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

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

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Description

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	Inhibitor 8,504

Conditions

Condition	Modality	Highest Phase	Product
Pancreatic cancer 98	Primary	Phase II 1,147	Unknown
Non-small cell lung cancer 211	Primary	Phase II 1,147	Unknown
Solid tumors 147	Primary	Phase I 438	Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
3170 ng/mL	230 mg 3 times / 4 weeks steady-state, intravenous	GEMCITABINE	RABUSERTIB plasma	Homo sapiens
3430 ng/mL	150 mg/m² 1 times / 3 weeks steady-state, intravenous	PEMETREXED	RABUSERTIB plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
29400 ng × h/mL	230 mg 3 times / 4 weeks steady-state, intravenous	GEMCITABINE	RABUSERTIB plasma	Homo sapiens
38000 ng × h/mL	150 mg/m² 1 times / 3 weeks steady-state, intravenous	PEMETREXED	RABUSERTIB plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
9.67 h	230 mg 3 times / 4 weeks steady-state, intravenous	GEMCITABINE	RABUSERTIB plasma	Homo sapiens
14.4 h	150 mg/m² 1 times / 3 weeks steady-state, intravenous	PEMETREXED	RABUSERTIB plasma	Homo sapiens

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,946	substrate 1,193	substrate 1,388 inhibitor 2,507	inhibitor 2,217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1,741 CYP1A2 2,153	CYP2C19 1,119 CYP3A5 446 CYP2C8 810 CYP1A2 1,197 CYP2J2 71 CYP2B6 776 CYP2E1 729

Drug as perpetrator

Show entries

Target	Modality	Activity	Clinical evidence
P-gp 1,932	inhibitor 4,027	inconclusive [IC50 10.4904 uM]
CYP1A2 2,333	inhibitor 4,027	yes [Ki 4 uM]
CYP2D6 2,546	inhibitor 4,027	yes [Ki 8.8 uM]	yes (co-administration study)

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Drug as victim

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Target	Modality	Activity
CYP3A4 1,946	substrate 4,014	major
CYP2D6 1,388	substrate 4,014	minor
CYP1A2 1,197	substrate 4,014	no
CYP2B6 776	substrate 4,014	no
CYP2C19 1,119	substrate 4,014	no

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2,263	inhibitor 2,237

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Sourcing

Sourcing

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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

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PubMed

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Title	Date	PubMed
Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor.	2014 Apr	24114124

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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

Show entries

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

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Classification Tree

Code System

Code

Antineoplastic Protein Inhibitor

NCI_THESAURUS

C129825

Protein Kinase Inhibitor

NCI_THESAURUS

C61074

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Code System

Code

Type

Description

ChEMBL

CHEMBL3039517

PRIMARY

CAS

911222-45-2

PRIMARY

USAN

YY-50

PRIMARY

EPA CompTox

DTXSID50238417

PRIMARY

INN

9561

PRIMARY

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ACTIVE MOIETY


					3S9L1NU6U7

RABUSERTIB

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

Drug as perpetrator