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Seco Rapamycin sodium (Secorapamycin A monosodium), the sodium salt of the ring-opened product of Rapamycin, is reported not to affect the mTOR function. Rapamycin (also known as Sirolimus), a natural macrocyclic lactone isolated from the bacterium Streptomyces hygroscopicus, is a specific and potent mTOR inhibitor with IC50 of ~0.1 nM in HEK293 cells. Rapamycin was used as a kind of original antifungal antibiotic, but since it also demonstrated immunosuppressant properties, it is being used in the prevention of transplant rejection because of its immunosuppressive effect. It also exhibits activity against several transplantable tumors and slightly activity to inactive against leukemias. The immunosuppressive effect of Rapamycin is exerted by inhibiting the activation and proliferation of T cells. Rapamycin binds to FK-binding protein 12 (FKBP12) and forms the rapamycin-FKBP12 complex, which regulates an enzyme that plays an important role in the progression of the cell cycle.
Physicochemical Properties
| Molecular Formula | C₅₁H₇₈NNAO₁₃ |
| Molecular Weight | 936.15 |
| Exact Mass | 935.537 |
| Elemental Analysis | C, 64.20; H, 8.45; N, 1.47; Na, 2.41; O, 23.47 |
| CAS # | 148554-65-8 |
| Related CAS # | Seco Rapamycin;147438-27-5 |
| PubChem CID | 71772273 |
| Appearance | White to yellow solid powder |
| LogP | 5.109 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 13 |
| Rotatable Bond Count | 24 |
| Heavy Atom Count | 66 |
| Complexity | 1760 |
| Defined Atom Stereocenter Count | 14 |
| SMILES | C[C@@H]1CC[C@H](O[C@]1(C(=O)C(=O)N2CCCC[C@H]2C(=O)[O-])O)C[C@@H](/C(=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@@H]([C@@H](/C(=C/[C@@H](C)C(=O)/C=C/[C@H](C)C[C@@H]3CC[C@H]([C@@H](C3)OC)O)/C)O)OC)/C)OC.[Na+] |
| InChi Key | DNMSBJYMPJMFNS-OWGFPTNRSA-M |
| InChi Code | InChI=1S/C51H79NO13.Na/c1-31(26-35(5)45(55)47(64-10)46(56)36(6)28-34(4)41(53)23-19-32(2)27-38-21-24-42(54)44(29-38)63-9)16-12-11-13-17-33(3)43(62-8)30-39-22-20-37(7)51(61,65-39)48(57)49(58)52-25-15-14-18-40(52)50(59)60;/h11-13,16-17,19,23,28,31-32,34-35,37-40,42-44,46-47,54,56,61H,14-15,18,20-22,24-27,29-30H2,1-10H3,(H,59,60);/q;+1/p-1/b13-11+,16-12+,23-19+,33-17+,36-28+;/t31-,32+,34-,35-,37-,38+,39+,40+,42-,43+,44-,46-,47+,51-;/m1./s1 |
| Chemical Name | sodium;(2S)-1-[2-[(2R,3R,6S)-2-hydroxy-6-[(2S,3E,5E,7E,9S,11R,13R,14R,15E,17R,19E,21R)-14-hydroxy-22-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-2,13-dimethoxy-3,9,11,15,17,21-hexamethyl-12,18-dioxodocosa-3,5,7,15,19-pentaenyl]-3-methyloxan-2-yl]-2-oxoacetyl]piperidine-2-carboxylate |
| Synonyms | seco Rapamycin Sodium Salt; 148554-65-8; Secorapamycin; Seco Rapamycin (sodium salt); Seco Rapamycin Sodium; sodium;(2S)-1-[2-[(2R,3R,6S)-2-hydroxy-6-[(2S,3E,5E,7E,9S,11R,13R,14R,15E,17R,19E,21R)-14-hydroxy-22-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-2,13-dimethoxy-3,9,11,15,17,21-hexamethyl-12,18-dioxodocosa-3,5,7,15,19-pentaenyl]-3-methyloxan-2-yl]-2-oxoacetyl]piperidine-2-carboxylate; 2-Piperidinecarboxylic acid, 1-[oxo[tetrahydro-2-hydroxy-6-[14-hydroxy-22-(4-hydroxy-3-methoxycyclohexyl)-2,13-dimethoxy-3,9,11,15,17,21-hexamethyl-12,18-dioxo-3,5,7,15,19-docosapentaenyl]-3-methyl-2H-pyran-2-yl]acetyl]-, monosodium salt, [2R-[2alpha,2(S*),3alpha,6beta[2S*,3E,5E,7E,9S*,11R*,13R*,14R*,15E,17R*,19E,21R*,22(1S*,3R*,4R*)]]]- (9CI); Secorapamycin A monosodium; Secorapamycin A monosodium. |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets |
Rapamycin impurity; ring-opened product of Rapamycin. - Seco Rapamycin (Secorapamycin A) does not significantly affect mTOR function and no IC50, Ki, or EC50 values were reported in the literature [1]. |
| ln Vitro |
