Synonym
OXA-01; OXA01; OXA 01.
IUPAC/Chemical Name
trans-4-[8-amino-1-(7-chloro-1H-indol-2-yl)imidazo[1,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid
InChi Key
UXCAKZGNKOZXBM-HAQNSBGRSA-N
InChi Code
InChI=1S/C21H20ClN5O2/c22-14-3-1-2-13-10-15(25-16(13)14)17-18-19(23)24-8-9-27(18)20(26-17)11-4-6-12(7-5-11)21(28)29/h1-3,8-12,25H,4-7H2,(H2,23,24)(H,28,29)/t11-,12-
SMILES Code
O=C([C@H]1CC[C@H](C2=NC(C(N3)=CC4=C3C(Cl)=CC=C4)=C5C(N)=NC=CN52)CC1)O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
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 Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
OXA-01 is a potent mTORC1 and mTORC2 inhibitor, with IC50 values of 29 nM and 7 nM.
In vitro activity:
Effects of OXA-01, OSI-027, and rapamycin on mTORC1 and mTORC2 signaling were compared in vitro. OXA-01 or OSI-027, but not rapamycin, dose-dependently attenuated Akt phosphorylation at the mTORC2-specific Ser473 site and the downstream substrate of Akt, PRAS40 (Supplemental Figure 1A). OXA-01 and OSI-027 inhibited 4E-BP1 phosphorylation at Ser37/46, which are typically rapamycin insensitive.
Reference: Cancer Res. 2011 Mar 1;71(5):1573-83. https://pubmed.ncbi.nlm.nih.gov/21363918/
In vivo activity:
Consistent with their inhibition of mTORC1 and mTORC2, both OSI-027 (Figure 2C) and OXA-01 (Figure 2D) slowed tumor growth more than did rapamycin. As indicated by reduced tumor growth in mouse xenograft models, OXA-01 treatment decreased cellular proliferation determined by phospho-histone H3 (Figure 3C) and increased apoptosis measured by activated-caspase-3 (Figure 3D).
Reference: Cancer Res. 2011 Mar 1;71(5):1573-83. https://pubmed.ncbi.nlm.nih.gov/21363918/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
1.0 |
2.44 |
| DMSO |
3.0 |
7.32 |
| DMSO:PBS (pH 7.2) (1:3) |
0.3 |
0.61 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
409.87
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
Falcon BL, Barr S, Gokhale PC, Chou J, Fogarty J, Depeille P, Miglarese M, Epstein DM, McDonald DM. Reduced VEGF production, angiogenesis, and vascular regrowth contribute to the antitumor properties of dual mTORC1/mTORC2 inhibitors. Cancer Res. 2011 Mar 1;71(5):1573-83. doi: 10.1158/0008-5472.CAN-10-3126. PMID: 21363918; PMCID: PMC3077087.
In vitro protocol:
Falcon BL, Barr S, Gokhale PC, Chou J, Fogarty J, Depeille P, Miglarese M, Epstein DM, McDonald DM. Reduced VEGF production, angiogenesis, and vascular regrowth contribute to the antitumor properties of dual mTORC1/mTORC2 inhibitors. Cancer Res. 2011 Mar 1;71(5):1573-83. doi: 10.1158/0008-5472.CAN-10-3126. PMID: 21363918; PMCID: PMC3077087.
In vivo protocol:
Falcon BL, Barr S, Gokhale PC, Chou J, Fogarty J, Depeille P, Miglarese M, Epstein DM, McDonald DM. Reduced VEGF production, angiogenesis, and vascular regrowth contribute to the antitumor properties of dual mTORC1/mTORC2 inhibitors. Cancer Res. 2011 Mar 1;71(5):1573-83. doi: 10.1158/0008-5472.CAN-10-3126. PMID: 21363918; PMCID: PMC3077087.
1: Bhagwat SV, Gokhale PC, Crew AP, Cooke A, Yao Y, Mantis C, Kahler J, Workman
J, Bittner M, Dudkin L, Epstein DM, Gibson NW, Wild R, Arnold LD, Houghton PJ,
Pachter JA. Preclinical characterization of OSI-027, a potent and selective
inhibitor of mTORC1 and mTORC2: distinct from rapamycin. Mol Cancer Ther. 2011
Aug;10(8):1394-406. doi: 10.1158/1535-7163.MCT-10-1099. PubMed PMID: 21673091.
2: Falcon BL, Barr S, Gokhale PC, Chou J, Fogarty J, Depeille P, Miglarese M,
Epstein DM, McDonald DM. Reduced VEGF production, angiogenesis, and vascular
regrowth contribute to the antitumor properties of dual mTORC1/mTORC2 inhibitors.
Cancer Res. 2011 Mar 1;71(5):1573-83. doi: 10.1158/0008-5472.CAN-10-3126. PubMed
PMID: 21363918; PubMed Central PMCID: PMC3077087.
3: Manyahi J, Moyo SJ, Kibwana U, Goodman RN, Allman E, Hubbard ATM, Blomberg B, Langeland N, Roberts AP. First identification of blaNDM-5 producing Escherichia coli from neonates and a HIV infected adult in Tanzania. J Med Microbiol. 2022 Feb;71(2):001513. doi: 10.1099/jmm.0.001513. PMID: 35225760; PMCID: PMC8941953.
