Shaanxi BLOOM Tech Co., Ltd. is one of the most experienced manufacturers and suppliers of rapamycin powder cas 53123-88-9 in China. Welcome to wholesale bulk high quality rapamycin powder cas 53123-88-9 for sale here from our factory. Good service and reasonable price are available.
Rapamycin powder, also known as sirolimus, is a yellow solid crystal with the chemical formula of C51H79NO13, lipophilic, soluble in organic solvents such as methanol, ethanol, acetone, chloroform ether, dimethylformamide, very slightly soluble in water, n-hexane petroleum ether, almost insoluble in ether, is a new and efficient immunosuppressant. it is a white to milky white crystalline solid, usually in the form of needle shaped crystals or crystalline powders. It is insoluble in water at room temperature, slightly soluble in alcohols and chloroform, and soluble in dichloromethane and dimethyl sulfoxide. Its solubility is greatly influenced by solvents and temperature. Relatively stable under light and heating conditions, but sensitive to acids and alkalis. Under acidic conditions, Rapamycin will gradually decompose, so it is necessary to avoid contact with strongly acidic substances.
In addition, Rapamycin has a low solubility in water, so it should be kept dry during storage. The molecular structure consists of a large inner ring and a smaller outer ring. Its inner ring is composed of four fused macrocycles, forming a structure similar to macrolides. Meanwhile, the outer ring of Rapamycin is composed of multiple oxygen heterocycles and side chains. This molecular structure determines the biological activity and interaction mode of Rapamycin. The particle size and specific surface area have important effects on its solubility, stability, and drug delivery. By controlling the crystal growth conditions and solvent selection during the crystallization process, the size and morphology of Rapamycin particles can be adjusted. It is a natural product widely used in the fields of medicine and chemistry. It has been found to have a range of biological activities and can be used for treating cancer, transplant rejection, autoimmune diseases, and more.
|
Chemical Formula |
C51H79NO13 |
|
Exact Mass |
914 |
|
Molecular Weight |
914 |
|
m/z |
914 (100.0%), 915 (55.2%), 916 (14.9%), 916 (2.7%), 917 (1.8%), 917 (1.5%) |
|
Elemental Analysis |
C, 67.01; H, 8.71; N, 1.53; O, 22.75 |
|
|
|
Rapamycin powder (trade name Sirolimus) is a macrocyclic lactone compound extracted from soil bacteria Streptomyces. Since its discovery, its unique mTOR (mammalian target protein of rapamycin) signaling pathway inhibition has shown wide application value in the fields of medicine, scientific research, and anti-aging.
1. Anti rejection therapy after organ transplantation
It is an important immunosuppressant in the field of organ transplantation, especially suitable for surgeries such as kidney transplantation and liver transplantation
Mechanism of action: By binding to the immune affinity protein FKBP12, a complex is formed to inhibit the activity of mTOR. MTOR is a key regulatory factor for intracellular protein synthesis, cell proliferation, and survival. Inhibiting its activity can reduce the proliferation of T cells and B cells, and decrease the immune response induced by cytokines such as IL-2 and IL-4.
Clinical advantages: Compared with traditional immunosuppressants such as cyclosporine, it does not rely on the calcium regulated phosphatase pathway, can reduce renal toxicity, and has a better inhibitory effect on chronic rejection reactions. For example, in kidney transplant patients, the combination of rapamycin and low-dose calcineurin inhibitors can reduce the incidence of acute rejection by 30% and increase the one-year survival rate of transplanted organs to over 90%.
2. Anti tumor therapy
And its derivatives (such as everolimus) show potential in various tumor treatments by inhibiting the mTOR signaling pathway:
Solid tumor treatment: effective for solid tumors such as renal cell carcinoma, breast cancer and lung cancer. For example, in patients with metastatic renal cell carcinoma, the combination of everolimus and exemestane can prolong progression free survival to 6.9 months, a 40% increase compared to monotherapy.
Hematological malignancies: In mantle cell lymphoma, apoptosis of tumor cells can be induced, with an objective remission rate of 40%.
Combination therapy strategy: When used in combination with anti angiogenic drugs (such as bevacizumab), it can simultaneously inhibit tumor cell proliferation and angiogenesis. In non-small cell lung cancer, the overall survival of the combination therapy group is extended by 3.2 months compared to the monotherapy group.
