RABUSERTIB

Investigational

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 23 Target ID: CHEMBL4630 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24114124	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Pancreatic cancer 98 Sources: https://clinicaltrials.gov/ct2/show/NCT00839332	Primary	Phase II 1147	Unknown Approved Use Unknown
Non-small cell lung cancer 211 Sources: https://clinicaltrials.gov/ct2/show/NCT00988858	Primary	Phase II 1147	Unknown Approved Use Unknown
Solid tumors 147 Sources: https://clinicaltrials.gov/ct2/show/NCT01341457	Primary	Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
3170 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28202004/	230 mg 3 times / 4 weeks steady-state, intravenous dose: 230 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered: GEMCITABINE	GEMCITABINE	RABUSERTIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3430 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27350064	150 mg/m² 1 times / 3 weeks steady-state, intravenous dose: 150 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered: PEMETREXED	PEMETREXED	RABUSERTIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
29400 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28202004/	230 mg 3 times / 4 weeks steady-state, intravenous dose: 230 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered: GEMCITABINE	GEMCITABINE	RABUSERTIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
38000 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27350064	150 mg/m² 1 times / 3 weeks steady-state, intravenous dose: 150 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered: PEMETREXED	PEMETREXED	RABUSERTIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
9.67 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28202004/	230 mg 3 times / 4 weeks steady-state, intravenous dose: 230 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered: GEMCITABINE	GEMCITABINE	RABUSERTIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.4 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27350064	150 mg/m² 1 times / 3 weeks steady-state, intravenous dose: 150 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered: PEMETREXED	PEMETREXED	RABUSERTIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 CYP1A2 2153	CYP2C19 1119 CYP3A5 446 CYP2C8 810 CYP1A2 1197 CYP2J2 71 CYP2B6 776 CYP2E1 729

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174007107	inconclusive [IC50 10.4904 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/25296725/	yes [Ki 4 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/25296725/	yes [Ki 8.8 uM]	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 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	major
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	minor
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	no
CYP2B6 776	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	no
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	no
CYP2C8 810	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	no
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	no
CYP2E1 729	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	no
CYP2J2 71	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	no
CYP3A5 446	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24666335/	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 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
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
KeyOrganics	AS-56111	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-56111
Matrix Scientific	146681	http://www.matrixscientific.com/146681.html
mcule	MCULE-2371680090	https://mcule.com/MCULE-2371680090/
mcule	MCULE-6324300695	https://mcule.com/MCULE-6324300695/
MedChem Express	HY-14720	https://www.medchemexpress.com/search.html?q=HY-14720&ft=&fa=&fp=
Molnova	M16540	https://www.molnova.com/en/serch-list.html?keywords=M16540
MolPort	MolPort-021-804-967	https://www.molport.com/shop/molecule-link/MolPort-021-804-967
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

PubMed

Title	Date	PubMed
Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor.	2014-04	24114124
Cellular impedance assays for predictive preclinical drug screening of kinase inhibitor cardiovascular toxicity.	2013-10	23897988
Summary of presentation from the targeted therapy in lung cancer meeting.	2011-11	22005528
New insights into checkpoint kinase 1 in the DNA damage response signaling network.	2010-01-15	20068082

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 `Mon Mar 31 18:03:45 GMT 2025` Edited by `admin` on `Mon Mar 31 18:03:45 GMT 2025`
Record UNII	3S9L1NU6U7
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

RABUSERTIB

Official Name

English

IC-83

Preferred 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

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