NAV

SN-38

Identification

Generic Name
SN-38
DrugBank Accession Number
DB05482
Background

7-ethyl-10-hydroxycamptothecin (SN 38) is a liposomal formulation of the active metabolite of Irinotecan Irinotecan, a chemotherapeutic pro-drug approved for the treatment of advanced colorectal cancer. SN 38 has been used in trials studying the treatment of Cancer, Advanced Solid Tumors, Small Cell Lung Cancer, Metastatic Colorectal Cancer, and Triple Negative Breast Cancer, among others.

Type
Small Molecule
Groups
Investigational
Structure
3D
Similar Structures
Weight
Average: 392.4046
Monoisotopic: 392.13722176
Chemical Formula
C22H20N2O5
Synonyms
  • 1H-PYRANO(3',4':6,7)INDOLIZINO(1,2-B)QUINOLINE-3,14(4H,12H)-DIONE, 4,11-DIETHYL-4,9-DIHYDROXY-, (4S)-
  • IRINOTECAN RELATED COMPOUND B
External IDs
  • LE-SN38
  • NK 012
  • NK-012
  • NK012
  • SN 38
  • SN-38
  • SN38
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Pharmacology

Indication

Investigated for use/treatment in colorectal cancer.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

SN-38 (7-ethyl-10-hydroxycamptothecin) is the active metabolite of Irinotecan (CPT-11). Irinotecan is a topoisomerase I inhibitor commercially available as Camptosar®. SN-38 has been found to be 200–2000 times more cytotoxic than CPT-11, but has not been used as an anticancer drug due to its poor solubility in pharmaceutically acceptable solvents and low affinity to lipid membranes. SN-38 also undergoes a reversible conversion to an inactive open lactone ring structure at physiological pH. LE-SN-38 is a novel lipsome based formulation containing liposomes of uniform size distribution (<200 nm). Drug entrapment efficiency of the formulation is>95%.

Mechanism of action

The entrapment of SN-38 in lipsomes results in a more stable and more soluble form of the drug. This allows for increased affinity of SN-38 to lipid membranes and improved delivery of the drug to tumor sites. SN-38 is a highly effective cytotoxic topoisomerase I inhibitor.

TargetActionsOrganism
UDNA topoisomerase 1Not AvailableHumans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
PathwayCategory
Irinotecan Metabolism PathwayDrug metabolism
Irinotecan Action PathwayDrug action
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
Integrate drug-drug
interactions in your software
AbametapirThe serum concentration of 7-ethyl-10-hydroxycamptothecin can be increased when it is combined with Abametapir.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with 7-ethyl-10-hydroxycamptothecin.
AcalabrutinibThe serum concentration of Acalabrutinib can be increased when it is combined with 7-ethyl-10-hydroxycamptothecin.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with 7-ethyl-10-hydroxycamptothecin.
AlbendazoleThe metabolism of Albendazole can be decreased when combined with 7-ethyl-10-hydroxycamptothecin.
Food Interactions
Not Available

Products

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International/Other Brands
NeoLipid Camptosar

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as camptothecins. These are heterocyclic compounds comprising a planar pentacyclic ring structure, that includes a pyrrolo[3,4-beta]-quinoline moiety (rings A, B and C), conjugated pyridone moiety (ring D) and one chiral center at position 20 within the alpha-hydroxy lactone ring with (S) configuration (the E-ring).
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Camptothecins
Sub Class
Not Available
Direct Parent
Camptothecins
Alternative Parents
Hydroxyquinolines / Pyranopyridines / Pyridinones / 1-hydroxy-2-unsubstituted benzenoids / Tertiary alcohols / Heteroaromatic compounds / Carboxylic acid esters / Lactams / Lactones / Azacyclic compounds
show 7 more
Substituents
1-hydroxy-2-unsubstituted benzenoid / Alcohol / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Camptothecin / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Heteroaromatic compound
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
pyranoindolizinoquinoline (CHEBI:8988)
Affected organisms
Not Available

Chemical Identifiers

UNII
0H43101T0J
CAS number
86639-52-3
InChI Key
FJHBVJOVLFPMQE-QFIPXVFZSA-N
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
IUPAC Name
(19S)-10,19-diethyl-7,19-dihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.0^{2,11}.0^{4,9}.0^{15,20}]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaene-14,18-dione
SMILES
CCC1=C2C=C(O)C=CC2=NC2=C1CN1C2=CC2=C(COC(=O)[C@]2(O)CC)C1=O

