| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
mTORC1 (Mechanistic Target of Rapamycin Complex 1). RMC-6272 is a selective mTORC1 inhibitor. It binds to both the FKBP12 and the FKBP12-rapamycin binding (FRB) domain of mTOR to inhibit the complex. It displays potent and selective (>10-fold) inhibition of mTORC1 over mTORC2, a property that distinguishes it from first-generation mTOR inhibitors.
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| ln Vitro |
In several TSC1 or TSC2 mutant tumor cell lines, RMC-6272 showed more effective growth suppression than Rapamycin. In TSC1 or TSC2 mutant cells, RMC-6272 induced a more significant growth inhibition than in wild-type cells. p4E-BP1T37/46 is nearly entirely inhibited by RMC-6272 at ~1 nM, while pS6S240/244 levels are equally inhibited by rapamycin and RM compounds [1].
In vitro, RMC-6272 demonstrates potent inhibition of mTORC1, leading to a reduction in downstream signaling. Compared to rapamycin, RMC-6272 shows enhanced inhibition of mTORC1 and induces increased cell death in TSC2‑null tumors, which are highly sensitive to mTORC1 dysregulation. This suggests that its unique binding mode may block functions of mTORC1 that rapamycin cannot fully inhibit. Its selectivity for mTORC1 over mTORC2 minimizes off-target effects on pathways related to cell survival and proliferation mediated by mTORC2. |
| ln Vivo |
After four weeks of treatment, RMC-6272 dramatically decreased the burden of kidney tumors in Tsc2+/- A/J mice. Tumor regrowth was measured two months after treatment ended, and the RMC-6272 group showed a significant reduction in tumor burden as compared to the rapamycin and MLN0128 groups [1].
In vivo, RMC-6272 has been evaluated in mouse models of cancer, particularly in tumors with hyperactive mTORC1 signaling, such as those lacking the tumor suppressor TSC2. It effectively inhibits tumor growth by blocking the mTORC1 pathway. Its selectivity for mTORC1 over mTORC2 is predicted to provide a better therapeutic index by reducing the metabolic side effects associated with pan-mTOR inhibitors. |
| Enzyme Assay |
Standard cell‑free binding assays for RMC-6272 can be performed using a TR-FRET (Time-Resolved Fluorescence Resonance Energy Transfer) assay to measure mTORC1 kinase activity. The assay is set up by incubating recombinant mTORC1 complex (5-10 ng) in a reaction buffer (50 mM HEPES, pH 7.5, 5 mM MgCl2, 1 mM DTT) containing a specific peptide substrate (e.g., 4E-BP1) and 10 uM ATP. Varying concentrations of RMC-6272 (0.1-1000 nM) are added, and the reaction proceeds for 60-90 minutes. After the reaction, an antibody specific to the phosphorylated substrate is used to detect the product via TR-FRET. The IC50 is calculated from the inhibition curve. For selectivity, a parallel assay is set up with the recombinant mTORC2 complex using its specific substrate (e.g., AKT). A separate cell‑free binding assay can measure the interaction with FKBP12, which is part of its inhibitory mechanism.
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| Cell Assay |
For cellular assays, TSC2‑null cancer cells (e.g., ELT3 cells) are seeded in 96‑well plates (5,000 cells/well) in DMEM/10% FBS. After 24 hours, cells are treated with varying concentrations of RMC-6272 (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 RMC-6272 for 2-6 hours, and cell lysates are analyzed by Western blot for markers of mTORC1 activity, including p-S6K (Thr389) and p-4E-BP1 (Thr37/46). A reduction in the ratio of phosphorylated to total protein indicates on-target activity. The ability of RMC-6272 to induce cell death in TSC2‑null cells can be assessed by flow cytometry using Annexin V/PI staining.
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| Animal Protocol |
In vivo studies are performed in female athymic nude mice bearing ELT3 (TSC2‑null) xenografts. Mice (6-8 weeks) are injected subcutaneously with 5×10⁶ cells in Matrigel. When tumors reach an average volume of 200 mm3, mice are randomized into treatment groups (n=8). RMC-6272 is formulated in a vehicle such as 10% DMSO/40% PEG300/5% Tween‑80/45% saline and administered by oral gavage at doses of 10-50 mg/kg once daily for 3-4 weeks. Tumor volume is measured with calipers every 2-3 days. Body weight is also monitored to assess general toxicity. At the end of the study, the mice are euthanized, and tumors are excised. Tumor lysates are analyzed by Western blot to confirm inhibition of the mTORC1 pathway (p-S6K, p-4E-BP1). Blood is collected for pharmacokinetic analysis of RMC-6272 by LC-MS/MS.