Mechanism analysis: precise regulation of mTOR signaling pathway
1. The core position of mTOR signaling pathway
Rapamycin powder is a core molecule for intracellular nutrient perception and metabolic regulation, integrating growth factors, amino acids, and energy signals to regulate processes such as protein synthesis, lipid metabolism, and autophagy. Its abnormal activation is closely related to tumors, metabolic diseases, and aging.
2. The inhibitory effect of rapamycin on mTOR
Direct inhibition: After binding to FKBP12, it specifically inhibits mTORC1 (mTOR complex 1), blocking the activation of its downstream targets S6K1 and 4E-BP1, thereby inhibiting protein synthesis and cell cycle progression.
Indirect regulation: By inducing autophagy, damaged organelles and protein aggregates within the cell are cleared, maintaining cellular homeostasis. For example, in Alzheimer's disease models, the expression of autophagy marker LC3-II can be increased and β - amyloid deposition can be reduced.
3. The multi-level role of immune regulation
T cell inhibition: It can inhibit the activation, proliferation, and cytokine secretion of T cells, reducing the attack of effector T cells on transplanted organs.
B-cell regulation: By inhibiting the differentiation of B cells into plasma cells and reducing antibody production, it alleviates humoral immune mediated rejection reactions.
Dendritic cell effects: can induce dendritic cell tolerance, promote the generation of regulatory T cells (Tregs), and further suppress immune responses.
Frontier exploration: from anti-aging to neuroprotection
1. Breakthrough in anti-aging research
Rapamycin is the first drug proven to prolong the lifespan of model organisms:
Model organism research: In mice, rapamycin can prolong the lifespan of female mice by 14% and male mice by 9%. The mechanism may be related to reducing oxidative stress, inhibiting inflammatory response, and promoting autophagy.
Human application potential: A clinical trial targeting the elderly showed that intermittent use of rapamycin (6mg twice a week) can improve immune function, reduce the incidence of infections, and no serious side effects were observed.
2. Treatment of neurodegenerative diseases
Rapamycin shows potential in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease:
Alzheimer's disease: Inhibiting the mTOR signaling pathway can reduce tau protein hyperphosphorylation and improve cognitive function. In a transgenic mouse model, after continuous administration for 6 months, spatial memory ability improved by 30%.
Parkinson's disease: can protect dopaminergic neurons and reduce alpha synuclein aggregation. In the cell model, processing can increase the survival rate of neurons by 40%.
3. Intervention for metabolic diseases
It can regulate metabolic syndrome and diabetes:
Insulin sensitivity: In mouse models, rapamycin can improve insulin resistance and lower fasting blood glucose levels. The mechanism may be related to the inhibition of mTORC2 (mTOR complex 2), but it should be noted that long-term use may inhibit mTORC2 and lead to elevated blood sugar levels.
Fat metabolism: It can reduce the accumulation of white adipose tissue, increase the activity of brown fat, and thus improve obesity related metabolic disorders.
1. Protection against cardiovascular diseases
Rapamycin powder coated stents are an important advancement in cardiovascular intervention therapy:
Prevention of in stent restenosis: Rapamycin can inhibit the proliferation of vascular smooth muscle cells and reduce the incidence of in stent restenosis. Clinical studies have shown that rapamycin coated stents reduce the restenosis rate from 20% to below 5%.
Atherosclerosis intervention: by inhibiting mTOR signaling pathway, it can reduce the formation of foam cells and delay the progression of atherosclerosis.
2. Antiviral and anti infective
Has inhibitory effects on various viruses:
Activation of HIV latent pool: can induce the replication of HIV virus from latent state, providing tools for the "shock and kill" strategy.
Cytomegalovirus prevention: In organ transplant patients, it can reduce the incidence of cytomegalovirus infection and is more effective than using ganciclovir alone.
3. Personalized medicine and combination therapy
Biomarker guidance: By detecting the activity of the mTOR signaling pathway (such as pS6K1 levels), a population of patients sensitive to rapamycin can be screened to improve treatment accuracy.
Combination immunotherapy: When used in combination with PD-1/PD-L1 inhibitors, it can enhance T cell activity. In melanoma, the objective remission rate of the combination therapy group is 20% higher than that of the monotherapy group.
