Basic information Safety Supplier Related

Wortmannin-Rapamycin Conjugate

Basic information Safety Supplier Related

Wortmannin-Rapamycin Conjugate Basic information

Product Name:
Wortmannin-Rapamycin Conjugate
Synonyms:
  • Wortmannin-Rapamycin Conjugate
  • ATASUAOFUAOSAN-NVEIXTJJSA-N
  • Rapamycin, 42-[8-[(1E,4S,4aR,5R,6aS,7S,9aR)-5-(acetyloxy)-1-[[[3-(dimethylamino)propyl]methylamino]methylene]-1,2,4,4a,5,6,6a,7,8,9,9a,10-dodecahydro-11-hydroxy-4-(methoxymethyl)-4a,6a-dimethyl-2,10-dioxocyclopenta[5,6]naphtho[1,2-c]pyran-7-yl] octanedioate]
CAS:
1067892-47-0
MF:
C88H131N3O23
MW:
1598.99
Mol File:
1067892-47-0.mol
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Wortmannin-Rapamycin Conjugate Chemical Properties

storage temp. 
Store at -20°C
solubility 
DMF: 30 mg/ml; DMSO: 20 mg/ml; Ethanol: 5 mg/ml
form 
A crystalline solid
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Wortmannin-Rapamycin Conjugate Usage And Synthesis

Description

Phosphoinositide 3-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-rapamycin conjugate consists of analogs of 17-hydroxy wortmannin and rapamycin conjugated via a prodrug linker. Hydrolysis of the prodrug linker in vivo releases the inhibitors. The wortmannin-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-blocker bevacizumab, produces substantial regression of larger A498 tumors. Finally, the wortmannin-rapamycin conjugate is tolerated better than an equivalent mixture of the inhibitors.

Uses

Wortmannin-Rapamycin Conjugate 1 (compound 7c) is a furan ring-opened derivative of wortmannin-rapamycin conjugate with potent antitumor activities and a fine water solubility. Wortmannin-Rapamycin Conjugate 1 can inhibit the AKT phosphorylation in the tumor and can be used for cancer research[1].

in vivo

Wortmannin-Rapamycin Conjugate 1 (3,5 mg/kg, i.v., weekly for 13 d) exerts significant antitumor activity on U87MG mouse xenogrgaft model[1].
Wortmannin-Rapamycin Conjugate 1 (15 mg/kg, i.v., 2 h) significantly inhibits the AKT phosphorylation in the tumor of U87MG mouse xenogrgaft model[1].
Wortmannin-Rapamycin Conjugate 1 (15 mg/kg, i.v., weekly for 20 d ) completely inhibits the growth of HT29 colon tumor, a non-sensitive colon tumor model to rapamycin or wortmannin analogues in tumor-bearing mice[1].
Wortmannin-Rapamycin Conjugate 1 (30 mg/kg, i.v., weekly for 38 d ) exerts a substantial regression of larger A498 tumors with 200 μg Bevacizumab (HY-P9906) in A498 tumor-bearing mice[1].

Animal Model:HT29 bearing nude mice[1]
Dosage:15 mg/kg, weekly for 20 d
Administration:Intravenous injection (i.v.)
Result:Showed no significant growth in tumor volume while an equivalent physical mixture of the Rapamycin and Wortmannin derivative was poorly tolerated.

References

[1] Ayral-Kaloustian S, et al. Hybrid inhibitors of phosphatidylinositol 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR): design, synthesis, and superior antitumor activity of novel wortmannin-rapamycin conjugates. J Med Chem. 2010 Jan 14;53(1):452-9. DOI:10.1021/jm901427g

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