting coronary stent is sold under the trade name cipher by Cordis of Johnson & Johnson. [9] However, such stents may also increase the risk of vascular thrombosis.
Vascular malformation
Sirolimus is used to treat vascular malformations. Sirolimus treatment can reduce pain and the fullness of vascular malformations, improve blood coagulation levels and slow down the growth of abnormal lymphatic vessels. sirolimus is a relatively new drug for the treatment of vascular malformations in recent years, sirolimus has become a new medical option for vascular tumors and vascular malformations. As a mammalian target of rapamycin (mTOR), sirolimus can integrate signals from PI3K / Akt pathway to coordinate appropriate cell growth and proliferation. Therefore, sirolimus is an ideal choice for proliferative vascular tumors by controlling the tissue overgrowth disorder caused by an improper activation of the PI3K / Akt / mTOR pathway as an antiproliferative agent.