Synonyms: 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
Comment: RapaLink-1 is a new-generation bivalent (bitopic) mTOR inhibitor, comprising a rapamycin-FRB-binding element ( sirolimus, a.k.a. rapamycin) linked to an ATP binding site competitive TORKi ( sapanisertib, a.k.a. MLN0128) via a PEG linker [ 1]. RapaLink-1 is able to overcome resistance to TORKis of mutant mTOR proteins in vitro, inhibiting proliferation MCF-7 cells at levels comparable to rapamycin or a combination of rapamycin and MLN0128.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors
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33
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Hydrogen bond donors
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5
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Rotatable bonds
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46
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Topological polar surface area
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448.98
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Molecular weight
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1782.99
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XLogP
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3.64
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No. Lipinski's rules broken
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2
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SMILES / InChI / InChIKey
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Canonical SMILES
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COC1CC(CCC1OCCOCc1nnn(c1)CCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)NCCCCn1nc(c2c1ncnc2N)c1ccc2c(c1)nc(o2)N)CC(C1CC(=O)C(C)C=C(C)C(O)C(OC)C(=O)C(C)CC(C)C=CC=CC=C(C(CC2OC(C(=O)C(=O)N3C(C(=O)O1)CCCC3)(O)C(C)CC2)OC)C)C
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Isomeric SMILES
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CO[C@@H]1C[C@H](CC[C@@H]1OCCOCc1nnn(c1)CCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)NCCCCn1nc(c2c1ncnc2N)c1ccc2c(c1)nc(o2)N)C[C@H]([C@@H]1CC(=O)[C@H](C)/C=C(\C)/[C@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)/C=C/C=C/C=C(/[C@@H](C[C@H]2O[C@](C(=O)C(=O)N3[C@@H](C(=O)O1)CCCC3)(O)[C@H](C)CC2)OC)\C)C
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InChI
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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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InChI Key
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QDOGZMBPRITPMZ-LFEDRMHTSA-N
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