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| ADME/Pharmacokinetics |
RMC-6272 is a small molecule with a high molecular weight (approximately 1850 Da). It is formulated for oral administration in research settings and has shown good activity in mouse xenograft models. Its high molecular weight may present challenges for standard oral bioavailability, but the data suggest sufficient exposure is achieved. The compound is soluble in DMSO.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data for RMC-6272 are not detailed in the provided sources. In the described xenograft studies, the compound was well-tolerated, as no significant body weight loss or overt signs of toxicity were reported. Its selective mechanism aims to minimize off-target effects, which may contribute to a favorable preclinical safety profile.
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| References | |
| Additional Infomation |
RMC-6272 (RM-006) is a bi‑steric, selective mTORC1 inhibitor with >10‑fold selectivity over mTORC2. It is used as a research tool for studying the mTOR pathway and for developing targeted cancer therapies. It has not entered clinical trials and is not FDA-approved. CAS: 2382769-46-0.
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| Molecular Formula |
C95H141FN6O27S
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|---|---|
| Molecular Weight |
1850.22
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| Exact Mass |
1849.958
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| CAS # |
2382769-46-0
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| PubChem CID |
162642652
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
6.9
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
30
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| Rotatable Bond Count |
41
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| Heavy Atom Count |
130
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| Complexity |
3660
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| Defined Atom Stereocenter Count |
16
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| SMILES |
C(C1C=CC(S(=O)(=O)CCNC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)O[C@@H]2CC[C@@H](C[C@H]([C@]3([H])C[C@H]([C@@H](C=C([C@H]([C@H](C([C@@H](C[C@@H](C=CC=CC=C(C)[C@@H](OC)C[C@]4([H])CC[C@@H](C)[C@](O4)(O)C(=O)C(=O)N4CCCC[C@@]4([H])C(=O)O3)C)C)=O)OC)O)C)C)O)C)C[C@H]2OC)=C(F)C=1C)(N1CCOC2=CC=C(C3=CN=C(N)C=C3)C=C2C1)=O |c:66,t:54,62,64,&1:43,46,48,49,52,53,56,57,59,61,69,73,77,79,91,107|
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| InChi Key |
SBCMKKFTXRBACH-URWOFZDBSA-N
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| InChi Code |
InChI=1S/C95H141FN6O27S/c1-62-17-13-12-14-18-63(2)80(115-9)58-74-24-20-68(7)95(112,129-74)90(107)92(109)102-33-16-15-19-76(102)93(110)127-81(59-77(103)64(3)54-67(6)88(106)89(117-11)87(105)66(5)53-62)65(4)55-70-21-26-79(82(56-70)116-10)128-94(111)99-31-36-119-39-41-121-43-45-123-47-49-125-51-50-124-48-46-122-44-42-120-40-38-118-35-30-85(104)98-32-52-130(113,114)83-28-25-75(69(8)86(83)96)91(108)101-34-37-126-78-27-22-71(57-73(78)61-101)72-23-29-84(97)100-60-72/h12-14,17-18,22-23,25,27-29,54,57,60,62,64-66,68,70,74,76-77,79-82,88-89,103,106,112H,15-16,19-21,24,26,30-53,55-56,58-59,61H2,1-11H3,(H2,97,100)(H,98,104)(H,99,111)/b14-12+,17-13+,63-18+,67-54+/t62-,64-,65-,66-,68-,70+,74+,76+,77-,79-,80+,81+,82-,88-,89+,95-/m1/s1
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| 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-[2-[4-[7-(6-aminopyridin-3-yl)-3,5-dihydro-2H-1,4-benzoxazepine-4-carbonyl]-2-fluoro-3-methylphenyl]sulfonylethylamino]-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 |
| 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: 25 mg/mL (13.51 mM)
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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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.5405 mL | 2.7024 mL | 5.4048 mL | |
| 5 mM | 0.1081 mL | 0.5405 mL | 1.0810 mL | |
| 10 mM | 0.0540 mL | 0.2702 mL | 0.5405 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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