OSI-027

Investigational

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 Search

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26213847 | https://www.ncbi.nlm.nih.gov/pubmed/26284306

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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Mammalian target of Rapamycin (mTORC1) 23 Target ID: CHEMBL2221341 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21673091	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Lymphoma 58 Sources: https://clinicaltrials.gov/ct2/show/NCT00698243	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	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	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

T_1/2

Value	Dose	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

Sourcing

Vendor/Aggregator	ID	URL
AK Scientific	2616AH	https://aksci.com/item_detail.php?cat=2616AH
AK Scientific	X7443	https://aksci.com/item_detail.php?cat=X7443
BLD Pharm	BD306064	http://www.bldpharm.com/search/Search.html?keyword=BD306064
Selleck Chemicals	S2624	http://www.selleckchem.com/search.html?searchDTO.searchParam=S2624
Toronto Research Chemicals	D226850	https://www.trc-canada.com/product-detail/?CatNum=D226850
eMolecules	300606980	https://orderbb.emolecules.com/search/#?query=300606980
eMolecules	44696697	https://orderbb.emolecules.com/search/#?query=44696697
eMolecules	68829805	https://orderbb.emolecules.com/search/#?query=68829805

PubMed

Title	Date	PubMed
Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin.	2011 Aug	21673091
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	21322566
The Antipancreatic Cancer Activity of OSI-027, a Potent and Selective Inhibitor of mTORC1 and mTORC2.	2015 Oct	26284306
OSI-027 inhibits pancreatic ductal adenocarcinoma cell proliferation and enhances the therapeutic effect of gemcitabine both in vitro and in vivo.	2015 Sep 22	26213847
A first in man, dose-finding study of the mTORC1/mTORC2 inhibitor OSI-027 in patients with advanced solid malignancies.	2016 Apr 12	27002938

Patents

Sample Use Guides

In Vivo Use Guide

30 mg per day, once daily

Route of Administration: Oral

In Vitro Use Guide

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