Details of the Drug

General Information of Drug (ID: DMF3DZX)

Drug Name
CI-1040
Indication
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 478.7
Logarithm of the Partition Coefficient (xlogp) 5.6
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 5
Chemical Identifiers
Formula
C17H14ClF2IN2O2
IUPAC Name
2-(2-chloro-4-iodoanilino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide
Canonical SMILES
C1CC1CONC(=O)C2=C(C(=C(C=C2)F)F)NC3=C(C=C(C=C3)I)Cl
InChI
InChI=1S/C17H14ClF2IN2O2/c18-12-7-10(21)3-6-14(12)22-16-11(4-5-13(19)15(16)20)17(24)23-25-8-9-1-2-9/h3-7,9,22H,1-2,8H2,(H,23,24)
InChIKey
GFMMXOIFOQCCGU-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
6918454
ChEBI ID
CHEBI:91353
CAS Number
212631-79-3
DrugBank ID
DB12429
TTD ID
D0B9BU
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

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 Inhibitor [2]
Extracellular signal-regulated kinase 2 (ERK2) TT4TQBX MK01_HUMAN Inhibitor [2]
Glycogen synthase kinase-3 beta (GSK-3B) TTRSMW9 GSK3B_HUMAN Inhibitor [2]
LCK tyrosine protein kinase (LCK) TT860QF LCK_HUMAN Inhibitor [2]
MAP kinase p38 (MAPK12) TTYT93M MK12_HUMAN Inhibitor [2]
MAPK/ERK kinase kinase 1 (MAP3K1) TTQBCEJ M3K1_HUMAN Inhibitor [1]
MAPK/ERK kinase kinase 2 (MAP3K2) TTK1N5G M3K2_HUMAN Inhibitor [1]
Protein kinase C alpha (PRKCA) TTFJ8Q1 KPCA_HUMAN Inhibitor [2]
RAC-alpha serine/threonine-protein kinase (AKT1) TTWTSCV AKT1_HUMAN Inhibitor [2]
Rho-associated protein kinase 1 (ROCK1) TTZN7RP ROCK1_HUMAN Inhibitor [2]
Ribosomal protein S6 kinase beta-1 (S6K1) TTG0U4H KS6B1_HUMAN Inhibitor [2]
Serine/threonine-protein kinase Sgk1 (SGK1) TTTV8EJ SGK1_HUMAN Inhibitor [2]
Stress-activated protein kinase 2a (p38 alpha) TTQBR95 MK14_HUMAN Inhibitor [2]
Stress-activated protein kinase 2b (p38 beta) TT73U6C MK11_HUMAN Inhibitor [2]
Stress-activated protein kinase JNK1 (JNK1) TT0K6EO MK08_HUMAN Inhibitor [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Gene/Protein Processing [3]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Protein Interaction/Cellular Processes [4]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Post-Translational Modifications [5]
Caveolin-1 (CAV1) OTEZUR1L CAV1_HUMAN Gene/Protein Processing [6]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Gene/Protein Processing [7]
Cytochrome P450 3A5 (CYP3A5) OTSXFBXB CP3A5_HUMAN Gene/Protein Processing [7]
Cytochrome P450 3A7 (CYP3A7) OTTCDHHM CP3A7_HUMAN Gene/Protein Processing [7]
Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1) OT4Y9NQI MP2K1_HUMAN Gene/Protein Processing [8]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Post-Translational Modifications [9]
Interstitial collagenase (MMP1) OTI4I2V1 MMP1_HUMAN Gene/Protein Processing [10]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Discovery agent
ICD Disease Classification N.A.
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Glycogen synthase kinase-3 beta (GSK-3B) DTT GSK3B 1.26E-01 -0.23 -0.77
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
2 Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
3 ERK kinase inhibition stabilizes the aryl hydrocarbon receptor: implications for transcriptional activation and protein degradation. J Biol Chem. 2005 Feb 11;280(6):4350-9.
4 The mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibitor PD184352 (CI-1040) selectively induces apoptosis in malignant schwannoma cell lines. J Pharmacol Exp Ther. 2006 Jan;316(1):456-65. doi: 10.1124/jpet.105.091454. Epub 2005 Oct 20.
5 Anti-androgen 2-hydroxyflutamide modulates cadherin, catenin and androgen receptor phosphorylation in androgen-sensitive LNCaP and androgen-independent PC3 prostate cancer cell lines acting via PI3K/Akt and MAPK/ERK1/2 pathways. Toxicol In Vitro. 2017 Apr;40:324-335. doi: 10.1016/j.tiv.2017.01.019. Epub 2017 Feb 2.
6 Growth of hormone-dependent MCF-7 breast cancer cells is promoted by constitutive caveolin-1 whose expression is lost in an EGF-R-mediated manner during development of tamoxifen resistance. Breast Cancer Res Treat. 2010 Feb;119(3):575-91. doi: 10.1007/s10549-009-0355-8. Epub 2009 Mar 15.
7 U0126, a mitogen-activated protein kinase kinase 1 and 2 (MEK1 and 2) inhibitor, selectively up-regulates main isoforms of CYP3A subfamily via a pregnane X receptor (PXR) in HepG2 cells. Arch Toxicol. 2014 Dec;88(12):2243-59.
8 Enzyme kinetics and binding studies on inhibitors of MEK protein kinase. Biochemistry. 2008 Apr 29;47(17):5017-27. doi: 10.1021/bi701811x. Epub 2008 Apr 5.
9 Bidirectional cross talk between ERalpha and EGFR signalling pathways regulates tamoxifen-resistant growth. Breast Cancer Res Treat. 2006 Mar;96(2):131-46. doi: 10.1007/s10549-005-9070-2. Epub 2005 Oct 27.
10 Cigarette smoke components induce matrix metalloproteinase-1 in aortic endothelial cells through inhibition of mTOR signaling. Toxicol Sci. 2011 Oct;123(2):542-9. doi: 10.1093/toxsci/kfr181. Epub 2011 Jul 8.