RapaLink-1
Based on 14 publication(s) in Google Scholar
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.
- Purity: 99.65%
- CAS No.: 1887095-82-0
- Formula: C91H138N12O24
- Molecular Weight:1784.14
-
Storage:
-20°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Biological Activity
-
Chemical Information
-
Solvent & Solubility
- Purity & Documentation
- References
-
Help & FAQs
Publications Citing Use of MedChemExpress (MCE) RapaLink-1
More- Cell. 2025 Jun 12;188(12):3219-3237.e18. [Abstract]
- Mol Cell. 2025 Sep 18;85(18):3486-3504.e7. [Abstract]
- Nat Commun. 2025 Oct 20;16(1):9250. [Abstract]
- Nat Commun. 2024 Jul 19;15(1):6076. [Abstract]
- Sci Signal. 2025 Sep 2;18(902):eadw3231. [Abstract]
- Nutrients. 2022 Jul 22;14(15):3022. [Abstract]
- Int J Mol Sci. 2023 Jan 20;24(3):2055. [Abstract]
- iScience. 2022 Oct 28;25(11):105458. [Abstract]
- SLAS Technol. 2023 Aug;28(4):223-229. [Abstract]
- bioRxiv. 2026 May 2.
- bioRxiv. 2025 Sep 11.
- bioRxiv. 2025 May 23:2025.05.20.655155. [Abstract]
- University of Washington. 2024.
- bioRxiv. 2023 Aug 4:2023.08.04.552011. [Abstract]
Customer Validation & Images
-
RT-PCR
-
WB
-
Cell Proliferation/Viability Assay
-
Apoptosis Analysis
Biological Activity
|
mTOR |
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.
-
Cell Line:U87MG cells
-
Concentration:0-200 nM
-
Incubation Time:3 days
-
Result:Showed growth inhibition.
-
Cell Line:U87MG cells
-
Concentration:0-12.5 nM
-
Incubation Time:48 hours
-
Result:Arrested cells at G0/G1.
-
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.
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.
Chemical Information
-
CAS No. 1887095-82-0
-
Appearance Solid
-
Molecular Weight 1784.14
-
Formula C91H138N12O24
-
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)
Publications (14)
-
Journal Impact Factor
-
Most Recent
-
Cell
2025 Jun 12;188(12):3219-3237.e18. PMID: 40250420 -
Mol Cell
mTOR inhibition reprograms cellular lipid homeostasis by inducing alternative lipid uptake and promoting cholesterol transport. [Abstract]2025 Sep 18;85(18):3486-3504.e7. PMID: 40972529 -
Nat Commun
Mitochondrial one-carbon metabolism is required for TGF-β-induced glycine synthesis and fibrotic responses. [Abstract]2025 Oct 20;16(1):9250. PMID: 41115888
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).
-
Nat Commun
Combined inhibition of KRASG12C and mTORC1 kinase is synergistic in non-small cell lung cancer. [Abstract]2024 Jul 19;15(1):6076. PMID: 39025835
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.
-
Sci Signal
MAPK and mTORC1 signaling converge to drive cyclin D1 protein production to enable cell cycle reentry in melanoma persister cells. [Abstract]2025 Sep 2;18(902):eadw3231. PMID: 40892895 -
Nutrients
mTORC1 and mTORC2 Complexes Regulate the Untargeted Metabolomics and Amino Acid Metabolites Profile through Mitochondrial Bioenergetic Functions in Pancreatic Beta Cells. [Abstract]2022 Jul 22;14(15):3022. PMID: 35893876 -
Int J Mol Sci
2023 Jan 20;24(3):2055. PMID: 36768380
RapaLink-1 purchased from MedChemExpress. Usage Cited in: Int J Mol Sci. 2023 Jan 20;24(3):2055. [Abstract]
Rapalink-1 (10 nM) alone and in combination with CR-1-B-R1 or Zotatifin increased apoptosis in the two cell lines.
-
iScience
Reciprocal effects of mTOR inhibitors on pro-survival proteins dictate therapeutic responses in tuberous sclerosis complex. [Abstract]2022 Oct 28;25(11):105458. PMID: 36388985 -
SLAS Technol
In Vitro Delivery of mTOR inhibitors by Kidney-Targeted Micelles for Autosomal Dominant Polycystic Kidney Disease. [Abstract]2023 Aug;28(4):223-229. PMID: 36804177 -
-
-
bioRxiv
Dissociation of the mTOR protein interaction network following neuronal activation is altered by Shank3 mutation. [Abstract]2025 May 23:2025.05.20.655155. PMID: 40475644 -
-
bioRxiv
2023 Aug 4:2023.08.04.552011. PMID: 37577705
Solvent & Solubility
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.
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.
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.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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.
Please enter the basic information of animal experiments:
-
-
-
-
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
-
%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
-
%+
-
+%Tween-80 + +
-
%Saline +
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).
Working solution concentration: 0.22 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)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
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
-
Data Sheet (283 KB)
-
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
-
Handling Instructions (2659 KB)
References
[1]. Fan Q, et al. A Kinase Inhibitor Targeted to mTORC1 Drives Regression in Glioblastoma. Cancer Cell. 2017 Mar 13;31(3):424-435. [Content Brief]
[2]. Kuroshima K, et al. Potential new therapy of Rapalink-1, a new generation mammalian target of rapamycin inhibitor, against SU 11248-resistant renal cell carcinoma. Cancer Sci. 2020 May;111(5):1607-1618. [Content Brief]
[3]. Rodrik-Outmezguine VS, et al. Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor. Nature. 2016 Jun 9;534(7606):272-6. [Content Brief]
[4]. Mu F, et al. RapaLink-1 plays an antithrombotic role in antiphospholipid syndrome by improving autophagy both in vivo and vitro. Biochem Biophys Res Commun. 2020 Apr 30;525(2):384-391. [Content Brief]
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 |
RapaLink-1 Related Classifications
HY-111373 Related Classifications
Powered by Bioz