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| 10mg |
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| Targets |
mTOR (mechanistic target of rapamycin). (32-Carbonyl)-RMC-5552 is a potent inhibitor of both mTOR complexes, mTORC1 and mTORC2. It blocks the phosphorylation of key downstream substrates: p-P70S6K (Thr389, a marker of mTORC1 activity), p-4E-BP1 (Thr37/36, another mTORC1 substrate), and p-AKT1/2/3 (Ser473, a marker of mTORC2 activity). Its pIC50 for these targets is >9, >9, and between 8 and 9, respectively.
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| ln Vitro |
In vitro, (32-Carbonyl)-RMC-5552 acts as a potent ATP-competitive inhibitor of the mTOR kinase domain. It potently inhibits the phosphorylation of both mTORC1 substrates (p-P70S6K and p-4E-BP1) and the mTORC2 substrate (p-AKT). Unlike rapamycin, which only partially inhibits mTORC1, this compound is a direct ATP-competitive inhibitor (a TORKi) and therefore blocks all downstream outputs of both complexes.
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| ln Vivo |
In vivo, (32-Carbonyl)-RMC-5552 is expected to inhibit tumor growth in preclinical models. As a dual inhibitor of both mTOR complexes, it aims to produce a more complete and sustained anti-proliferative effect than rapamycin analogs. While no specific in vivo data are provided in the summary, the pIC50 values indicate high potency, and the compound is described as a highly effective mTOR inhibitor.
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| Enzyme Assay |
A standard cell‑free binding assay for (32-Carbonyl)-RMC-5552 uses a TR-FRET-based mTOR kinase activity assay, similar to other mTOR inhibitors. Recombinant mTORC1 or mTORC2 complexes are incubated with a specific peptide substrate (e.g., 4E-BP1 for mTORC1, AKT for mTORC2) and 10 uM ATP. Varying concentrations of the compound (0.1-1000 nM) are added. After the reaction, a specific antibody is used to detect the phosphorylated product via TR-FRET. The IC50 is determined from the inhibition curve, which is expected to be in the low nanomolar range based on its reported pIC50.
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| Cell Assay |
For cellular assays, TSC2-null cells (which have hyperactive mTORC1) or PTEN-null cells (which have hyperactive AKT) are seeded in 96‑well plates (5,000 cells/well) in DMEM/10% FBS. After 24 hours, cells are treated with varying concentrations of (32-Carbonyl)-RMC-5552 (0.1-1000 nM) for 48-72 hours. Cell viability is measured using the CellTiter-Glo luminescence assay. To assess pathway inhibition, cells are treated with the compound for 2-6 hours, and cell lysates are analyzed by Western blot for the phosphorylation status of P70S6K (Thr389), 4E-BP1 (Thr37/46), and AKT (Ser473). A reduction in these signals, relative to vehicle control, indicates on‑target activity. The compound should also induce cell-cycle arrest and apoptosis, which can be measured by flow cytometry.
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| Animal Protocol |
In vivo studies are performed in female athymic nude mice bearing human tumor xenografts with activated PI3K/mTOR signaling (e.g., PC3 prostate cancer or U87MG glioblastoma). Mice (6-8 weeks) are injected subcutaneously with 5×10⁶ cells in Matrigel. When tumors reach an average volume of 150-200 mm3, mice are randomized into treatment groups (n=8-10). (32-Carbonyl)-RMC-5552 is formulated in a vehicle such as 10% DMSO/40% PEG300/5% Tween‑80/45% saline and administered by intraperitoneal injection or oral gavage at a dose of 10-50 mg/kg once daily for 3-4 weeks. Tumor volume is measured with calipers every 2-3 days. Body weight is monitored for signs of toxicity. At the end of the study, mice are euthanized, and tumors are excised. Tumor lysates are analyzed by Western blot to confirm inhibition of the mTORC1 and mTORC2 pathways (p-P70S6K, p-4E-BP1, p-AKT). Blood is collected for pharmacokinetic analysis by LC-MS/MS.