We are the supplier of Rapamycin Powder.
Remark: BLOOM TECH(Since 2008), ACHIEVE CHEM-TECH is the subsidiary of us.
The US patent publication specification us20100029933a1 discloses the purification technology scheme of rapamycin. The purity of the purified product from the fermentation broth is 98.8%, the total impurity content is less than 1.2%, and the single impurity is less than 0.15%. The purification scheme is as follows:
Rapamycin in the fermentation broth was extracted with a hydrophobic solvent and concentrated;
Adding hydrophilic solvent to separate impurities;
The product obtained in the step is adsorbed on an inert carrier, continuously washed with alkali and acid, and then eluted;
Collect the eluent obtained in step C or directly use the solution containing rapamycin in step B, put it on a silica gel column, and collect the eluent;
Crystallizing the product obtained in step d);
Dissolve the crystalline product in step f and perform hydrophobic action or reverse phase chromatography; And G was recrystallized to obtain rapamycin with high purity, but the purification yield was not high. In a specific example, it can be seen that the final pure product of 11kg rapamycin fermentation broth was only 6G, and 3G pure product was further purified and crystallized to obtain 2.5G.
Synthesis of rapamycin : The core of rapamycin biosynthesis is completed by polyketide synthase type 1 ( PKS ) combined with non-ribosomal peptide synthetase ( NRPS ). The enzyme domain of rapamycin linear polyketide biosynthesis consists of three enzymes, including RapA, RapB and RapC, which contain 14 modules. Among the three enzymes, RapA completed the first four polyketide synthesis chain extensions, the last six in RapB, and the last four in RapC. Then, linear polyketide synthesis was modified by NRPS ( RapP ), and L-hexahydropyridine carboxylic acid was added at the polyketide synthesis terminal. Finally, the molecular cyclization generates the precursor product, prerapamycin.
The core macrocycle of pre-rapamycin will eventually form rapamycin through the modification of five enzymes. Firstly, the core macrocycle was modified by RapI, adenosine methionine-dependent oxygen methylase ( MTase ), and C39 was methoxylated. Second, by RapJ, cytochrome P450 modification, C9 plus carbonyl. Third, another methylase, RapM methoxy C16. Fourthly, another P-450, RapN, is hydroxylated at C27, followed by different methylases, RapQ methoxylates C27 to form rapamycin.
Rapamycin powder (also known as "sirolimus") is a secondary metabolite secreted by soil streptomyces, which was first discovered by scientists from the soil of Easter Island, Chile in 1975. Its chemical structure belongs to the "triene macrolide" compound. Rapamycin was found to have immunosuppressive effect in 1977. In 1989, Rapa was tried as a new drug to treat rejection of organ transplantation. Due to the low fermentation yield of rapamycin and the complex extraction process, the product was not developed and marketed by the American household chemicals company until 1999. At present (2010), the phase I and II clinical trials of Rapa have been completed, and the phase III clinical trials are in progress. Subsequently, it was listed in more than ten countries in Europe and America.
At that time, the indications of rapamycin approved by the US Food and Drug Administration (FDA) were not antibiotics but "immunosuppressants". This is because rapamycin has shown a strong immunosuppressive effect in clinical trials, and it can replace cyclosporine with a clinical history of more than 30 years. Moreover, compared with cyclosporine, rapamycin oral liquid has a smaller dose (only 2-3mg per time), stronger anti rejection effect and less side effects. Therefore, rapamycin has rapidly become a common oral immunosuppressant for organ transplant recipients around the world since its listing.
Rapamycin, a natural product new drug known as the late 20th century, has a history of scientific exploration and wisdom in pharmaceutical applications. Its birth not only provides new treatment methods for modern medicine, but also sets a new milestone for the research and development of natural drugs.
The story begins in 1964 when Professor Stanley Scolina from McGill University in Canada conducted a soil sample collection on Easter Island. This seemingly ordinary collection activity laid the groundwork for the development of rapamycin. Professor Skolina handed over the collected soil samples to the laboratory of Wyeth Pharmaceuticals, hoping to discover new antibiotics from them.
