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Details

Stereochemistry ACHIRAL
Molecular Formula C21H22N6O3.C4H11NO3
Molecular Weight 527.5728
Optical Activity NONE
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of OSI-027 TROMETHAMINE

SMILES

NC(CO)(CO)CO.COC1=CC=CC2=C1NC(=C2)C3=C4N(N=CN=C4N)C(=N3)[C@H]5CC[C@@H](CC5)C(O)=O

InChI

InChIKey=YMQRKUUPKVIYHX-GJTSMBTKSA-N
InChI=1S/C21H22N6O3.C4H11NO3/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;5-4(1-6,2-7)3-8/h2-4,9-12,25H,5-8H2,1H3,(H,28,29)(H2,22,23,24);6-8H,1-3,5H2/t11-,12-;

HIDE SMILES / InChI

Molecular Formula C4H11NO3
Molecular Weight 121.135
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C21H22N6O3
Molecular Weight 406.4378
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity NONE

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
Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin.
2011 Aug
OSI-027 inhibits pancreatic ductal adenocarcinoma cell proliferation and enhances the therapeutic effect of gemcitabine both in vitro and in vivo.
2015 Sep 22
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 19:05:11 GMT 2023
Edited
by admin
on Sat Dec 16 19:05:11 GMT 2023
Record UNII
3Z35AM5LYU
Record Status Validated (UNII)
Record Version
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Name Type Language
OSI-027 TROMETHAMINE
Common Name English
OSI-027 TROMETHAMINE SALT
Common Name English
CYCLOHEXANECARBOXYLIC ACID, 4-(4-AMINO-5-(7-METHOXY-1H-INDOL-2-YL)IMIDAZO(5,1-F)(1,2,4)TRIAZIN-7-YL)-, TRANS-, COMPD. WITH 2-AMINO-2-(HYDROXYMETHYL)-1,3-PROPANEDIOL (1:1)
Systematic Name English
CERC-006 TROMETHAMINE
Code English
AEVI-006 TROMETHAMINE
Code English
Code System Code Type Description
FDA UNII
3Z35AM5LYU
Created by admin on Sat Dec 16 19:05:11 GMT 2023 , Edited by admin on Sat Dec 16 19:05:11 GMT 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
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ACTIVE MOIETY