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
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
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 (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.