RABUSERTIB

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H22BrN5O3
Molecular Weight	436.303
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CN=C(NC(=O)NC2=CC(Br)=C(C)C=C2OC[C@@H]3CNCCO3)C=N1

InChI

InChIKey=SYYBDNPGDKKJDU-ZDUSSCGKSA-N

InChI=1S/C18H22BrN5O3/c1-11-5-16(27-10-13-8-20-3-4-26-13)15(6-14(11)19)23-18(25)24-17-9-21-12(2)7-22-17/h5-7,9,13,20H,3-4,8,10H2,1-2H3,(H2,22,23,24,25)/t13-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C18H22BrN5O3
Molecular Weight	436.303
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://adisinsight.springer.com/drugs/800026833 | https://www.ncbi.nlm.nih.gov/pubmed/25315907 | http://216.139.227.101/interactive/arry2007/pf/page_019.pdf

Rabusertib is a Chk1 kinase inhibitor which was developed by ICOS for the treatment of cancer. The drug was tested in phase II of clinical trials for pancreatic cancer and non small cell lung carcinoma, but its development was discontinued. Now the drug is undergoing phase I trial in Japanese patients with solid tumors.

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/24114124	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Pancreatic cancer 97 Sources: https://clinicaltrials.gov/ct2/show/NCT00839332	Primary	Phase II 1132	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: https://clinicaltrials.gov/ct2/show/NCT00988858	Primary	Phase II 1132	Unknown Approved Use Unknown
Solid tumors 145 Sources: https://clinicaltrials.gov/ct2/show/NCT01341457	Primary	Phase I 428	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461	CYP2C19 991 CYP3A5 395 CYP2C8 693 CYP1A2 1054 CYP2J2 56 CYP2B6 664 CYP2E1 667 AO 16

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174007107	inconclusive [IC50 10.4904 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/25296725/	no		yes (co-administration study) Comment: Rabusertib increased Desipramine Cmax and AUCinf by 11% and 8%. Sources: https://pubmed.ncbi.nlm.nih.gov/25296725/

Drug as victim

Target	Modality	Activity
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	major
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	minor
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	no
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	no
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	no
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	no
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	no
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	no
CYP2J2 56	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	no
CYP3A5 395	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	no
AO 16	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/30986571/

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00GUKT	https://www.1pchem.com/search?query=1P00GUKT
AChemBlock	O32848	http://www.achemblock.com/catalogsearch/result/?q=O32848
Ambeed	A141550	http://www.ambeed.com/search/Search.html?keyword=A141550
Angene	AGN-PC-0WH9M2	http://www.angenechemical.com/productshow/AGN-PC-0WH9M2.html
ApexBio Technology	A8638	https://www.apexbt.com/catalogsearch/result/?q=A8638
AstaTech	C77108	http://astatechinc.com/CPSResult.php?CRNO=C77108
BLD Pharm	BD559083	http://www.bldpharm.com/search/Search.html?keyword=BD559083
BOC Sciences	911222-45-2	http://www.bocsci.com/description.asp?cas=911222-45-2
Cayman Chemical	20351	http://www.caymanchem.com/app/template/Product.vm/catalog/20351
Chem Scene	CS-0472	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0472
ChemShuttle	109787	https://www.chemshuttle.com/catalogsearch/result/?q=109787
Debye Scientific	DA-40638	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-40638
KeyOrganics	AS-56111	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-56111
Matrix Scientific	146681	http://www.matrixscientific.com/146681.html
MedChem Express	HY-14720	https://www.medchemexpress.com/search.html?q=HY-14720&ft=&fa=&fp=
MolPort	MolPort-021-804-967	https://www.molport.com/shop/molecule-link/MolPort-021-804-967
Molnova	M16540	https://www.molnova.com/en/serch-list.html?keywords=M16540
Selleck Chemicals	S2626	http://www.selleckchem.com/search.html?searchDTO.searchParam=S2626
ShangHai Biochempartner	BCP000383	http://www.biochempartner.com/search_BCP000383
TargetMol	T6084	https://www.targetmol.com/search?keyword=T6084
Toronto Research Chemicals	L503115	https://www.trc-canada.com/product-detail/?CatNum=L503115
eMolecules	195316607	https://orderbb.emolecules.com/search/#?query=195316607
eMolecules	300564808	https://orderbb.emolecules.com/search/#?query=300564808
eMolecules	37153195	https://orderbb.emolecules.com/search/#?query=37153195
eNovation Chemicals	D372400	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D372400&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-2371680090	https://mcule.com/MCULE-2371680090/
mcule	MCULE-6324300695	https://mcule.com/MCULE-6324300695/

PubMed

Title	Date	PubMed
New insights into checkpoint kinase 1 in the DNA damage response signaling network.	2010 Jan 15	20068082
Summary of presentation from the targeted therapy in lung cancer meeting.	2011 Nov	22005528
Cellular impedance assays for predictive preclinical drug screening of kinase inhibitor cardiovascular toxicity.	2013 Oct	23897988
Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor.	2014 Apr	24114124

Patents

Sample Use Guides

In Vivo Use Guide

170 or 230 mg of rabusertib are administered intravenously on days 2, 9 and 16 of at least one 28-day cycle (in combination with gemcitabine).

Route of Administration: Intravenous

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:38:03 GMT 2023` Edited by `admin` on `Fri Dec 15 15:38:03 GMT 2023`
Record UNII	3S9L1NU6U7
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

RABUSERTIB

Official Name

English

rabusertib [INN]

Common Name

English

1-(5-BROMO-4-METHYL-2-((2S)-MORPHOLIN-2-YLMETHOXY)PHENYL)-3-(5-METHYLPYRAZIN-2-YL)UREA

Systematic Name

English

LY2603618

Code

English

IC-83

Code

English

RABUSERTIB [USAN]

Common Name

English

LY-2603618

Code

English

Rabusertib [WHO-DD]

Common Name

English

UREA, N-(5-BROMO-4-METHYL-2-((2S)-2-MORPHOLINYLMETHOXY)PHENYL)-N'-(5-METHYL-2- PYRAZINYL)-

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C129825