| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| Other Sizes |
| Targets |
RMC-5552 targets mTORC1 (mechanistic target of rapamycin complex 1), a central regulator of cell growth, proliferation, and metabolism. mTORC1 is activated by growth factors, nutrients, and energy status, and it phosphorylates downstream targets including pS6K (ribosomal protein S6 kinase) and p4EBP1 (eukaryotic initiation factor 4E-binding protein 1). By selectively inhibiting mTORC1 with high potency (IC50 = 0.14 nM for pS6K), RMC-5552 blocks protein synthesis and cell growth. The compound's selectivity for mTORC1 over mTORC2 (approximately 40-fold) reduces the risk of mTORC2-mediated side effects.
|
|---|---|
| ln Vitro |
Only in the presence of the FKBP12-FRB allosteric mode of RMC-5552 was recruitment of FKBP12 seen. At the interface between FKBP12 and the FRB domain of mTOR, the density of RMC-5552 is seen. Through the 4-aminopyrazolo[3,4-d] braid core, the “Manhattan chain” of mTOR, and the 2-aminobenzoxazole to E2190 and K2187 Reply[1], RMC-5552 forms hydrogen connections with the backbone of G2238 and V2240.
In vitro, RMC-5552 inhibits phosphorylation of mTORC1 downstream targets pS6K and p4EBP1 with IC50 values of 0.14 nM and 0.48 nM, respectively. It shows significantly reduced inhibition of pAKT (IC50 19 nM), with approximately 40-fold selectivity between mTORC1 and mTORC2. The compound exhibits anticancer activity in various cancer cell lines. Its potent and selective mTORC1 inhibition makes it a valuable tool for studying mTOR signaling and cancer biology. |
| ln Vivo |
RMC-5552 (1-10 mg/kg; intraperitoneal injection; once weekly; for 28 days) displayed anti-activity in a mouse MCF-7 human breast cancer xenograft model [1]. RMC-5552 demonstrates anti-activity in mice [1]. PK Parameters in Perfume 1 mg/kg[1] Compound Tmax (h) Cmax (ng/mL) Cmax (μM) AUClast (μg/mL × h) AUClast (μM × h) t1/2 (h) ) 38 RMC-5552 2.0 ± 0.0 5667 ± 1106 3.19 ± 0.62 46 089 ± 5320 25.9 ± 3.0 4.8 ± 0.4
In vivo, RMC-5552 has anticancer activity and potential for treating mTOR-driven cancers. By selectively inhibiting mTORC1, the compound may reduce tumor growth while minimizing mTORC2-related side effects. However, specific in vivo efficacy data for RMC-5552 have not been detailed in the available literature. The compound's high potency and selectivity for mTORC1 make it a promising candidate for further preclinical evaluation. |
| Enzyme Assay |
For in vitro kinase assays, mTORC1 activity is assessed using immunoprecipitated mTORC1 complexes or recombinant proteins incubated with substrates (such as S6K or 4EBP1) and ATP in kinase assay buffer. The test compound is added at various concentrations (0.001-1000 nM). Substrate phosphorylation is measured by Western blotting using phospho-specific antibodies or by using radioactive ATP incorporation. IC50 values are calculated by fitting dose-response curves. Selectivity for mTORC1 over mTORC2 is assessed by measuring pAKT (Ser473) phosphorylation, which is mTORC2-dependent.
|
| Cell Assay |
For cell-based assays, cancer cell lines are treated with RMC-5552 at concentrations ranging from 0.001-10 µM for 2-24 hours. mTORC1 activity is assessed by measuring the phosphorylation of pS6K (Thr389) and p4EBP1 (Thr37/46) by Western blotting. mTORC2 activity is assessed by measuring pAKT (Ser473). Cell viability and proliferation are measured using MTT or CellTiter-Glo assays. Apoptosis can be assessed by caspase activity or Annexin V staining.
|
| Animal Protocol |
Animal/Disease Models: Female Balb/c nude mice (6-8 weeks old) injected with MCF-7 cells [1]
Doses: 1 mg/kg, 3 mg/kg, 10 mg/kg. Route of Administration: intraperitoneal (ip) injection; once a week; for 28 days Experimental Results: resulted in tumor volume reduction. For in vivo efficacy studies, immunodeficient mice are implanted with cancer xenografts. When tumors reach a predetermined size, mice are randomized and treated with RMC-5552 via oral or intraperitoneal administration at doses determined from pharmacokinetic studies. Tumor volumes are measured twice weekly. At study endpoint, tumors are collected for Western blot analysis of pS6K and p4EBP1 phosphorylation to confirm mTORC1 inhibition. |
| ADME/Pharmacokinetics |
RMC-5552 is soluble in DMSO. Storage is recommended at -20°C for long-term stability. The compound's high molecular weight (1778.13) suggests it may have complex pharmacokinetic properties typical of large molecules. Further detailed PK parameters including half-life, oral bioavailability, and tissue distribution would be required for in vivo studies.