Seco Rapamycin Disposition in Caco-2 Cell Monolayers and Human Tissue Homogenates. In order to ascertain if Seco Rapamycin (D2) may be converted into dihydro Sirolimus (M2), human liver, jejunal mucosal, and Caco-2 homogenates are cultured with 20 μM Seco Rapamycin. In a NADPH-dependent way, M2 was generated by each of these homogenates. At a dose of 100 μM, ketoconazole does not affect the production of M2 in any of the homogenates that were tested. Caco-2 cell monolayers are treated with 20 μM Seco Rapamycin to see if it may be converted to M2 in intact cells. Little Seco Rapamycin is found in the basolateral compartment and the cellular fraction after 4 hours when administered to the apical compartment. Additionally, not much M2 is found. Despite M2 becoming detectable in the apical compartment, LY335979 had minimal effect on the distribution of Seco Rapamycin following an apical dosage. In contrast, M2 and Seco Rapamycin are easily found in the apical compartment upon application of Seco Rapamycin to the basolateral compartment. Seco Rapamycin flow to the apical compartment is reduced by LY335679, while M2 levels in the apical and basolateral compartments are increased[1]. - Metabolic Conversion in Tissue Homogenates: In human liver, jejunal mucosal, and Caco-2 cell homogenates, Seco Rapamycin (Secorapamycin A) (20 μM) was converted to dihydro sirolimus (M2) in an NADPH-dependent manner. Ketoconazole (100 μM) did not inhibit M2 formation in these homogenates [1]. - Caco-2 Cell Monolayer Disposition: When Seco Rapamycin (Secorapamycin A) (20 μM) was applied to the apical compartment of Caco-2 cell monolayers, minimal drug was detected in the basolateral compartment after 4 hours, with limited M2 production. However, when applied basolaterally, both Seco Rapamycin (Secorapamycin A) and M2 were readily detected in the apical compartment. The P-glycoprotein inhibitor LY335679 reduced apical flux of Seco Rapamycin (Secorapamycin A) and increased M2 levels in both compartments [1]. |
| Enzyme Assay | Metabolic Activity in Tissue Homogenates: Human liver, jejunal mucosal, and Caco-2 cell homogenates were incubated with Seco Rapamycin (Secorapamycin A) (20 μM) in the presence of NADPH to assess M2 formation. Reactions were terminated after 30 minutes, and metabolites were analyzed by liquid chromatography. Ketoconazole (100 μM) was included in parallel experiments to evaluate cytochrome P450 inhibition [1]. |
| Cell Assay | aco-2 Cell Monolayer Permeability: Caco-2 cell monolayers grown on transwell inserts were treated with Seco Rapamycin (Secorapamycin A) (20 μM) apically or basolaterally for 4 hours. Samples from apical and basolateral compartments were collected and analyzed for Seco Rapamycin (Secorapamycin A) and M2 levels using LC-MS/MS. LY335979 (0.5 μM) was co-administered to investigate P-glycoprotein-mediated transport [1]. |
| ADME/Pharmacokinetics | - Metabolic Pathway: Seco Rapamycin (Secorapamycin A) undergoes NADPH-dependent conversion to M2 in human intestinal and hepatic tissues, suggesting involvement of cytochrome P450 enzymes. However, specific pharmacokinetic parameters (e.g., half-life, bioavailability) were not reported [1]. - Tissue Distribution: In Caco-2 cell monolayers, Seco Rapamycin (Secorapamycin A) exhibited limited apical-to-basolateral transport but efficient basolateral-to-apical flux, indicating potential efflux mechanisms [1]. |
| References |
[1]. Identification of a novel route of extraction of sirolimus in human small intestine: roles ofmetabolism and secretion. J Pharmacol Exp Ther. 2002 Apr;301(1):174-86. |
| Additional Infomation |
- Metabolite Background: Seco Rapamycin (Secorapamycin A) is the open-ring metabolite of sirolimus (rapamycin), formed during intestinal and hepatic metabolism [1]. - Study Purpose: The literature primarily investigates the intestinal extraction and metabolism of sirolimus, with Seco Rapamycin (Secorapamycin A) serving as a model compound to characterize metabolic pathways and transporter interactions [1]. - Transporter Interaction: P-glycoprotein modulation affected Seco Rapamycin (Secorapamycin A) distribution in Caco-2 cells, highlighting its potential as a P-glycoprotein substrate [1]. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0682 mL | 5.3410 mL | 10.6820 mL | |
| 5 mM | 0.2136 mL | 1.0682 mL | 2.1364 mL | |
| 10 mM | 0.1068 mL | 0.5341 mL | 1.0682 mL |