RapaLink-1 - ≥98% , CAS No.1887095-82-0

CAS: 1887095-82-0 Cat. No.: R650876 Formula: C₉₁H₁₃₈N₁₂O₂₄ Molecular Weight: 1784.1 PubChem CID: 145708103

GRADE & PURITY ≥98%

Storage

Store at 2-8°C,Desiccated

Shipped In

Wet ice

Overview

RapaLink-1, the third-generation bivalent mTOR inhibitor, combines Rapamycin with MLN0128 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

In Vitro

RapaLink-1 (0-200 nM; 3 days) shows U87MG cells growth inhibition. RapaLink-1 (0-12.5 nM; 48 hours) arrests U87MG cells at G0/G1. RapaLink-1 selectively inhibits p-RPS6 S235/236 and p-4EBP1 T37/46 at doses as low as 1.56 nM. Rapalink-1 (100 nM; 24 to 96 hours) suppressed renal cell carcinoma (RCC) cell proliferation by inducing apoptosis and cell cycle arrest. 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Proliferation AssayCell Line: U87MG cells Concentration: 0-200 nM Incubation Time: 3 days Result: Showed growth inhibition. Cell Cycle AnalysisCell Line: U87MG cells Concentration: 0-12.5 nM Incubation Time: 48 hours Result: Arrested cells at G0/G1. Western Blot AnalysisCell Line: U87MG cells Concentration: 0.39-12.5 nM Incubation Time: 3 hours Result: Selectively inhibited p-RPS6 S235/236 and p-4EBP1 T37/46 at doses as low as 1.56 nM. The mTORC2 targets p-AKT S473 , p-SGK1 S78 , and p-NDRG1 T346 , and the p-AKT S473 target p-GSK3β S9 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 . 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 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.

Form:Solid

IC50& Target:mTOR

Specifications

Specifications & Purity

≥98%

Biochemical and Physiological Mechanisms

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 inhibi

Storage

Store at 2-8°C,Desiccated

Shipped In

Wet ice

This product requires cold chain shipping. Ground and other economy services are not available.

Purity

≥98%

Names and Identifiers

Canonical Smiles

CC1CCC2CC(C(=CC=CC=CC(CC(C(=O)C(C(C(=CC(C(=O)CC(OC(=O)C3CCCCN3C(=O)C(=O)C1(O2)O)C(C)CC4CCC(C(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

IUPAC 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-[(1S,2R,4R)-4-[(2R)-2-[(1R,9R,12S,15R,16Z,18S,21R,23S,24Z,26Z,28Z,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

InChIKey

QDOGZMBPRITPMZ-IJSXHDAKSA-N

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

PubChem CID

145708103

MeSH Entry Terms

40-O-(2-((1-(32-(4-amino-3-(2-aminobenzo(d)oxazol-5-yl)-1H-pyrazolo(3,4-d)pyrimidin-1-yl)-27-oxo-3,6,9,12,15,18,21,24-octaoxa-28-azadotriacontyl)-1H-1,2,3-triazol-4-yl)methoxy)ethyl)-rapamycin;RapaLink-1

Molecular Weight

1784.1

Chemical and Physical Properties

• Solubility: DMSO : 178 mg/mL (99.77 mM; Need ultrasonic and warming) H2O : <0.1 mg/mL (insoluble)