Prexasertib

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H19N7O2
Molecular Weight	365.3892
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=CC(OCCCN)=C1C2=CC(NC3=CN=C(C=N3)C#N)=NN2

InChI

InChIKey=DOTGPNHGTYJDEP-UHFFFAOYSA-N

InChI=1S/C18H19N7O2/c1-26-14-4-2-5-15(27-7-3-6-19)18(14)13-8-16(25-24-13)23-17-11-21-12(9-20)10-22-17/h2,4-5,8,10-11H,3,6-7,19H2,1H3,(H2,22,23,24,25)

HIDE SMILES / InChI

Description
Sources: http://www.lillyoncologypipeline.com/molecule/chk-1-inhibitor/overview

LY2606368 (Prexasertib) is a small-molecule Chk-1 inhibitors invented by Array and being developed by Eli Lilly and Company. Lilly is responsible for all clinical development and commercialization activities. LY2606368 is advancing in Phase 2 clinical trials for cancer. Prexasertib preferentially binds to and inhibits CHK1 and, to a lesser extent, inhibits CHK2. Chk-1 is a protein kinase that regulates the tumor cell's response to DNA damage often caused by treatment with chemotherapy. In response to DNA damage, Chk-1 blocks cell cycle progression in order to allow for repair of damaged DNA, thereby limiting the efficacy of chemotherapeutic agents. Inhibiting Chk-1 in combination with chemotherapy can enhance tumor cell death by preventing these cells from recovering from DNA damage.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine/threonine-protein kinase Chk1 20 Target ID: CHEMBL4630 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=26141948	Inhibitor 8297		0.9 nM [Ki]
Serine/threonine-protein kinase Chk2 9 Target ID: CHEMBL2527 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=26141948	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Breast cancer 434 Sources: https://clinicaltrials.gov/ct2/show/NCT02203513	Primary	Phase III 656	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: https://clinicaltrials.gov/ct2/show/NCT02203513	Primary	Phase II 1132	Unknown Approved Use Unknown
Castrate-resistant prostate cancer 20 Sources: https://clinicaltrials.gov/ct2/show/NCT02203513	Primary	Phase II 1132	Unknown Approved Use Unknown
Small-cell lung cancer 41 Sources: https://clinicaltrials.gov/ct2/show/NCT02735980	Primary	Phase II 1132	Unknown Approved Use Unknown

