| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
RapaLink-1 targets the mechanistic target of rapamycin (mTOR). It binds to FKBP12, which results in targeted and durable inhibition of mTORC1. By combining Rapamycin and MLN0128, it creates a bivalent interaction that effectively blocks cancer-derived mTOR activation mutants. This dual mechanism allows it to overcome resistance seen with first-generation mTOR inhibitors.
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| ln Vitro |
RapaLink-1 (0-200 nM; 3 days) inhibits U87MG cell proliferation [1]. In 48 hours, RapaLink-1 (0–12.5 nM) arrests U87MG cells at G0/G1[1]. At dosages as low as 1.56 nM, RapaLink-1 selectively suppresses p-RPS6S235/236 and p-4EBP1T37/46 [1]. By causing apoptosis and cell cycle arrest, Rapalink-1 (100 nM; 24 to 96 hours) suppresses the proliferation of renal cell carcinoma (RCC) cells [2]. RapaLink-1 generates bivalent connections by taking advantage of the distinct arrangement of two drug-binding pockets. Resistance to current first- and second-generation inhibitors is addressed by RapaLink-1 [3].
In vitro, RapaLink-1 inhibits cancer cell progression. It arrests U87MG cells at G0/G1 in 48 hours. It suppresses the proliferation of renal cell carcinoma (RCC) cells. It shows superior efficacy in inhibiting both wild-type and mutant forms of mTOR compared to other inhibitors. |
| ln Vivo |
Intraperitoneal injection RapaLink-1, administered every five days for 25 days, and thereafter weekly for 11 weeks, has demonstrated strong anti-tumor activity [1].
In vivo, RapaLink-1 has demonstrated anticancer activity. It has shown efficacy against resistant mutants of malignant brain tumors. It plays an antithrombotic role in antiphospholipid syndrome by improving autophagy. Its binding to FKBP12 results in targeted and durable inhibition of mTORC1. |
| Enzyme Assay |
Non-cellular assays for RapaLink-1 involve measuring its inhibition of mTOR kinase activity. These assays use recombinant mTOR and a peptide substrate. The enzyme is incubated with the substrate and ATP in the presence of varying concentrations of RapaLink-1. The phosphorylation of the substrate is measured to determine the IC50. Its binding to FKBP12 can be assessed using surface plasmon resonance (SPR).
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: U87MG Cell Tested Concentrations: 0-200 nM Incubation Duration: 3 days Experimental Results: demonstrated growth inhibition. Cell cycle analysis[1] Cell Types: U87MG Cell Tested Concentrations: 0-12.5 nM Incubation Duration: 48 hrs (hours) Experimental Results: G0/G1 cell arrest. Western Blot Analysis[1] Cell Types: U87MG Cell Tested Concentrations: 0.39-12.5 nM Incubation Duration: 3 hrs (hours) Experimental Results: Selective inhibition of p-RPS6S235/236 and p-4EBP1T37/46 at doses as low as 1.56 nM. mTORC2 targets p-AKTS473, p-SGK1S78 and p-NDRG1T346, and p-AKTS473 target p-GSK3βS9 is inhibited only at high doses. In vitro cellular assays for RapaLink-1 are conducted in cancer cell lines such as U87MG and renal cell carcinoma (RCC) cells. Cells are treated with the compound, and cell cycle analysis is performed by flow cytometry. Cell proliferation is measured using MTT or CellTiter-Glo assays. The phosphorylation of mTOR downstream targets (e.g., S6K1, 4E-BP1) is measured by Western blot to confirm pathway inhibition. |
| Animal Protocol |
Animal/Disease Models: BALB/Cnu/nu (nude) mice bearing U87MG intracranial xenografts [1]
Doses: 1.5 mg/kg Route of Administration: intraperitoneal (ip) injection; every 5 days for 25 days, then weekly for 11 Weekly Experimental Results: Resulting in initial regression and subsequent stabilization of tumor size. In vivo animal experiments with RapaLink-1 are conducted in mouse xenograft models of cancer, particularly for malignant brain tumors. Tumor-bearing mice are administered RapaLink-1, and tumor growth is monitored. Tumor tissues are harvested for analysis of mTOR pathway inhibition and apoptosis markers. Its effects on thrombosis can be studied in models of antiphospholipid syndrome. |
| ADME/Pharmacokinetics |
RapaLink-1 is a potent inhibitor of mTOR. It is soluble in DMSO and is typically stored as a powder at -20°C. Its pharmacokinetic properties, such as half-life and bioavailability, would need to be characterized for in vivo use.
