Details of the Drug-Related molecule(s) Expression Atlas

General Information of Drug (ID: DMW50NF)

Drug Name
LE-SN38 Drug Info
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]
Cross-matching ID
PubChem CID
104842
ChEBI ID
CHEBI:8988
CAS Number
CAS 86639-52-3
TTD Drug ID
DMW50NF
VARIDT Drug ID
DR00161
INTEDE Drug ID
DR0024

Molecule(s) Related to 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 Highest Status REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Phase 2 [4]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Phase 2 [5]
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Phase 2 [6]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Phase 2 [7]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Phase 2 [8]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Phase 2 [9]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID Highest Status REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Phase 2 [10]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Phase 2 [11]

The Expression Level of Molecule(s) in Normal Tissue of Major ADME-Related Organs

Molecule Molecule Type Gene Name Liver Colon Kidney Small Intestine
Multidrug resistance-associated protein 1 (ABCC1) DTP MRP1 4.838 6.296 5.935 6.146
Breast cancer resistance protein (ABCG2) DTP BCRP 6.732 7.513 6.326 9.277
Multidrug resistance-associated protein 2 (ABCC2) DTP MRP2 7.751 4.17 6.425 6.282
Multidrug resistance-associated protein 4 (ABCC4) DTP MRP4 4.797 7.054 6.875 5.42
Organic anion transporting polypeptide 1B3 (SLCO1B3) DTP OATP1B3 8.873 2.17 2.485 3.322
Organic anion transporting polypeptide 1B1 (SLCO1B1) DTP OATP1B1 9.79 0.485 3.511 2.07
Molecule Expression Atlas in Normal Tissue of Major ADME-related organs

The Expression Level of Molecule(s) between Disease Section and Healthy Individual Tissue

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 between Disease Section and Healthy Individual Tissue

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.