|
| Toxicity/Toxicokinetics |
Toxicological data for RMC-5552 have not been extensively reported. As a research compound, it is intended for laboratory use only and is not for human or veterinary use. Standard safety precautions should be followed when handling this compound. Comprehensive toxicology studies would be required before any clinical development.
|
| References | |
| Additional Infomation |
The mTORC1 kinase inhibitor RMC-5552 is a dual steric hindrance inhibitor that inhibits target of rapamycin (mTOR) complex 1 (mTOR complex 1; mTORC1) and possesses potential antitumor activity. After administration, RMC-5552 selectively targets, binds to, and inhibits the serine/threonine kinase activity of mTORC1, leading to a decrease in the expression of mRNAs required for cell cycle progression, which may induce cell cycle arrest and tumor cell apoptosis. mTORC1 phosphorylates various transcription factors, such as ribosomal protein S6 kinase β-1 (S6K1) and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), which stimulate protein synthesis and regulate cell growth, proliferation, migration, and survival. RMC-5552 inhibits the phosphorylation of the tumor suppressor gene 4EBP1, inducing apoptosis and reducing the proliferation of mTORC1-positive tumor cells. mTORC1 is a serine/threonine kinase whose expression is upregulated in certain tumor cell types. It plays a crucial role in the PI3K/Akt/mTOR signaling pathway, which is frequently aberrantly activated in cancer cells, promoting cell growth, survival, and resistance to chemotherapy and radiotherapy. Selective inhibition of mTORC1 improves the poor clinical tolerability of drugs that simultaneously inhibit the mTORC2 complex.
RMC-5552 is a potent and selective mTORC1 inhibitor with IC50 values of 0.14 nM (pS6K) and 0.48 nM (p4EBP1), and approximately 40-fold selectivity over mTORC2. It exhibits anticancer activity. RMC-5552 is used in research to study mTOR signaling and cancer biology. It is a research tool and is not approved for clinical use. |
| Molecular Formula |
C93H136N10O24
|
|---|---|
| Molecular Weight |
1778.13
|
| Exact Mass |
1776.972
|
| CAS # |
2382768-62-7
|
| PubChem CID |
162640850
|
| Appearance |
White to off-white solid powder
|
| LogP |
7
|
| Hydrogen Bond Donor Count |
6
|
| Hydrogen Bond Acceptor Count |
30
|
| Rotatable Bond Count |
38
|
| Heavy Atom Count |
127
|
| Complexity |
3460
|
| Defined Atom Stereocenter Count |
16
|
| SMILES |
C1C=C(C)[C@H](C[C@@]2(CC[C@H]([C@@](O)(O2)C(C(N2CCCC[C@@]2([H])C(=O)O[C@]([H])([C@@H](C[C@@H]2CC[C@H]([C@H](OC)C2)OC(=O)NCCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)N2CC3=CC=C(CN4N=C(C5C6N=C(N)OC=6C=CC=5)C5C(N)=NC=NC4=5)C=C3CC2)C)C[C@@H](O)[C@@H](C=C([C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)C=CC=1)C)C)=O)=O)C)[H])OC |c:1,t:114,128,130|
|
| InChi Key |
IUTYTXDIGUNPAA-GKVGALOGSA-N
|
| InChi Code |
InChI=1S/C93H136N10O24/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/h11-13,16-17,20,22-23,26,49,51,53,58-59,61-63,65-66,71,73-74,76-79,84-85,104,107,112H,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+,74-,76-,77+,78+,79-,84-,85+,93-/m1/s1
|
| Chemical Name |
[(1R,2R,4S)-2-methoxy-4-[(2R)-2-[(1R,9S,12S,14R,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,14,18-trihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-2,3,10,20-tetraoxo-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraen-12-yl]propyl]cyclohexyl] 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
|
| 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 |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~166.67 mg/mL (~93.73 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (2.81 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 5 mg/mL (2.81 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 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 | 0.5624 mL | 2.8119 mL | 5.6239 mL | |
| 5 mM | 0.1125 mL | 0.5624 mL | 1.1248 mL | |
| 10 mM | 0.0562 mL | 0.2812 mL | 0.5624 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
