Details of the Drug

General Information of Drug (ID: DM8K5IF)

Drug Name
E7850
Synonyms Irofulven
Indication
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 2 [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 246.3
Topological Polar Surface Area (xlogp) -0.2
Rotatable Bond Count (rotbonds) 1
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 3
ADMET Property
Clearance
The drug present in the plasma can be removed from the body at the rate of 140 mL/min/kg [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 0.3 hours [3]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 3.1 L/kg [3]
Chemical Identifiers
Formula
C15H18O3
IUPAC Name
(5'R)-5'-hydroxy-1'-(hydroxymethyl)-2',5',7'-trimethylspiro[cyclopropane-1,6'-indene]-4'-one
Canonical SMILES
CC1=C(C2=C(C3(CC3)[C@@](C(=O)C2=C1)(C)O)C)CO
InChI
InChI=1S/C15H18O3/c1-8-6-10-12(11(8)7-16)9(2)15(4-5-15)14(3,18)13(10)17/h6,16,18H,4-5,7H2,1-3H3/t14-/m0/s1
InChIKey
NICJCIQSJJKZAH-AWEZNQCLSA-N
Cross-matching ID
PubChem CID
148189
ChEBI ID
CHEBI:135002
CAS Number
158440-71-2
DrugBank ID
DB05786
TTD ID
D00EPT

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Serine/threonine-protein kinase Chk2 (RAD53) TT9ABMF CHK2_HUMAN Modulator [4]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 Irofulven induces replication-dependent CHK2 activation related to p53 status. Biochem Pharmacol. 2007 Feb 15;73(4):469-80.
2 ATM-dependent CHK2 activation induced by anticancer agent, irofulven. J Biol Chem. 2004 Sep 17;279(38):39584-92.
3 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1988).
5 Ribosomal S6 kinase (RSK) modulators: a patent review.Expert Opin Ther Pat. 2016 Sep;26(9):1061-78.
6 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
7 Discovery of an orally efficacious inhibitor of anaplastic lymphoma kinase. J Med Chem. 2012 May 24;55(10):4580-93.
8 Potent inhibition of checkpoint kinase activity by a hymenialdisine-derived indoloazepine. Bioorg Med Chem Lett. 2004 Aug 16;14(16):4319-21.
9 Checkpoint kinase inhibitors: SAR and radioprotective properties of a series of 2-arylbenzimidazoles. J Med Chem. 2005 Mar 24;48(6):1873-85.
10 Cellular inhibition of checkpoint kinase 2 (Chk2) and potentiation of camptothecins and radiation by the novel Chk2 inhibitor PV1019 [7-nitro-1H-indole-2-carboxylic acid {4-[1-(guanidinohydrazone)-ethyl]-phenyl}-amide]. J Pharmacol Exp Ther. 2009 Dec;331(3):816-26.
11 CCT241533 Is a Potent and Selective Inhibitor of CHK2 that Potentiates the Cytotoxicity of PARP Inhibitors. Cancer Res. 2011 Jan 15;71(2):463-72.
12 A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8.