Wortmannin-Rapamycin Conjugate

• CAT Number: R064532
• CAS Number: 1067892-47-0
• Molecular Formula: C88H131N3O23
• Molecular Weight: 1598.9
• Purity: ≥95%
• Synonyms: 1-(4S,4aR,5R,6aS,7S,9aR,E)-1-(((3-(dimethylamino)propyl)(methyl)amino)methylene)-7,11-dihydroxy-4-(methoxymethyl)-4a,6a-dimethyl-2,10-dioxo-1,2,4,4a,5,6,6a,7,8,9,9a,10-dodecahydroindeno[4,5-h]isochromen-5-yl acetate 8-(7E,15E,17E,19E)-9,10,12,13,14,2
• Target: Akt
• Storage: -20°C
• InChI: InChI=1S/C88H131N3O23/c1-51-28-21-20-22-29-52(2)66(106-15)46-60-35-33-57(7)88(104,114-60)82(100)83(101)91-41-26-25-30-63(91)85(103)111-67(47-64(93)53(3)43-56(6)78(97)81(108-17)77(96)55(5)42-51)54(4)44-59-34-37-65(68(45-59)107-16)110-72(94)31-23-18-19
• InChIKey: GVMCLKAVNVFURS-UXLLMVCWSA-N
• SMILES: O=C(O[C@H]1[C@H](OC)C[C@H](C[C@@H](C)[C@@](CC([C@H](C)/C=C(C)/[C@@H](O)[C@@H](OC)C([C@H](C)C[C@H](C)/C=C/C=C/C=C(C)/[C@@H](OC)C[C@](O2)([H])CC[C@@H](C)[C@]2(O)C3=O)=O)=O)([H])OC([C@]4([H])CCCCN4C3=O)=O)CC1)CCCCCCC(O[C@H]5CC[C@]6([H])[C@]5(C)C[C@@H](O

Phosphoinositide 3-<wbr></wbr>kinase (PI3K) and mammalian target of rapamycin (mTOR) act synergistically in promoting cancer. Wortmannin is a potent inhibitor of PI3K enzymes, while rapamycin blocks mTOR Complex 1 TORC1. Wortmannin-<wbr></wbr>rapamycin conjugate consists of analogs of 17-<wbr></wbr>hydroxy wortmannin and rapamycin conjugated via a prodrug linker. Hydrolysis of the prodrug linker in vivo releases the inhibitors. The wortmannin-<wbr></wbr>rapamycin conjugate inhibits the growth of HT-29 colon tumors and A498 renal tumors in mice better than rapamycin alone. Also, the conjugate, when given in combination with the VEGF-<wbr></wbr>blocker bevacizumab, produces substantial regression of larger A498 tumors. Finally, the wortmannin-<wbr></wbr>rapamycin conjugate is tolerated better than an equivalent mixture of the inhibitors.

Reference

1.Fruman, D.A.,Meyers, R.E., and Cantley, L.C. Phosphoinositide kinases. Annual Reviews of Biochemistry 67, 481-507 (2008).