Details
Stereochemistry | ACHIRAL |
Molecular Formula | C21H22N6O3 |
Molecular Weight | 406.4378 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC=CC2=C1NC(=C2)C3=C4N(N=CN=C4N)C(=N3)[C@H]5CC[C@@H](CC5)C(O)=O
InChI
InChIKey=JROFGZPOBKIAEW-HAQNSBGRSA-N
InChI=1S/C21H22N6O3/c1-30-15-4-2-3-13-9-14(25-16(13)15)17-18-19(22)23-10-24-27(18)20(26-17)11-5-7-12(8-6-11)21(28)29/h2-4,9-12,25H,5-8H2,1H3,(H,28,29)(H2,22,23,24)/t11-,12-
Molecular Formula | C21H22N6O3 |
Molecular Weight | 406.4378 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
OSI-027 is an orally bioavailable mammalian inhibitor of mTOR kinase and has antineoplastic activity. OSI-027 binds to and inhibits of the catalytic site of mTOR, which is a central part of two protein complexes, mTORC1 and mTORC2, which may result in tumor cell apoptosis and a decrease in tumor cell proliferation. OSI-027 is in phase I clinical trial for the investigation on patients with advanced solid tumors or lymphoma.
Originator
Sources: http://google.com/patents/US20070112005
Curator's Comment: Chen X, Coate H, Crew AP, Dong H-Q, Honda A, Mulvihill MJ, et al. Fused bicyclic mTOR inhibitors. US-20070112005 (OSI Pharmaceuticals Inc).
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2221341 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21673091 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
11007 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27002938 |
160 mg 1 times / day multiple, oral dose: 160 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
OSI-027 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
8780 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27002938 |
240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered: |
OSI-027 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
9329 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27002938 |
160 mg 1 times / day single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered: |
OSI-027 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1110 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27002938 |
50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
OSI-027 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3040 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27002938 |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
OSI-027 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
105663 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27002938 |
160 mg 1 times / day multiple, oral dose: 160 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
OSI-027 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
125278 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27002938 |
240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered: |
OSI-027 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
131223 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27002938 |
160 mg 1 times / day single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered: |
OSI-027 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
17246 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27002938 |
50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
OSI-027 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
46250 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27002938 |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
OSI-027 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
11.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27002938 |
160 mg 1 times / day multiple, oral dose: 160 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
OSI-027 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
13.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27002938 |
240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered: |
OSI-027 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
10.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27002938 |
160 mg 1 times / day single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered: |
OSI-027 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
10.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27002938 |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
OSI-027 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
PubMed
Title | Date | PubMed |
---|---|---|
Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin. | 2011 Aug |
|
Discovery of 9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one (Torin2) as a potent, selective, and orally available mammalian target of rapamycin (mTOR) inhibitor for treatment of cancer. | 2011 Mar 10 |
|
The Antipancreatic Cancer Activity of OSI-027, a Potent and Selective Inhibitor of mTORC1 and mTORC2. | 2015 Oct |
|
OSI-027 inhibits pancreatic ductal adenocarcinoma cell proliferation and enhances the therapeutic effect of gemcitabine both in vitro and in vivo. | 2015 Sep 22 |
|
A first in man, dose-finding study of the mTORC1/mTORC2 inhibitor OSI-027 in patients with advanced solid malignancies. | 2016 Apr 12 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27002938
30 mg per day, once daily
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26213847
OSI-027 downregulated multidrug resistance (MDR)-1, which has been implicated in chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC) cells and enhanced apoptosis induced by gemcitabine in the three PDAC cell lines. Human PDAC cell lines (Panc-1, BxPC-3, CFPAC-1) were plated at a density of 3000 cells per well in 96-well plates and the media was removed and replaced by serum free media. 24 hours later the serum free media was replaced by complete media with the addition of OSI-027 at concentration 1.25, 2.5, 5, 10, 20, 40, and 80 μM for at 24, 48, and 72 hours.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 02:19:02 GMT 2023
by
admin
on
Sat Dec 16 02:19:02 GMT 2023
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Record UNII |
25MKH1SZ0M
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Record Status |
Validated (UNII)
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Record Version |
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FDA ORPHAN DRUG |
759820
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