Details of the Drug

General Information of Drug (ID: DMCRGY4)

Drug Name
Karenitecin
Synonyms Karenitecin (TN)
Indication
Disease Entry ICD 11 Status REF
Lung cancer 2C25.0 Phase 3 [1]
Ovarian cancer 2C73 Phase 3 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski):
0		 Molecular Weight 448.6
Logarithm of the Partition Coefficient Not Available
Rotatable Bond Count 4
Hydrogen Bond Donor Count 1
Hydrogen Bond Acceptor Count 5
Chemical Identifiers
Formula
C25H28N2O4Si
IUPAC Name
(19S)-19-ethyl-19-hydroxy-10-(2-trimethylsilylethyl)-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione
Canonical SMILES
CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=C(C5=CC=CC=C5N=C4C3=C2)CC[Si](C)(C)C)O
InChI
InChI=1S/C25H28N2O4Si/c1-5-25(30)19-12-21-22-17(13-27(21)23(28)18(19)14-31-24(25)29)15(10-11-32(2,3)4)16-8-6-7-9-20(16)26-22/h6-9,12,30H,5,10-11,13-14H2,1-4H3/t25-/m0/s1
InChIKey
POADTFBBIXOWFJ-VWLOTQADSA-N
Cross-matching ID
PubChem CID
148202
CAS Number
203923-89-1
UNII
24R60NVC41
DrugBank ID
DB05806
TTD ID
D02CZK
VARIDT ID
DR01349
INTEDE ID
DR1901
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
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Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
DNA topoisomerase (TOP) TT2GPK3 NOUNIPROTAC Inhibitor [2]
DNA topoisomerase I (TOP1) TTGTQHC TOP1_HUMAN Inhibitor [3]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [4]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [6]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Substrate [6]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Substrate [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

ICD Disease Classification 02 Neoplasm
Disease Class ICD-11: 2C82 Prostate cancer
The Studied Tissue Lung tissue
The Studied Disease Lung cancer [ICD-11:2C82]
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
Breast cancer resistance protein (ABCG2) DTP BCRP 3.87E-47 -1.28E+00 -1.63E+00
Organic anion transporting polypeptide 1B1 (SLCO1B1) DTP OATP1B1 2.80E-34 1.44E-01 9.71E-01
Cytochrome P450 2C8 (CYP2C8) DME CYP2C8 5.28E-05 1.90E-02 1.09E-01
Cytochrome P450 2D6 (CYP2D6) DME CYP2D6 1.76E-04 -4.73E-02 -2.39E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 5.59E-39 -3.76E-01 -1.64E+00
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 ClinicalTrials.gov (NCT00477282) Karenitecin Versus Topotecan in Patients With Advanced Epithelial Ovarian Cancer. U.S. National Institutes of Health.
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 Characterization of protein kinase chk1 essential for the cell cycle checkpoint after exposure of human head and neck carcinoma A253 cells to a novel topoisomerase I inhibitor BNP1350. Mol Pharmacol.2000 Mar;57(3):453-9.
4 Pharmacogenomic importance of ABCG2. Pharmacogenomics. 2008 Aug;9(8):1005-9.
5 Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
6 Evaluation of in vitro drug interactions with karenitecin, a novel, highly lipophilic camptothecin derivative in phase II clinical development. J Clin Pharmacol. 2003 Sep;43(9):1008-14.