References

General References
  1. Xuan T, Zhang JA, Ahmad I: HPLC method for determination of SN-38 content and SN-38 entrapment efficiency in a novel liposome-based formulation, LE-SN38. J Pharm Biomed Anal. 2006 May 3;41(2):582-8. Epub 2006 Jan 18. [Article]
  2. Peikov V, Ugwu S, Parmar M, Zhang A, Ahmad I: pH-dependent association of SN-38 with lipid bilayers of a novel liposomal formulation. Int J Pharm. 2005 Aug 11;299(1-2):92-9. [Article]
  3. Pal A, Khan S, Wang YF, Kamath N, Sarkar AK, Ahmad A, Sheikh S, Ali S, Carbonaro D, Zhang A, Ahmad I: Preclinical safety, pharmacokinetics and antitumor efficacy profile of liposome-entrapped SN-38 formulation. Anticancer Res. 2005 Jan-Feb;25(1A):331-41. [Article]
  4. Khan S, Ahmad A, Guo W, Wang YF, Abu-Qare A, Ahmad I: A simple and sensitive LC/MS/MS assay for 7-ethyl-10-hydroxycamptothecin (SN-38) in mouse plasma and tissues: application to pharmacokinetic study of liposome entrapped SN-38 (LE-SN38). J Pharm Biomed Anal. 2005 Feb 7;37(1):135-42. [Article]
  5. Lei S, Chien PY, Sheikh S, Zhang A, Ali S, Ahmad I: Enhanced therapeutic efficacy of a novel liposome-based formulation of SN-38 against human tumor models in SCID mice. Anticancer Drugs. 2004 Sep;15(8):773-8. [Article]
  6. Zhang JA, Xuan T, Parmar M, Ma L, Ugwu S, Ali S, Ahmad I: Development and characterization of a novel liposome-based formulation of SN-38. Int J Pharm. 2004 Feb 11;270(1-2):93-107. [Article]
  7. Khan S, Ahmad A, Ahmad I: A sensitive and rapid liquid chromatography tandem mass spectrometry method for quantitative determination of 7-ethyl-10-hydroxycamptothecin (SN-38) in human plasma containing liposome-based SN-38 (LE-SN38). Biomed Chromatogr. 2003 Dec;17(8):493-9. [Article]
  8. Guo W, Ahmad A, Khan S, Dahhani F, Wang YF, Ahmad I: Determination by liquid chromatography with fluorescence detection of total 7-ethyl-10-hydroxy-camptothecin (SN-38) in beagle dog plasma after intravenous administration of liposome-based SN-38 (LE-SN38). J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jul 5;791(1-2):85-92. [Article]
Human Metabolome Database
HMDB0060510
KEGG Compound
C11173
PubChem Compound
104842
PubChem Substance
175427017
ChemSpider
94634
BindingDB
50418088
ChEBI
8988
ChEMBL
CHEMBL837
ZINC
ZINC000004099013
PDBe Ligand
RS4
Wikipedia
SN-38
PDB Entries
6vxj

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
2CompletedTreatmentColorectal Cancer1
2CompletedTreatmentSmall Cell Lung Cancer (SCLC)1
2CompletedTreatmentTriple-Negative Breast Cancer1
2Not Yet RecruitingTreatmentLocally Advanced Cholangiocarcinoma / Metastatic Cholangiocarcinoma / Recurrent Cholangiocarcinoma / Stage III Hilar Cholangiocarcinoma AJCC v8 / Stage III Intrahepatic Cholangiocarcinoma AJCC v8 / Stage IV Hilar Cholangiocarcinoma AJCC v8 / Stage IV Intrahepatic Cholangiocarcinoma AJCC v81
2RecruitingTreatmentPlatinum drug resistant Fallopian tube cancer / Platinum-Resistant Ovarian Carcinoma / Platinum-Resistant Primary Peritoneal Carcinoma / Stage IV Fallopian Tube Cancer AJCC v8 / Stage IV Ovarian Cancer AJCC v8 / Stage IV Primary Peritoneal Cancer AJCC v81

