CC-115

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H16N8O
Molecular Weight	336.3512
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN1C(=O)CNC2=C1N=C(C=N2)C3=C(C)N=C(C=C3)C4=NN=CN4

InChI

InChIKey=GMYLVKUGJMYTFB-UHFFFAOYSA-N

InChI=1S/C16H16N8O/c1-3-24-13(25)7-18-15-16(24)22-12(6-17-15)10-4-5-11(21-9(10)2)14-19-8-20-23-14/h4-6,8H,3,7H2,1-2H3,(H,17,18)(H,19,20,23)

HIDE SMILES / InChI

Molecular Formula	C16H16N8O
Molecular Weight	336.3512
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27235137

CC-115 is a recently identified inhibitor of the mammalian Target of Rapamycin Kinase (TORK) and DNA-Dependent Protein Kinase (DNA-PK). It is under investigation in phase II clinical trials for the treatment for Glioblastoma and in phase I trials for the treatment of prostate cancer, Ewing's, Osteosarcoma, Chronic Lymphocytic Leukemia and Squamous Cell Carcinoma of the Head and Neck.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine/threonine-protein kinase mTOR 35 Target ID: P42345 Gene ID: 2475.0 Gene Symbol: MTOR Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26102506	Inhibitor 8297		0.021 µM [IC50]
DNA-dependent protein kinase catalytic subunit 4 Target ID: P78527\|\|\|Q9UME3 Gene ID: 5591.0 Gene Symbol: PRKDC Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26102506	Inhibitor 8297		0.013 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Chronic lymphocytic leukemia 59 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27235137	Primary	Phase I 428	Unknown Approved Use Unknown
Prostate cancer 178 Sources: https://clinicaltrials.gov/show/NCT01353625	Primary	Phase I 428	Unknown Approved Use Unknown
Ewing's osteosarcom 1 Sources: https://clinicaltrials.gov/show/NCT01353625	Primary	Phase I 428	Unknown Approved Use Unknown
Glioblastoma 65 Sources: https://clinicaltrials.gov/ct2/show/NCT02977780	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
173 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31853198	25 mg 1 times / day single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	CC-115 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
162 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31853198	15 mg 2 times / day multiple, oral dose: 15 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CC-115 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
244 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31853198	40 mg 1 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CC-115 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
51.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31853198	10 mg 2 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CC-115 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
75.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31853198	10 mg 2 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CC-115 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
198 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31853198	25 mg 1 times / day multiple, oral dose: 25 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CC-115 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
1716 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31853198	25 mg 1 times / day single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	CC-115 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2056 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31853198	15 mg 2 times / day multiple, oral dose: 15 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CC-115 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2650 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31853198	40 mg 1 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CC-115 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
622 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31853198	10 mg 2 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CC-115 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
66 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31853198	10 mg 2 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CC-115 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1573 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31853198	25 mg 1 times / day multiple, oral dose: 25 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CC-115 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31853198	25 mg 1 times / day single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		CC-115 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3.98 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31853198	10 mg 2 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:		CC-115 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P000JYN	https://www.1pchem.com/search?query=1P000JYN
1PlusChem LLC	1P009D1L	https://www.1pchem.com/search?query=1P009D1L
AChemBlock	O33758	http://www.achemblock.com/catalogsearch/result/?q=O33758
ApexBio Technology	B6114	https://www.apexbt.com/catalogsearch/result/?q=B6114
AstaTech	44159	http://astatechinc.com/CPSResult.php?CRNO=44159
BLD Pharm	BD630024	http://www.bldpharm.com/search/Search.html?keyword=BD630024
BLD Pharm	BD630098	http://www.bldpharm.com/search/Search.html?keyword=BD630098
Cayman Chemical	19420	http://www.caymanchem.com/app/template/Product.vm/catalog/19420
Chem Scene	CS-4561	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-4561
Chem Scene	CS-5379	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-5379
ChemShuttle	140477	https://www.chemshuttle.com/catalogsearch/result/?q=140477
KeyOrganics	AS-74848	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-74848
Lab Network	LN01341555	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01341555
MedChem Express	HY-16962	https://www.medchemexpress.com/search.html?q=HY-16962A&ft=&fa=&fp=
MedChem Express	HY-16962A	https://www.medchemexpress.com/search.html?q=HY-16962A&ft=&fa=&fp=
MolPort	MolPort-044-183-473	https://www.molport.com/shop/molecule-link/MolPort-044-183-473
MolPort	MolPort-044-560-393	https://www.molport.com/shop/molecule-link/MolPort-044-560-393
MolPort	MolPort-046-033-571	https://www.molport.com/shop/molecule-link/MolPort-046-033-571
MolPort	MolPort-046-417-172	https://www.molport.com/shop/molecule-link/MolPort-046-417-172
MolPort	MolPort-046-702-084	https://www.molport.com/shop/molecule-link/MolPort-046-702-084
Molnova	M10883	https://www.molnova.com/en/serch-list.html?keywords=M10883
Molnova	M11206	https://www.molnova.com/en/serch-list.html?keywords=M11206
MuseChem	I005747	https://www.musechem.com/product/I005747.html
ShangHai Biochempartner	BCP16702	http://www.biochempartner.com/search_BCP16702
ShangHai Biochempartner	BCP20709	http://www.biochempartner.com/search_BCP20709
eMolecules	106929350	https://orderbb.emolecules.com/search/#?query=106929350
eMolecules	208087683	https://orderbb.emolecules.com/search/#?query=208087683
eMolecules	222564514	https://orderbb.emolecules.com/search/#?query=222564514
eMolecules	75542243	https://orderbb.emolecules.com/search/#?query=75542243
eMolecules	89941990	https://orderbb.emolecules.com/search/#?query=89941990
mcule	MCULE-3559529294	https://mcule.com/MCULE-3559529294/
mcule	MCULE-6536966585	https://mcule.com/MCULE-6536966585/