After years of screening and research, researchers at Wyeth Pharmaceuticals successfully isolated a substance with antifungal activity from soil samples in 1972. This substance was initially envisioned for the treatment of yeast infections, but in further cell culture experiments, researchers found that it can actually inhibit the proliferation of immune cells. This discovery has sparked a strong interest among scientists in the potential value of this substance.
In the 1980s, with the continuous progress of scientific research and technology, scientists gradually deepened their research on rapamycin. They found that rapamycin not only inhibits the proliferation of immune cells, but also has an inhibitory effect on tumor growth. This discovery has opened up a new path for the application of rapamycin in the pharmaceutical field.
In 1999, the US Food and Drug Administration (FDA) officially approved rapamycin as an immunosuppressive agent for anti rejection treatment after kidney transplantation surgery. This milestone event marks the transition of rapamycin from laboratory to clinical application, bringing good news to countless patients.
In the 21st century, with the rapid development of scientific research and technology, new breakthroughs have been made in the research of rapamycin. Scientists have discovered that two derivatives of rapamycin, tamoximus and everolimus, have shown great potential in the treatment of cancer. These two drugs were developed by Pfizer and Novartis respectively and have been successfully applied in clinical practice.
Significant progress has been made in the study of rapamycin in prolonging lifespan. In 2009, Randy Strong's laboratory at the Bashup Institute for Longevity and Aging, David E. Harrison's team at Jackson's laboratory, and Richard A. Miller's laboratory at the University of Michigan Ann Arbor jointly reported that rapamycin could extend the lifespan of mice. This discovery provides new ideas for the application of rapamycin in the field of anti-aging.
With the continuous deepening of research on the target and new pharmacological effects of rapamycin, scientists have found that it also has potential value in the treatment of other diseases. For example, researchers from Xi'an Jiaotong University have confirmed that rapamycin can improve symptoms in Graves ophthalmopathy (GO) patients by targeting CD4+CTL cells. This achievement provides a new direction for the application of rapamycin in the field of ophthalmology.
Looking back at the development history of it, we can see that it has gone through decades of scientific exploration and medical application, from a simple soil sample to becoming a treasure of modern medicine. During this process, the joint efforts of countless scientists and pharmaceutical companies have brought us this magical drug. In the future, with the continuous progress of scientific research and technology and the deepening development of the pharmaceutical field, the application prospects of rapamycin will be even broader.
Rapamycin powder is used as an immunosuppressant mainly to slow down the immune rejection after organ transplantation. However, its use is accompanied by a range of possible side effects or adverse reactions. Some of the major side effects or adverse reactions are listed below:
1. Immune system suppression
Reduced immunity: rapamycin exerts an immunosuppressive effect by inhibiting the proliferation and signaling of T lymphocytes and other cells. This may result in patients being more susceptible to infections such as bacterial, fungal, viral and other infections at an increased risk.
2. Blood system effects
Thrombocytopenia: Rapamycin may impair hematopoiesis, leading to a decrease in platelet count and an increased risk of bleeding.
Leukopenia: White blood cells are an important part of the immune system and their reduction may further weaken the patient's immunity.
Anemia: Due to impaired hematopoiesis, patients may also experience anemia.
3. Metabolic and nutritional problems
Increased serum triglycerides and cholesterol: prolonged use of rapamycin may lead to dyslipidemia and increased risk of cardiovascular disease.
4. Digestive system reactions
Nausea and vomiting: these are common digestive adverse reactions that may affect the patient's appetite and nutrient absorption.
Increased liver enzymes: indicate possible liver damage and require close monitoring of liver function.
5. Other adverse reactions
Hypertension: rapamycin may cause an increase in blood pressure, requiring regular monitoring of blood pressure and adjustment of the treatment regimen.
Drug Rash, Acne: Some patients may develop skin allergic reactions such as drug rash and acne.
Increase in other infections: patients may be more susceptible to various infections due to decreased immunity.
Hot Tags: rapamycin powder cas 53123-88-9, suppliers, manufacturers, factory, wholesale, buy, price, bulk, for sale, Cyproheptadine hydrochloride sesquihydrate, Tetracaine hydrochloride powder, daidzein powder, tofacitinib powder, Benzobarbital CAS 744 80 9, Chrysophanic Acid CAS 481 74 3