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P009CTI	https://www.1pchem.com/search?query=1P009CTI
1PlusChem LLC	1P009CZL	https://www.1pchem.com/search?query=1P009CZL
AOBIOUS INC	AOB87325	http://aobious.com/aobious/search?search_query=AOB87325
ApexBio Technology	B1088	https://www.apexbt.com/catalogsearch/result/?q=B1088
ApexBio Technology	B8313	https://www.apexbt.com/catalogsearch/result/?q=B8313
AstaTech	40915	http://astatechinc.com/CPSResult.php?CRNO=40915
AstaTech	49915	http://astatechinc.com/CPSResult.php?CRNO=49915
BLD Pharm	BD566146	http://www.bldpharm.com/search/Search.html?keyword=BD566146
Chem Scene	CS-0130202	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0130202
Chem Scene	CS-2198	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-2198
Chem Scene	CS-3507	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3507
ChemShuttle	157219	https://www.chemshuttle.com/catalogsearch/result/?q=157219
ChemShuttle	186097	https://www.chemshuttle.com/catalogsearch/result/?q=186097
Excenen	EX-A758	http://www.excenen.com/searchresultlist.php?id=EX-A758
Lab Network	LN01342665	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01342665
MedChem Express	HY-18174A	https://www.medchemexpress.com/search.html?q=HY-18174A&ft=&fa=&fp=
MedChem Express	HY-18174	https://www.medchemexpress.com/search.html?q=HY-18174E&ft=&fa=&fp=
MedChem Express	HY-18174E	https://www.medchemexpress.com/search.html?q=HY-18174E&ft=&fa=&fp=
MolPort	MolPort-044-727-625	https://www.molport.com/shop/molecule-link/MolPort-044-727-625
MolPort	MolPort-044-830-662	https://www.molport.com/shop/molecule-link/MolPort-044-830-662
Molnova	M10928	https://www.molnova.com/en/serch-list.html?keywords=M10928
Molnova	M10929	https://www.molnova.com/en/serch-list.html?keywords=M10929
MuseChem	I008871	https://www.musechem.com/product/I008871.html
MuseChem	I008872	https://www.musechem.com/product/I008872.html
MuseChem	I008873	https://www.musechem.com/product/I008873.html
ShangHai Biochempartner	BCP14380	http://www.biochempartner.com/search_BCP14380
ShangHai Biochempartner	BCP15627	http://www.biochempartner.com/search_BCP15627
ShangHai Biochempartner	BCP24330	http://www.biochempartner.com/search_BCP24330
TargetMol	T4310	https://www.targetmol.com/search?keyword=T4310
TargetMol	T4327	https://www.targetmol.com/search?keyword=T4327
Toronto Research Chemicals	B697028	https://www.trc-canada.com/product-detail/?CatNum=B697028
Toronto Research Chemicals	L486550	https://www.trc-canada.com/product-detail/?CatNum=L486550
Toronto Research Chemicals	P713513	https://www.trc-canada.com/product-detail/?CatNum=P713513
eMolecules	271446146	https://orderbb.emolecules.com/search/#?query=271446146
eMolecules	300958586	https://orderbb.emolecules.com/search/#?query=300958586
eMolecules	48584148	https://orderbb.emolecules.com/search/#?query=48584148
eMolecules	48670839	https://orderbb.emolecules.com/search/#?query=48670839
eMolecules	50284392	https://orderbb.emolecules.com/search/#?query=50284392
eNovation Chemicals	D501863	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501863&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-4465783011	https://mcule.com/MCULE-4465783011/
mcule	MCULE-8813918961	https://mcule.com/MCULE-8813918961/
mcule	MCULE-9787336199	https://mcule.com/MCULE-9787336199/

PubMed

Title	Date	PubMed
Prexasertib, a Chk1/Chk2 inhibitor, increases the effectiveness of conventional therapy in B-/T- cell progenitor acute lymphoblastic leukemia.	2016 Aug 16	27438145

Patents

Sample Use Guides

In Vivo Use Guide

105 mg/m2 IV once every 14 days of a 28 day cycle

Route of Administration: Intravenous

In Vitro Use Guide

In a functional assay, LY2606368 (PREXASERTIB) potently abrogated the G2–M checkpoint activated by doxorubicin in p53-deficient HeLa cells with an EC50 of 9 nmol/L. LY2606368 did inhibit DNA damage-induced CHK2 autophosphorylation with an IC50 of less than 31 nmol/L. 100 nmol/L LY2606368 did not inhibit PMA-stimulated RSK but instead weakly stimulated phosphorylation of S6 on serines 235/236. LY2606368 was broadly antiproliferative with IC50 values typically <50 nmol/L in the most sensitive cell lines with a minority of cell lines showing considerable resistance with IC50's >1,000 nmol/L

Name

Type

Language

Prexasertib

Official Name

English

LY2606368

Code

English

prexasertib [INN]

Common Name

English

Prexasertib [WHO-DD]

Common Name

English

LY-2606368

Code

English

5-[[5-[2-(3-Aminopropoxy)-6-methoxyphenyl]-1H-pyrazol-3-yl]amino]-2-pyrazinecarbonitrile

Systematic Name

English

2-Pyrazinecarbonitrile, 5-[[5-[2-(3-aminopropoxy)-6-methoxyphenyl]-1H-pyrazol-3-yl]amino]-

Systematic Name

English

PREXASERTIB [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C129825