OSI-027 free base · Synonyms: ASP7486
OSI-027 is a potent, selective, orally active and ATP-competitive mTOR kinase activity inhibitor.
For research use only. Not for human or veterinary use.
OSI-027 structure
CAS No.: 936890-98-1
Pack sizes & pricing
| Size | Price | SKU | Stock | |
|---|---|---|---|---|
| 250 mg | USD 485.00 | BP-02110-250mg | In stock | Get quote |
| 500 mg | USD 785.00 | BP-02110-500mg | In stock | Get quote |
| 1 g | USD 1,185.00 | BP-02110-1g | In stock | Get quote |
| 5 g | Inquire | BP-02110-5g | Inquire | Inquire |
Need another size or custom synthesis? Request a quote.
Description
OSI-027 (ASP7486) is a potent, selective, orally active and ATP-competitive mTOR kinase activity inhibitor with an IC50 of 4 nM. OSI-027 targets both mTORC1 and mTORC2 with IC50s of 22 nM and 65 nM, respectively.
Biological activity
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.
Identifiers
- SMILES
-
COC1=CC=CC2=C1NC(=C2)C1=C2N(N=CN=C2N)C(=N1)[C@H]1CC[C@@H](CC1)C(O)=O - InChIKey
-
JROFGZPOBKIAEW-HAQNSBGRSA-N
Specifications
- MW (average)
- 406.4378
- Formula
- C21H22N6O3
- CAS No.
- 936890-98-1
- Physical state
- Solid
- Color
- light yellow to yellow
- Shipping
- Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
- Storage
- Powder -20℃ 2 years; In solvent -20℃ 1 month;
Solubility
Soluble in DMSO