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.29 mg/mLALOGPS
logP2.73ALOGPS
logP1.87Chemaxon
logS-3.1ALOGPS
pKa (Strongest Acidic)9.66Chemaxon
pKa (Strongest Basic)3.92Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area99.96 Å2Chemaxon
Rotatable Bond Count2Chemaxon
Refractivity106.12 m3·mol-1Chemaxon
Polarizability41.43 Å3Chemaxon
Number of Rings5Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.6456
Blood Brain Barrier-0.8359
Caco-2 permeable-0.8956
P-glycoprotein substrateSubstrate0.7357
P-glycoprotein inhibitor INon-inhibitor0.8184
P-glycoprotein inhibitor IINon-inhibitor0.9399
Renal organic cation transporterNon-inhibitor0.8729
CYP450 2C9 substrateNon-substrate0.883
CYP450 2D6 substrateNon-substrate0.8538
CYP450 3A4 substrateSubstrate0.6092
CYP450 1A2 substrateInhibitor0.7118
CYP450 2C9 inhibitorNon-inhibitor0.863
CYP450 2D6 inhibitorNon-inhibitor0.9305
CYP450 2C19 inhibitorNon-inhibitor0.8155
CYP450 3A4 inhibitorInhibitor0.6952
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5726
Ames testNon AMES toxic0.5766
CarcinogenicityNon-carcinogens0.7761
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.1600 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9953
hERG inhibition (predictor II)Non-inhibitor0.7325
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0cds-0019000000-79b6acd0ac5020e4fdae
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-0009000000-f747ef36c16162600185
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-0009000000-7ac8342ec37a27c6e40e
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-004l-0009000000-be8168da1f458e558632
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-01ow-0009000000-adc39d66c6a3ecd79181
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-052f-0179000000-d26ce7617c56760b58e5
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0btc-0129000000-dc75038bb766fac0878d
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-0009000000-f747ef36c16162600185
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-0009000000-7ac8342ec37a27c6e40e
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-004l-0009000000-be8168da1f458e558632
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-01ow-0009000000-adc39d66c6a3ecd79181
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-052f-0179000000-d26ce7617c56760b58e5
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0btc-0129000000-dc75038bb766fac0878d
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-209.6817999
predicted
DarkChem Lite v0.1.0
[M-H]-210.6378999
predicted
DarkChem Lite v0.1.0
[M-H]-184.57295
predicted
DeepCCS 1.0 (2019)
[M-H]-209.6817999
predicted
DarkChem Lite v0.1.0
[M-H]-210.6378999
predicted
DarkChem Lite v0.1.0
[M-H]-184.57295
predicted
DeepCCS 1.0 (2019)
[M+H]+210.4055999
predicted
DarkChem Lite v0.1.0
[M+H]+211.3199999
predicted
DarkChem Lite v0.1.0
[M+H]+186.93095
predicted
DeepCCS 1.0 (2019)
[M+H]+210.4055999
predicted
DarkChem Lite v0.1.0
[M+H]+211.3199999
predicted
DarkChem Lite v0.1.0
[M+H]+186.93095
predicted
DeepCCS 1.0 (2019)
[M+Na]+210.4791999
predicted
DarkChem Lite v0.1.0
[M+Na]+210.8792999
predicted
DarkChem Lite v0.1.0
[M+Na]+193.84593
predicted
DeepCCS 1.0 (2019)
[M+Na]+210.4791999
predicted
DarkChem Lite v0.1.0
[M+Na]+210.8792999
predicted
DarkChem Lite v0.1.0
[M+Na]+193.84593
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Details1. DNA topoisomerase 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Poly(a) rna binding
Specific Function
Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a singl...
Gene Name
TOP1
Uniprot ID
P11387
Uniprot Name
DNA topoisomerase 1
Molecular Weight
90725.19 Da

Enzymes

Details1. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Hanioka N, Ozawa S, Jinno H, Tanaka-Kagawa T, Nishimura T, Ando M, Sawada Ji J: Interaction of irinotecan (CPT-11) and its active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38) with human cytochrome P450 enzymes. Drug Metab Dispos. 2002 Apr;30(4):391-6. [Article]
  2. Mirkov S, Komoroski BJ, Ramirez J, Graber AY, Ratain MJ, Strom SC, Innocenti F: Effects of green tea compounds on irinotecan metabolism. Drug Metab Dispos. 2007 Feb;35(2):228-33. doi: 10.1124/dmd.106.012047. Epub 2006 Nov 15. [Article]
  3. Camptosar FDA label [File]

Drug created at November 18, 2007 18:25 / Updated at September 28, 2023 05:40