
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)






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 |
![]() ![]() |
1G | Get Quote | In Stock |
![]() ![]() |
Biological Information
-
Product NameOSI-027
-
NoteResearch use only, not for human use.
-
Brief DescriptionA potent and selective inhibitor of mTORC1 and mTORC2 with IC50 of 22 nM and 65 nM, respectively.
-
DescriptionA 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 VitroOSI-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 VivoEffects 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.
-
SynonymsOSI027 | OSI 027
-
PathwayPI3K/Akt/mTOR signaling
-
TargetmTOR
-
RecptorDNA-PK| mTOR| mTORC1| mTORC2| PI3Kγ
-
Research AreaCancer
-
IndicationBlood cancer
Chemical Information
-
CAS Number936890-98-1
-
Formula Weight406.4378
-
Molecular FormulaC21H22N6O3
-
Purity>98% (HPLC)
-
Solubility10 mM in DMSO
-
SMILESCOC1=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 NameCyclohexanecarboxylic 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℃)
-
ShippingWith 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.
molnova catalog



related products
-
Zotarolimus
Zotarolimus (ABT-578, A 179578) is a semi-synthetic analogue of rapamycin, inhibits FKBP-12.
-
MHY-1685
MHY-1685 is a mammalian target of rapamycin (mTOR) inhibitor and a senescence inhibitor that can rejuvenate senile hCSCs by modulating autophagy.
-
Rheb inhibitor NR1
Rheb inhibitor NR1 is a selective mTORC1 inhibitor that suppresses the phosphorylation of T389pS6K1 and enhances the phosphorylation of S473pAKT.