2. PI3K/Akt/mTOR Autophagy
  3. mTOR Autophagy
  4. RapaLink-1

RapaLink-1, the third-generation bivalent mTOR inhibitor, combines Rapamycin (HY-10219) with MLN0128 (HY-13328, a second-generation mTOR kinase inhibitor) by an inert chemical linker. RapaLink-1 shows better efficacy than Rapamycin or mTOR kinase inhibitors (TORKi), potently blocking cancer-derived, activating mutants of mTOR. RapaLink-1 can cross the blood-brain barrier. RapaLink-1 binding to FKBP12 results in targeted and durable inhibition of mTORC1. RapaLink-1 plays an antithrombotic role in antiphospholipid syndrome by improving autophagy. Anticancer activity.

For research use only. We do not sell to patients.

CAS No. : 1887095-82-0

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Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
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Customer Review

Based on 13 publication(s) in Google Scholar

Other Forms of RapaLink-1:

RapaLink-1 Related Antibodies

Top Publications Citing Use of Products

    RapaLink-1 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 Oct 20;16(1):9250.  [Abstract]

    qRT-PCR analysis of 1 C enzyme mRNA expression in HLFs either left untreated or treated with TGF-β in the presence or absence of the mTORC1 inhibitor Rapalink-1 (2 nM).

    RapaLink-1 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 Oct 20;16(1):9250.  [Abstract]

    Western blot analysis of 1 C enzyme protein expression in HLFs treated with TGF-β for the indicated intervals in the presence or absence of Rapalink-1 (2 nM).

    RapaLink-1 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2024 Jul 19;15(1):6076.  [Abstract]

    Cell viability as percentage change from control of KRASG12C mutant cell lines treated for 72 h with BYL719 1 µM, MK2206 1 µM, Rapamycin 10 nM, RMC-6272 1 nM, RapaLink-1 10 nM, Adagrasib 100 nM, RM-018 100 nM, or combination treatments as indicated.

    RapaLink-1 purchased from MedChemExpress. Usage Cited in: Int J Mol Sci. 2023 Jan 20;24(3):2055.

    Rapalink-1 (10 nM) alone and in combination with CR-1-B-R1 or Zotatifin increased apoptosis in the two cell lines.

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    mTOR mTORC1 mTORC2

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    Description

    RapaLink-1, the third-generation bivalent mTOR inhibitor, combines Rapamycin (HY-10219) with MLN0128 (HY-13328, a second-generation mTOR kinase inhibitor) by an inert chemical linker. RapaLink-1 shows better efficacy than Rapamycin or mTOR kinase inhibitors (TORKi), potently blocking cancer-derived, activating mutants of mTOR. RapaLink-1 can cross the blood-brain barrier. RapaLink-1 binding to FKBP12 results in targeted and durable inhibition of mTORC1. RapaLink-1 plays an antithrombotic role in antiphospholipid syndrome by improving autophagy. Anticancer activity[1][2].

    IC50 & Target[1]

    mTOR

     

    In Vitro

    RapaLink-1 (0-200 nM; 3 days) shows U87MG cells growth inhibition[1].
    RapaLink-1 (0-12.5 nM; 48 hours) arrests U87MG cells at G0/G1[1].
    RapaLink-1 selectively inhibits p-RPS6S235/236 and p-4EBP1T37/46 at doses as low as 1.56 nM[1].
    Rapalink-1 (100 nM; 24 to 96 hours) suppressed renal cell carcinoma (RCC) cell proliferation by inducing apoptosis and cell cycle arrest[2].
    RapaLink-1 exploits the unique juxtaposition of two drug-binding pockets to create a bivalent interaction. RapaLink-1 overcomes resistance to existing first- and second-generation inhibitors[3].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    RapaLink-1 Related Antibodies

    Cell Proliferation Assay[1]

    Cell Line: U87MG cells
    Concentration: 0-200 nM
    Incubation Time: 3 days
    Result: Showed growth inhibition.

