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

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
Discovery and SAR exploration of a novel series of imidazo[4,5-b]pyrazin-2-ones as potent and selective mTOR kinase inhibitors.	2011 Nov 15	21978683
Mammalian target of rapamycin inhibition in hepatocellular carcinoma.	2014 Nov 27	25429315
Discovery of mammalian target of rapamycin (mTOR) kinase inhibitor CC-223.	2015 Jul 9	26083478
CC-223, a Potent and Selective Inhibitor of mTOR Kinase: In Vitro and In Vivo Characterization.	2015 Jun	25855786
A phase I dose-escalation study to assess safety, tolerability, pharmacokinetics, and preliminary efficacy of the dual mTORC1/mTORC2 kinase inhibitor CC-223 in patients with advanced solid tumors or multiple myeloma.	2015 Oct 1	26177599

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).

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