1887095-82-0
1887095-82-0 structure
- Name: RapaLink-1
- Chemical Name: RapaLink-1
- CAS Number: 1887095-82-0
- Molecular Formula: C91H138N12O24
- Molecular Weight: 1798.162
- Catalog: Signaling Pathways Autophagy Autophagy
- Create Date: 2018-06-18 18:35:30
- Modify Date: 2024-01-10 18:13:23
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RapaLink-1, the third-generation bivalent mTOR inhibitor, combines Rapamycin with MLN0128 (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. Anticancer activity[1][2].
| Name | RapaLink-1 |
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| Description | RapaLink-1, the third-generation bivalent mTOR inhibitor, combines Rapamycin with MLN0128 (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. Anticancer activity[1][2]. |
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| Related Catalog | |
| 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 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]. 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]. 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. |
| References |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Molecular Formula | C91H138N12O24 |
| Molecular Weight | 1798.162 |
| Exact Mass | 1797.010376 |
| LogP | 1.85 |
| Index of Refraction | 1.592 |