    Cell Cycle Analysis[1]

    Cell Line: U87MG cells
    Concentration: 0-12.5 nM
    Incubation Time: 48 hours
    Result: Arrested cells at G0/G1.

    Western Blot Analysis[1]

    Cell Line: U87MG cells
    Concentration: 0.39-12.5 nM
    Incubation Time: 3 hours
    Result: Selectively inhibited p-RPS6S235/236 and p-4EBP1T37/46 at doses as low as 1.56 nM. The mTORC2 targets p-AKTS473, p-SGK1S78, and p-NDRG1T346, and the p-AKTS473 target p-GSK3βS9 was inhibited only at high doses.
    In Vivo

    RapaLink-1 (i.p.; every 5 days for 25 days, then once a week for 11 week) shows potent anti-tumor efficacy[1].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Model: BALB/ Cnu/nu mice bearing U87MG intracranial xenografts[1]
    Dosage: 1.5 mg/kg
    Administration: I.p.; every 5 days for 25 days, then once a week for 11 week
    Result: Led to initial regression and subsequent stabilization of tumor size.
    Molecular Weight

    1784.14

    Formula

    C91H138N12O24
    CAS No.
    Appearance

    Solid

    Color

    White to light yellow

    SMILES

    NC1=C(C2=NC=N1)C(C3=CC=C(O4)C(N=C4N)=C3)=NN2CCCCNC(CCOCCOCCOCCOCCOCCOCCOCCOCCN(N=N5)C=C5COCCO[C@H](CC[C@H]6C[C@H]([C@@](CC([C@@H](/C=C([C@H]([C@H](C([C@@H](C[C@@H]7C)C)=O)OC)O)\C)C)=O)([H])OC([C@@](CCCC8)([H])N8C(C([C@@]9(O[C@@](C[C@@H](/C(C)=C/C=C/C=C/7)OC)([H])CC[C@H]9C)O)=O)=O)=O)C)[C@@H](C6)OC)=O
    Shipping

    Room temperature in continental US; may vary elsewhere.
    Storage

    -20°C, sealed storage, away from moisture

    *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 100 mg/mL (56.05 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    H2O : < 0.1 mg/mL (insoluble)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 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
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

    • Molarity Calculator

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    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

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    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  10% DMSO    90% Corn Oil

      Solubility: ≥ 5 mg/mL (2.80 mM); Clear solution

      This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL Corn oil, and mix evenly.

    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

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    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
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    +
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    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).

    *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.65%

    SDS (393 KB)

    COA (255 KB) HNMR (236 KB) RP-HPLC (271 KB) MS (72 KB)

    Handling Instructions (2659 KB)
    References

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 0.5605 mL 2.8025 mL 5.6049 mL 14.0124 mL
    5 mM 0.1121 mL 0.5605 mL 1.1210 mL 2.8025 mL
    10 mM 0.0560 mL 0.2802 mL 0.5605 mL 1.4012 mL
    15 mM 0.0374 mL 0.1868 mL 0.3737 mL 0.9342 mL
    20 mM 0.0280 mL 0.1401 mL 0.2802 mL 0.7006 mL
    25 mM 0.0224 mL 0.1121 mL 0.2242 mL 0.5605 mL
    30 mM 0.0187 mL 0.0934 mL 0.1868 mL 0.4671 mL
    40 mM 0.0140 mL 0.0701 mL 0.1401 mL 0.3503 mL
    50 mM 0.0112 mL 0.0560 mL 0.1121 mL 0.2802 mL
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    RapaLink-1 Related Classifications

    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

    Keywords:

    RapaLink-11887095-82-0RapaLink1RapaLink 1mTORAutophagyMammalian target of Rapamycinresistancemutationthird-generationblood-brainbarrieranticancerbivalentregressionInhibitorinhibitorinhibit

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