ONATASERTIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H27N5O3
Molecular Weight	397.4708
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CO[C@H]1CC[C@@H](CC1)N2C(=O)CNC3=C2N=C(C=N3)C4=CN=C(C=C4)C(C)(C)O

InChI

InChIKey=UFKLYTOEMRFKAD-SHTZXODSSA-N

InChI=1S/C21H27N5O3/c1-21(2,28)17-9-4-13(10-22-17)16-11-23-19-20(25-16)26(18(27)12-24-19)14-5-7-15(29-3)8-6-14/h4,9-11,14-15,28H,5-8,12H2,1-3H3,(H,23,24)/t14-,15-

HIDE SMILES / InChI

Molecular Formula	C21H27N5O3
Molecular Weight	397.4708
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=683644 | https://www.ncbi.nlm.nih.gov/pubmed/26177599 |https://www.ncbi.nlm.nih.gov/pubmed/28334043 | http://adisinsight.springer.com/drugs/800029645

CC-223 is an orally available inhibitor of the mammalian target of rapamycin (mTOR) with potential antineoplastic activity. mTOR kinase inhibitor CC-223 inhibits the activity of mTOR, which may result in the induction of tumor cell apoptosis and a decrease in tumor cell proliferation. CC-223 disrupted mitochondrial function, and induced mitochondrial permeability transition pore (mPTP) opening and reactive oxygen species (ROS) production. CC-223 is currently in phase II clinical trials for the treatment of Multiple myeloma; Non-Hodgkin's lymphoma; Solid tumours. The most common treatment-related adverse events were hyperglycemia, fatigue and rash.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serine/threonine-protein kinase mTOR 35 Target ID: CHEMBL2842 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25855786	Inhibitor 8297	16.0 nM [IC50]
PI3-kinase p110-alpha subunit 41 Target ID: CHEMBL4005 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25855786	Inhibitor 8297	4.0 µM [IC50]
DNA-dependent protein kinase 11 Target ID: CHEMBL3142 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25855786	Inhibitor 8297	0.84 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Multiple myeloma 159 Sources: http://adisinsight.springer.com/drugs/800029645 https://www.ncbi.nlm.nih.gov/pubmed/26177599	Primary	Phase II 1132	Unknown Approved Use Unknown
Non-Hodgkin's lymphoma 79 Sources: http://adisinsight.springer.com/trials/700058533	Primary	Phase II 1132	Unknown Approved Use Unknown
Solid tumors 145 Sources: http://adisinsight.springer.com/trials/700058533 https://www.ncbi.nlm.nih.gov/pubmed/26177599	Primary	Phase II 1132	Unknown Approved Use Unknown

Sourcing

Vendor/Aggregator	ID	URL
Selleck Chemicals	S7886	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7886
eMolecules	303168997	https://orderbb.emolecules.com/search/#?query=303168997
eMolecules	72973034	https://orderbb.emolecules.com/search/#?query=72973034
eMolecules	95741244	https://orderbb.emolecules.com/search/#?query=95741244

PubMed

Title	Date	PubMed
Mammalian target of rapamycin inhibition in hepatocellular carcinoma.	2014 Nov 27	25429315
CC-223, a Potent and Selective Inhibitor of mTOR Kinase: In Vitro and In Vivo Characterization.	2015 Jun	25855786

Patents

Sample Use Guides

In Vivo Use Guide

20 mg or 30 mg once daily.

Route of Administration: Oral

In Vitro Use Guide

CC-223 showed a concentration-dependent reduction in each marker, with IC50 values of 31 nmol/L for pS6RP, 405 47 nmol/L for p4EBP1, and 11 10 nmol/L for pAKT(S473). CC-223 inhibited both mTORC1 (S6RP and 4EBP1) and mTORC2 [AKT(S473)] markers across the panel with IC50 ranges of 27 to 184 nmol/L for pS6RP, 120 to 1,050 nmol/L for p4EBP1 and 11 to 150 nmol/L for pAKT (S473).

Substance Class	Chemical Created by `admin` on `Sat Dec 16 11:00:26 GMT 2023` Edited by `admin` on `Sat Dec 16 11:00:26 GMT 2023`
Record UNII	I8RA3543SY
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ONATASERTIB

Official Name

English

CC-223

Preferred Name

English

ONATASERTIB [USAN]

Common Name

English

ATG008

Code

English

CC223

Code

English

ONATASERTIB [WHO-DD]

Common Name

English

7-[6-(2-Hydroxypropan-2-yl)pyridin-3-yl]-1-(trans-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

Systematic Name

English

PYRAZINO(2,3-B)PYRAZIN-2(1H)-ONE, 3,4-DIHYDRO-7-(6-(1-HYDROXY-1-METHYLETHYL)-3-PYRIDINYL)-1-(TRANS-4-METHOXYCYCLOHEXYL)-

Systematic Name

English

ATG-008

Code

English

3,4-DIHYDRO-7-(6-(1-HYDROXY-1-METHYLETHYL)-3-PYRIDINYL)-1-(TRANS-4-METHOXYCYCLOHEXYL)PYRAZINO(2,3-B)PYRAZIN-2(1H)-ONE

Systematic Name

English

onatasertib [INN]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

407913