OSI-027

CAS No. 936890-98-1

OSI-027( OSI027 | OSI 027 )

Catalog No. M16711 CAS No. 936890-98-1

A potent and selective inhibitor of mTORC1 and mTORC2 with IC50 of 22 nM and 65 nM, respectively.

Purity : >98% (HPLC)

COA Datasheet HNMR HPLC MSDS Handing Instructions
Size Price / USD Stock Quantity
2MG 43 In Stock
5MG 70 In Stock
10MG 127 In Stock
25MG 235 In Stock
50MG 368 In Stock
100MG 536 In Stock
200MG Get Quote In Stock
500MG Get Quote In Stock
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Biological Information

  • Product Name
    OSI-027
  • Note
    Research use only, not for human use.
  • Brief Description
    A potent and selective inhibitor of mTORC1 and mTORC2 with IC50 of 22 nM and 65 nM, respectively.
  • Description
    A potent and selective inhibitor of mTORC1 and mTORC2 with IC50 of 22 nM and 65 nM, respectively; displays >100-fold selectivity for mTOR over PI3Kα, PI3Kβ, PI3Kγ, and DNA-PK; inhibits phosphorylation of the mTORC1 substrates 4E-BP1 and S6K1 as well as the mTORC2 substrate AKT in diverse cancer models in vitro and in vivo; demonstrates robust antitumor activity in human xenograft models.Blood Cancer Phase 1 Discontinued(In Vitro):OSI-027 is an ATP-competitive inhibitor, which targets both mTORC1 and mTORC2 with IC50s of 22 nM and 65 nM. OSI-027 also inhibits PI3K-α, PI3K-γ and DNA-PK with IC50s of 1.3 μM, 0.42 μM and 1.0 μM. OSI-027 inhibits mTOR signaling of phospho-4E-BP1 with an IC50 of 1 μM.(In Vivo):Effects on GEO colorectal xenograft growth treated with Rapamycin or OSI-027 for 12 days are consistent with our in vitro experiments. Treatment with Rapamycin (20 mg/kg) inhibits phospho-S6 and phospho-4E-BP1, while Akt phosphorylation is increased by 29%. In contrast, OSI-027 (65 mg/kg) inhibits both mTORC1 and mTORC2 effectors. After 2 hours, decreased 4E-BP1, Akt, and S6 phosphorylation is observed and inhibition of S6 and Akt is sustained for 24 hours. The plasma drug concentration of OSI-027 inversely correlated with these effects on mTORC1 and mTORC2 signaling. The median plasma drug concentration with OSI-027 is 21.3 μM at 2 hours and 14.9 μM at 8 hours. The in vivo efficacy of OSI-027 plus Sunitinib is tested in H292 human lung and Ovcar-5 human ovarian xenograft tumors. H292 tumors, treated with OSI-027 (50 mg/kg) for 21 days have 61% median tumor growth inhibition for the duration of treatment (TGI). Sunitinib (40 mg/kg) for 21 days had 47% median TGI. Combining OSI-027 with Sunitinib, however, has a median TGI of 100% with 59% maximal tumor regression, a statistically significant improvement over either agent alone. Ovcar-5 xenograft tumors treated with OSI-027 or Sunitinib have a 55% and 68% median TGI, respectively. OSI-027 administered with Sunitinib has a significantly better median TGI of 100% with 38% maximal tumor regression.In the Rapamycin (RAPA) group, three rats exhibit symptoms typical of LTx-aGVHD and die 27 to 35 days after liver transplantation (LT); the remaining five rats do not develop LTx-aGVHD symptoms and survive for more than 100 days. In contrast, seven rats in the OSI-027 group survive for more than 100 days without symptoms of LTx-aGVHD, and only one rat exhibits LTx-aGVHD symptoms and dies on day 33 after LT.
  • In Vitro
    OSI-027 is an ATP-competitive inhibitor, which targets both mTORC1 and mTORC2 with IC50s of 22 nM and 65 nM. OSI-027 also inhibits PI3K-α, PI3K-γ and DNA-PK with IC50s of 1.3 μM, 0.42 μM and 1.0 μM. OSI-027 inhibits mTOR signaling of phospho-4E-BP1 with an IC50 of 1 μM.
  • In Vivo
    Effects on GEO colorectal xenograft growth treated with Rapamycin or OSI-027 for 12 days are consistent with our in vitro experiments. Treatment with Rapamycin (20 mg/kg) inhibits phospho-S6 and phospho-4E-BP1, while Akt phosphorylation is increased by 29%. In contrast, OSI-027 (65 mg/kg) inhibits both mTORC1 and mTORC2 effectors. After 2 hours, decreased 4E-BP1, Akt, and S6 phosphorylation is observed and inhibition of S6 and Akt is sustained for 24 hours. The plasma drug concentration of OSI-027 inversely correlated with these effects on mTORC1 and mTORC2 signaling. The median plasma drug concentration with OSI-027 is 21.3 μM at 2 hours and 14.9 μM at 8 hours. The in vivo efficacy of OSI-027 plus Sunitinib is tested in H292 human lung and Ovcar-5 human ovarian xenograft tumors. H292 tumors, treated with OSI-027 (50 mg/kg) for 21 days have 61% median tumor growth inhibition for the duration of treatment (TGI). Sunitinib (40 mg/kg) for 21 days had 47% median TGI. Combining OSI-027 with Sunitinib, however, has a median TGI of 100% with 59% maximal tumor regression, a statistically significant improvement over either agent alone. Ovcar-5 xenograft tumors treated with OSI-027 or Sunitinib have a 55% and 68% median TGI, respectively. OSI-027 administered with Sunitinib has a significantly better median TGI of 100% with 38% maximal tumor regression.In the Rapamycin (RAPA) group, three rats exhibit symptoms typical of LTx-aGVHD and die 27 to 35 days after liver transplantation (LT); the remaining five rats do not develop LTx-aGVHD symptoms and survive for more than 100 days. In contrast, seven rats in the OSI-027 group survive for more than 100 days without symptoms of LTx-aGVHD, and only one rat exhibits LTx-aGVHD symptoms and dies on day 33 after LT.
  • Synonyms
    OSI027 | OSI 027
  • Pathway
    PI3K/Akt/mTOR signaling
  • Target
    mTOR
  • Recptor
    DNA-PK| mTOR| mTORC1| mTORC2| PI3Kγ
  • Research Area
    Cancer
  • Indication
    Blood cancer

Chemical Information

  • CAS Number
    936890-98-1
  • Formula Weight
    406.4378
  • Molecular Formula
    C21H22N6O3
  • Purity
    >98% (HPLC)
  • Solubility
    10 mM in DMSO
  • SMILES
    COC1=CC=CC2=C1NC(=C2)C1=C2N(N=CN=C2N)C(=N1)[C@H]1CC[C@@H](CC1)C(O)=O |r,c:4,6,10,16,18,22,t:2,13|
  • Chemical Name
    Cyclohexanecarboxylic acid, 4-[4-amino-5-(7-methoxy-1H-indol-2-yl)imidazo[5,1-f][1,2,4]triazin-7-yl]-, trans-

Shipping & Storage Information

  • Storage
    (-20℃)
  • Shipping
    With Ice Pack
  • Stability
    ≥ 2 years

Reference

1. Carayol N, et al. Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12469-74. 2. Falcon BL, et al. Cancer Res. 2011 Mar 1;71(5):1573-83. 3. Altman JK, et al. Clin Cancer Res. 2011 Jul 1;17(13):4378-88. 4. Bhagwat SV, et al. Mol Cancer Ther. 2011 Aug;10(8):1394-406.
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