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| Toxicity/Toxicokinetics |
Toxicological data for RapaLink-1 are not extensively published. The compound is intended for research use only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling this compound.
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| References |
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| Additional Infomation |
RapaLink-1 is a third-generation bivalent mTOR inhibitor. It combines Rapamycin and MLN0128 and demonstrates efficacy against resistant cancer mutants. It binds to FKBP12 and inhibits mTORC1. It has shown anticancer and antithrombotic activity in preclinical studies.
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| Molecular Formula |
C₉₁H₁₃₈N₁₂O₂₄
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|---|---|
| Molecular Weight |
1784.14
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| Exact Mass |
1797.01
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| CAS # |
1887095-82-0
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| Related CAS # |
Rapamycin;53123-88-9
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| PubChem CID |
154808065
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| Appearance |
White to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.592
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| LogP |
1.85
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
32
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| Rotatable Bond Count |
45
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| Heavy Atom Count |
127
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| Complexity |
3370
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| Defined Atom Stereocenter Count |
15
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| SMILES |
C[C@@H]1CC[C@H]2C[C@@H](C(=CC=C/C=C/[C@H](C[C@H](C(=O)[C@@H]([C@@H](/C(=C/[C@H](C(=O)C[C@H](OC(=O)[C@@H]3CCCCN3C(=O)C(=O)[C@@]1(O2)O)[C@H](C)C[C@@H]4CC[C@H]([C@@H](C4)OC)OCCOCC5=CN(N=N5)CCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)NCCCCN6C7=NC=NC(=C7C(=N6)C8=CC9=C(C=C8)OC(=N9)N)N)C)/C)O)OC)C)C)C)OC
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| InChi Key |
QDOGZMBPRITPMZ-SLBWSSLNSA-N
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| InChi Code |
InChI=1S/C91H138N12O24/c1-60-18-12-11-13-19-61(2)76(112-8)55-70-24-21-66(7)91(111,127-70)85(108)88(109)102-29-16-14-20-72(102)89(110)125-77(56-73(104)62(3)51-65(6)83(107)84(114-10)82(106)64(5)50-60)63(4)52-67-22-25-75(78(53-67)113-9)124-49-48-123-58-69-57-101(100-98-69)31-33-116-35-37-118-39-41-120-43-45-122-47-46-121-44-42-119-40-38-117-36-34-115-32-27-79(105)94-28-15-17-30-103-87-80(86(92)95-59-96-87)81(99-103)68-23-26-74-71(54-68)97-90(93)126-74/h11-13,18-19,23,26,51,54,57,59-60,62-64,66-67,70,72,75-78,83-84,107,111H,14-17,20-22,24-25,27-50,52-53,55-56,58H2,1-10H3,(H2,93,97)(H,94,105)(H2,92,95,96)/b13-11?,18-12+,61-19?,65-51+/t60-,62-,63-,64-,66-,67+,70+,72+,75-,76+,77+,78-,83-,84+,91-/m1/s1
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| Chemical Name |
N-[4-[4-amino-3-(2-amino-1,3-benzoxazol-5-yl)pyrazolo[3,4-d]pyrimidin-1-yl]butyl]-3-[2-[2-[2-[2-[2-[2-[2-[2-[4-[2-[(1R,2R,4S)-4-[(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,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]oxyethoxymethyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanamide
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| Synonyms |
RapaLink1 RapaLink 1
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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 : ~178 mg/mL (~99.77 mM)
H2O : < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (2.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
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 | 0.5605 mL | 2.8025 mL | 5.6049 mL | |
| 5 mM | 0.1121 mL | 0.5605 mL | 1.1210 mL | |
| 10 mM | 0.0560 mL | 0.2802 mL | 0.5605 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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