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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
Structure of OSI-027

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-

HIDE SMILES / InChI

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

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

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
11007 ng/mL
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
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
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
105663 ng × h/mL
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
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
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
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
11.9 h
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
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
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
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

PubMed

TitleDatePubMed
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
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

30 mg per day, once daily
Route of Administration: Oral
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 Sat Dec 16 02:19:02 GMT 2023
Edited
by admin
on Sat Dec 16 02:19:02 GMT 2023
Record UNII
25MKH1SZ0M
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
OSI-027
Code English
CYCLOHEXANECARBOXYLIC ACID, 4-(4-AMINO-5-(7-METHOXY-1H-INDOL-2-YL)IMIDAZO(5,1-F)(1,2,4)TRIAZIN-7-YL)-, TRANS-
Common Name English
ASP7486
Code English
ASP-7486
Code English
CERC-006
Code English
AEVI-006
Code English
OSI027
Code English
CERC006
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 759820
Created by admin on Sat Dec 16 02:19:02 GMT 2023 , Edited by admin on Sat Dec 16 02:19:02 GMT 2023
Code System Code Type Description
FDA UNII
25MKH1SZ0M
Created by admin on Sat Dec 16 02:19:02 GMT 2023 , Edited by admin on Sat Dec 16 02:19:02 GMT 2023
PRIMARY
CAS
936890-98-1
Created by admin on Sat Dec 16 02:19:02 GMT 2023 , Edited by admin on Sat Dec 16 02:19:02 GMT 2023
PRIMARY
EPA CompTox
DTXSID901025951
Created by admin on Sat Dec 16 02:19:02 GMT 2023 , Edited by admin on Sat Dec 16 02:19:02 GMT 2023
PRIMARY
ChEMBL
CHEMBL3120215
Created by admin on Sat Dec 16 02:19:02 GMT 2023 , Edited by admin on Sat Dec 16 02:19:02 GMT 2023
PRIMARY
DRUG BANK
DB12387
Created by admin on Sat Dec 16 02:19:02 GMT 2023 , Edited by admin on Sat Dec 16 02:19:02 GMT 2023
PRIMARY
NCI_THESAURUS
C78476
Created by admin on Sat Dec 16 02:19:02 GMT 2023 , Edited by admin on Sat Dec 16 02:19:02 GMT 2023
PRIMARY
SMS_ID
100000175311
Created by admin on Sat Dec 16 02:19:02 GMT 2023 , Edited by admin on Sat Dec 16 02:19:02 GMT 2023
PRIMARY
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TARGET -> INHIBITOR
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
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ACTIVE MOIETY