PubMed

Title	Date	PubMed
Reversible thiazolidine exchange: a new reaction suitable for dynamic combinatorial chemistry.	2009 Aug 6	19585999
Optimization of a Series of Triazole Containing Mammalian Target of Rapamycin (mTOR) Kinase Inhibitors and the Discovery of CC-115.	2015 Jul 23	26102506
Dual TORK/DNA-PK inhibition blocks critical signaling pathways in chronic lymphocytic leukemia.	2016 Jul 28	27235137

Sample Use Guides

In Vivo Use Guide

Dose level starts with 0.5mg daily by mouth in cycles of 28 days. Level increases for different patient cohorts in 100% or 50% increments until optimal dose schedule is established for further study. Treatment continues for as long as patient benefits (i.e., until disease progression or unacceptable toxicity).

Route of Administration: Oral

In Vitro Use Guide

To determine whether combined inhibition of TORK and DNA-PK induces cell death, there were compared CC-115 (range of concentration from 0.001 until 10 uM) to inhibitors that are more specific: CC-214, CC-292, idelalisisb, and NU7441. To correct for variability in viability between thawed primary chronic lymphocytic leukemia (CLL) samples, specific apoptosis was calculated. CC-214 (TORKi), CC-292 (BTKi), idelalisib (PI3Kδi), and NU7441 (DNAPKi) induced modest cell death (IC50 > 10 µM and maximum induction of apoptosis at 10 µM of 30-40 %. Whereas CC-115 induced cell death with an IC50 of 0.51 µM. Cell death was due to on-target inhibition of TORK and DNA-PK, because the combination of the TORK inhibitor CC-214 and the DNA-PK inhibitor NU7441 resulted in cell death comparable to CC-115. CC-115 induced cell death in clinically relevant prognostic CLL subgroups.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:26:44 GMT 2023` Edited by `admin` on `Sat Dec 16 08:26:44 GMT 2023`
Record UNII	FII75TFH5L
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

CC-115

Common Name

English

CC-115 [WHO-DD]

Common Name

English

1-ETHYL-7-(2-METHYL-6-(1H-1,2,4-TRIAZOL-3-YL)PYRIDIN-3-YL)-3,4-DIHYDROPYRAZINO(2,3-B)PYRAZIN-2(1H)-ONE

Systematic Name

English

PYRAZINO(2,3-B)PYRAZIN-2(1H)-ONE, 1-ETHYL-3,4-DIHYDRO-7-(2-METHYL-6-(1H-1,2,4-TRIAZOL-5-YL)-3-PYRIDINYL)-

Systematic Name

English

1-ETHYL-7-(2-METHYL-6-(4H-1,2,4-TRIAZOL-3-YL)PYRIDIN-3-YL)-3,4-DIHYDROPYRAZINO(2,3-B)PYRAZIN-2(1H)-ONE

Systematic Name

English

Code System Code Type Description

DRUG BANK

DB12740