Details of the Drug

General Information of Drug (ID: DMW50NF)

Drug Name
LE-SN38
Synonyms
7-Ethyl-10-hydroxycamptothecin; 86639-52-3; SN-38; SN 38 lactone; 7-Ethyl-10-hydroxy-camptothecin; SN 38; 10-Hydroxy-7-ethylcamptothecin; 7-Ethyl-10-hydroxycamptothecine; SN38; 7-Ethyl-10-hydroxy-20(S)-camptothecin; UNII-0H43101T0J; Captothecin, 7-ethyl-10-hydroxy-; CHEBI:8988; (S)-4,11-Diethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; 7-Ethyl-10-hydroxy camptothecin; NSC673596; 0H43101T0J; (+)-7-ETHYL-10-HYDROXYCAMPTOTHECIN; 113015-38-6
Indication
Disease Entry ICD 11 Status REF
Colorectal cancer 2B91.Z Phase 2 [1]
Solid tumour/cancer 2A00-2F9Z Phase 2 [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 392.4
Logarithm of the Partition Coefficient (xlogp) 1.4
Rotatable Bond Count (rotbonds) 2
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 6
Chemical Identifiers
Formula
C22H20N2O5
IUPAC Name
(19S)-10,19-diethyl-7,19-dihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-14,18-dione
Canonical SMILES
CCC1=C2CN3C(=CC4=C(C3=O)COC(=O)[C@@]4(CC)O)C2=NC5=C1C=C(C=C5)O
InChI
InChI=1S/C22H20N2O5/c1-3-12-13-7-11(25)5-6-17(13)23-19-14(12)9-24-18(19)8-16-15(20(24)26)10-29-21(27)22(16,28)4-2/h5-8,25,28H,3-4,9-10H2,1-2H3/t22-/m0/s1
InChIKey
FJHBVJOVLFPMQE-QFIPXVFZSA-N
Cross-matching ID
PubChem CID
104842
ChEBI ID
CHEBI:8988
CAS Number
86639-52-3
DrugBank ID
DB05482
TTD ID
D0B6YB
VARIDT ID
DR00161
INTEDE ID
DR0024
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
DNA topoisomerase I (TOP1) TTGTQHC TOP1_HUMAN Inhibitor [3]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [4]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [5]
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [6]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [7]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [8]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [9]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Substrate [10]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Substrate [11]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Colorectal cancer
ICD Disease Classification 2B91.Z
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
DNA topoisomerase I (TOP1) DTT TOP1 6.65E-01 0.2 0.39
Multidrug resistance-associated protein 1 (ABCC1) DTP MRP1 1.90E-30 1.76E-01 7.31E-01
Breast cancer resistance protein (ABCG2) DTP BCRP 3.87E-47 -1.28E+00 -1.63E+00
Multidrug resistance-associated protein 2 (ABCC2) DTP MRP2 1.02E-08 -5.12E-02 -2.22E-01
Multidrug resistance-associated protein 4 (ABCC4) DTP MRP4 1.26E-03 -4.35E-01 -5.28E-01
Organic anion transporting polypeptide 1B3 (SLCO1B3) DTP OATP1B3 3.46E-61 1.83E-01 7.90E-01
Organic anion transporting polypeptide 1B1 (SLCO1B1) DTP OATP1B1 2.80E-34 1.44E-01 9.71E-01
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME UGT1A1 2.33E-02 1.75E-02 8.91E-02
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Randomized phase 2 study of pegylated SN-38 (EZN-2208) or irinotecan plus cetuximab in patients with advanced colorectal cancer. Cancer. 2013 Dec 15;119(24):4223-30.
2 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. (Ligand id: 6925).
3 Analysis of type of cell death induced by topoisomerase inhibitor SN-38 in human oral squamous cell carcinoma cell lines. Anticancer Res. 2012 Nov;32(11):4823-32.
4 Biliary excretion mechanism of CPT-11 and its metabolites in humans: involvement of primary active transporters. Cancer Res. 1998 Nov 15;58(22):5137-43.
5 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
6 ATP-Dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P. Mol Pharmacol. 1999 May;55(5):921-8.
7 Transport of 7-ethyl-10-hydroxycamptothecin (SN-38) by breast cancer resistance protein ABCG2 in human lung cancer cells. Biochem Biophys Res Commun. 2001 Nov 9;288(4):827-32.
8 Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
9 Rapid screening of antineoplastic candidates for the human organic anion transporter OATP1B3 substrates using fluorescent probes. Cancer Lett. 2008 Feb 18;260(1-2):163-9.
10 Effects of green tea compounds on irinotecan metabolism. Drug Metab Dispos. 2007 Feb;35(2):228-33.
11 Correlation between plasma concentration ratios of SN-38 glucuronide and SN-38 and neutropenia induction in patients with colorectal cancer and wild-type UGT1A1 gene. Oncol Lett. 2012 Mar;3(3):694-698.