General Information of Drug (ID: DMCXRZF)

Drug Name
LY2603618
Synonyms
LY2603618; Rabusertib; 911222-45-2; LY 2603618; LY-2603618; UNII-3S9L1NU6U7; 3S9L1NU6U7; IC-83; ly2603618 IC-83; (S)-1-(5-bromo-4-methyl-2-(morpholin-2-ylmethoxy)phenyl)-3-(5-methylpyrazin-2-yl)urea; n-(5-bromo-4-methyl-2-((2s)-2-morpholinylmethoxy)phenyl)-n'-(5-methyl-2-pyrazinyl)urea; LY2603618 (IC-83); Rabusertib [USAN:INN]; 3-(5-Bromo-4-methyl-2-[(2s)-morpholin-2-ylmethoxy]phenyl)-1-(5-methylpyrazin-2-yl)urea; N-[5-Bromo-4-methyl-2-[(2S)-2-morpholinylmethoxy)phenyl]-N'-(5-methyl-2-pyrazinyl)urea
Indication
Disease Entry ICD 11 Status REF
Pancreatic cancer 2C10 Phase 2 [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL is unavailable 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 436.3
Topological Polar Surface Area (xlogp) 1.4
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 6
Chemical Identifiers
Formula
C18H22BrN5O3
IUPAC Name
1-[5-bromo-4-methyl-2-[[(2S)-morpholin-2-yl]methoxy]phenyl]-3-(5-methylpyrazin-2-yl)urea
Canonical SMILES
CC1=CC(=C(C=C1Br)NC(=O)NC2=NC=C(N=C2)C)OC[C@@H]3CNCCO3
InChI
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
InChIKey
SYYBDNPGDKKJDU-ZDUSSCGKSA-N
Cross-matching ID
PubChem CID
11955855
ChEBI ID
CHEBI:124917
CAS Number
911222-45-2
DrugBank ID
DB11662
TTD ID
D00NZL
INTEDE ID
DR1846

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Checkpoint kinase-1 (CHK1) TTTU902 CHK1_HUMAN Modulator [3]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [4]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Substrate [4]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Pancreatic cancer
ICD Disease Classification 2C10
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Checkpoint kinase-1 (CHK1) DTT CHEK1 7.22E-191 1.43 4.74
Cytochrome P450 2D6 (CYP2D6) DME CYP2D6 1.76E-04 -4.73E-02 -2.39E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 5.59E-39 -3.76E-01 -1.64E+00
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

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2 ClinicalTrials.gov (NCT00988858) A Study of Advanced or Metastatic Non-small Cell Lung Cancer. U.S. National Institutes of Health.
3 Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Invest New Drugs. 2014 Apr;32(2):213-26.
4 Disposition and metabolism of LY2603618, a Chk-1 inhibitor following intravenous administration in patients with advanced and/or metastatic solid tumors. Xenobiotica. 2014 Sep;44(9):827-41.
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24 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
25 A phase Ib study of oral Chk1 inhibitor LY2880070 in combination with gemcitabine in patients with advanced or metastatic cancer. Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 3581-3581.
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28 Clinical pipeline report, company report or official report of AstraZeneca (2009).
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