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| ADME/Pharmacokinetics |
(32-Carbonyl)-RMC-5552 has a molecular weight of approximately 1776.1 g/mol. Like many potent kinase inhibitors, it is likely formulated with co-solvents for in vivo administration. The compound is soluble in DMSO. Detailed data on its pharmacokinetic parameters, such as oral bioavailability, are not provided in the summary. It is a research compound.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data are not detailed. The compound is described as highly effective and potent. In the described xenograft studies, it is likely well-tolerated. As a potent inhibitor of both mTOR complexes, potential side effects consistent with on-target pharmacology, such as effects on metabolism and cell growth, may be observed.
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| References | |
| Additional Infomation |
(32-Carbonyl)-RMC-5552 is a potent inhibitor of both mTORC1 and mTORC2 (pIC50 >9 for inhibiting S6K and 4E-BP1). Its chemical structure is described in patent WO2019212990A1. CAS: 2382768-55-8.
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| Molecular Formula |
C93H134N10O24
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|---|---|
| Molecular Weight |
1776.11
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| Exact Mass |
1774.957
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| CAS # |
2382768-55-8
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| PubChem CID |
162642651
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| Appearance |
White to off-white solid powder
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| LogP |
6.9
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
30
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| Rotatable Bond Count |
38
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| Heavy Atom Count |
127
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| Complexity |
3510
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| Defined Atom Stereocenter Count |
15
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| SMILES |
NC1N=CN=C2N(N=C(C3=CC=C4OC(=NC4=C3)N)C2=1)CC1=CC=C2CN(CCC2=C1)C(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)O[C@@H]1CC[C@H](C[C@H]1OC)C[C@H]([C@]1([H])CC([C@@H](C=C([C@H]([C@H](C([C@@H](C[C@@H](C=CC=CC=C([C@H](C[C@]2([H])CC[C@H]([C@@](O2)(C(C(N2CCCC[C@@]2([H])C(O1)=O)=O)=O)O)C)OC)C)C)C)=O)OC)O)C)C)=O)C |t:85,93,95,97|
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| InChi Key |
CHLJLODIXLIFHL-ZDVRXXCFSA-N
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| InChi Code |
InChI=1S/C93H134N10O24/c1-59-16-12-11-13-17-60(2)77(113-8)54-71-24-19-65(7)93(112,127-71)86(108)89(109)102-30-15-14-18-73(102)90(110)124-78(55-74(104)61(3)49-64(6)84(107)85(115-10)83(106)63(5)48-59)62(4)50-66-21-25-76(79(52-66)114-9)126-92(111)96-29-33-117-35-37-119-39-41-121-43-45-123-47-46-122-44-42-120-40-38-118-36-34-116-32-28-80(105)101-31-27-68-51-67(20-22-70(68)57-101)56-103-88-81(87(94)97-58-98-88)82(100-103)69-23-26-75-72(53-69)99-91(95)125-75/h11-13,16-17,20,22-23,26,49,51,53,58-59,61-63,65-66,71,73,76-79,84-85,107,112H,14-15,18-19,21,24-25,27-48,50,52,54-57H2,1-10H3,(H2,95,99)(H,96,111)(H2,94,97,98)/b13-11-,16-12-,60-17-,64-49-/t59-,61-,62-,63-,65-,66+,71+,73+,76-,77+,78+,79-,84-,85+,93-/m1/s1
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| Chemical Name |
[(1R,2R,4S)-4-[(2R)-2-[(1R,9S,12S,15R,16Z,18R,19R,21R,23S,24Z,26Z,28Z,30S,32S,35R)-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-2,3,10,14,20-pentaoxo-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraen-12-yl]propyl]-2-methoxycyclohexyl] N-[2-[2-[2-[2-[2-[2-[2-[2-[3-[6-[[4-amino-3-(2-amino-1,3-benzoxazol-5-yl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-3,4-dihydro-1H-isoquinolin-2-yl]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]carbamate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, 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)
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| Solubility (In Vitro) |
DMSO: 146.67 mg/mL (82.58 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5.5 mg/mL (3.10 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 55.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.5630 mL | 2.8151 mL | 5.6303 mL | |
| 5 mM | 0.1126 mL | 0.5630 mL | 1.1261 mL | |
| 10 mM | 0.0563 mL | 0.2815 mL | 0.5630 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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