Sirolimus (Rapamycin)

• CAS: 53123-88-9
• Catalog Number: ACM53123889-2
• Category: Others
• Molecular Weight: 914.17
• Molecular Formula: C51H79NO13
• Description: Sirolimus, also known as rapamycin, is a natural macrocyclic lactone produced by the bacterium Streptomyces hygroscopicus, with immunosuppressant properties. In cells, sirolimus binds to the immunophilin FK Binding Protein-12 (FKBP-12) to generate an immunosuppressive complex that binds to and inhibits the activation of the mammalian Target Of Rapamycin (mTOR), a key regulatory kinase. This results in inhibition of T lymphocyte activation and proliferation that occurs in response to antigenic and cytokine (IL-2, IL-4, and IL-15) stimulation and inhibition of antibody production.
• Synonyms: RAPA; RAP; RPM; SLM; AY 22989; AY22989; AY-22989; SILA 9268A; WY090217; WY-090217; WY 090217; C07909; D00753; sirolimus; rapamycin; Rapamune
• IUPAC Name: (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34, 34a-hexadecahydro-9,27-dihydroxy-3-[(1R)-2-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido[2,1-c][1,4] oxaazacyclohentriacontine-1,5,11,28,29 (4H,6H,31H)-pentone
• Canonical SMILES: C[C@@H](C([C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(C[C@@H]([C@H](C)C[C@@H]1CC[C@@H](O)C(OC)C1)OC2=O)=O)=O)C[C@H](C)/C=C/C=C/C=C(C)/[C@@H](OC)C[C@H]3O[C@](C(C(N4[C@H]2CCCC4)=O)=O)(O)[C@H](C)CC3
• InChI: InChI=1S/C51H79NO13/c1-30-16-12-11-13-17-31(2)42(61-8)28-38-21-19-36(7)51(60,65-38)48(57)49(58)52-23-15-14-18-39(52)50(59)64-43(33(4)26-37-20-22-40(53)44(27-37)62-9)29-41(54)32(3)25-35(6)46(56)47(63-10)45(55)34(5)24-30/h11-13,16-17,25,30,32-34,36-40,42-44,46-47,53,56,60H,14-15,18-24,26-29H2,1-10H3/b13-11+,16-12+,31-17+,35-25+/t30-,32-,33-,34-,36-,37+,38+,39+,40-,42+,43+,44?,46-,47+,51-/m1/s1
• InChI Key: QFJCIRLUMZQUOT-PYYJPVDBSA-N
• Solubility: Soluble in DMSO, not in water
• Appearance: White to off-white solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: Rapamycin (Sirolimus; AY 22989) is a potent and specific mTOR inhibitor with an IC50 of 0.1 nM in HEK293 cells.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 67.01; H, 8.71; N, 1.53; O, 22.75
• Exact Mass: 913.55514
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: To further investigate the role of autophagy in the regulation of PTSC senescence and the potential mechanisms involved, this study examined the protein expression levels of autophagy markers and SASP markers with bleomycin and rapamycin treatments. First, the expression of p62, which was inversely correlated with autophagy, was increased in the bleomycin-treated PTSCs (Figure 3(a)). The addition of rapamycin reversed the p62 expression to the basal level as in the control group (Figures 3(a) and 3(b)). Meanwhile, as an indicator of autophagy activation, the LC3 II/LC3 I expression ratio was significantly reduced by bleomycin treatment in the PTSCs, but rapamycin antagonized this decrease (Figures 3(a) and 3(c)). Moreover, rapamycin at the dose of 25 nM completely inhibited the downstream responder S6 phosphorylation, indicating an inhibition of the mTOR signaling pathway (Figure 3(a)).; Reference: Stem Cells Int. 2021; 2021: 6638249. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870298/
• In Vivo Activity: As expected, rapamycin treatment effectively prevented the AA-induced increase in mTOR and S6K1 phosphorylation, which led to marked elevations in AA-induced renal expression of the autophagy markers (Fig. 2). This suggested that inhibiting mTOR activity by rapamycin further activated renal autophagy. Autophagy and apoptosis are two connected pathological processes involved in the development of AAN. To determine the effects of rapamycin on renal apoptosis in AAN mice, the protein expression of Bcl-2 and Bax, common markers of apoptosis, was assessed in kidney tissues using western blotting. The results indicated that the kidney tissue of AA-treated mice presented with decreased expression of Bcl-2 and increased expression of Bax, which were reversed by rapamycin treatment (Fig. 2A, G and H), suggesting that rapamycin inhibited apoptosis in the kidneys of AA-treated renal injury mice. Taken together, these observations indicate that rapamycin supplementation inhibits the renal activity of mTOR, which promotes renal autophagy, thereby probably suppressing the apoptosis of kidney tissues in mice with AA-induced renal injury.; Reference: Mol Med Rep. 2021 Jul; 24(1): 495. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127069/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).