Target Information
| Target General Information | Top | |||||
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| Target ID |
T09826
(Former ID: TTDNC00422)
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| Target Name |
DNA topoisomerase I (TOP1)
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| Synonyms |
DNA topoisomerase I
Click to Show/Hide
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| Gene Name |
TOP1
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 5 Target-related Diseases | + | ||||
| 1 | Bacterial infection [ICD-11: 1A00-1C4Z] | |||||
| 2 | Colorectal cancer [ICD-11: 2B91] | |||||
| 3 | Lung cancer [ICD-11: 2C25] | |||||
| 4 | Ovarian cancer [ICD-11: 2C73] | |||||
| 5 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
| Function |
Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then rotates around the intact phosphodiester bond on the opposing strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component ARNTL/BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the ARNTL/BMAL1 promoter. 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.
Click to Show/Hide
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| BioChemical Class |
Topoisomerase
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| UniProt ID | ||||||
| EC Number |
EC 5.6.2.2
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| Sequence |
MSGDHLHNDSQIEADFRLNDSHKHKDKHKDREHRHKEHKKEKDREKSKHSNSEHKDSEKK
HKEKEKTKHKDGSSEKHKDKHKDRDKEKRKEEKVRASGDAKIKKEKENGFSSPPQIKDEP EDDGYFVPPKEDIKPLKRPRDEDDADYKPKKIKTEDTKKEKKRKLEEEEDGKLKKPKNKD KDKKVPEPDNKKKKPKKEEEQKWKWWEEERYPEGIKWKFLEHKGPVFAPPYEPLPENVKF YYDGKVMKLSPKAEEVATFFAKMLDHEYTTKEIFRKNFFKDWRKEMTNEEKNIITNLSKC DFTQMSQYFKAQTEARKQMSKEEKLKIKEENEKLLKEYGFCIMDNHKERIANFKIEPPGL FRGRGNHPKMGMLKRRIMPEDIIINCSKDAKVPSPPPGHKWKEVRHDNKVTWLVSWTENI QGSIKYIMLNPSSRIKGEKDWQKYETARRLKKCVDKIRNQYREDWKSKEMKVRQRAVALY FIDKLALRAGNEKEEGETADTVGCCSLRVEHINLHPELDGQEYVVEFDFLGKDSIRYYNK VPVEKRVFKNLQLFMENKQPEDDLFDRLNTGILNKHLQDLMEGLTAKVFRTYNASITLQQ QLKELTAPDENIPAKILSYNRANRAVAILCNHQRAPPKTFEKSMMNLQTKIDAKKEQLAD ARRDLKSAKADAKVMKDAKTKKVVESKKKAVQRLEEQLMKLEVQATDREENKQIALGTSK LNYLDPRITVAWCKKWGVPIEKIYNKTQREKFAWAIDMADEDYEF Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| ADReCS ID | BADD_A01146 ; BADD_A05675 | |||||
| HIT2.0 ID | T99XQ3 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 4 Approved Drugs | + | ||||
| 1 | B-Lactams | Drug Info | Approved | Bacterial infection | [3] | |
| 2 | Belotecan hydrocholoride | Drug Info | Approved | Small-cell lung cancer | [4] | |
| 3 | Irinotecan | Drug Info | Approved | Colorectal cancer | [5], [6] | |
| 4 | Topotecan | Drug Info | Approved | Ovarian cancer | [7], [8] | |
| Clinical Trial Drug(s) | [+] 31 Clinical Trial Drugs | + | ||||
| 1 | Camptothecin | Drug Info | Phase 3 | Solid tumour/cancer | [11] | |
| 2 | Edotecarin | Drug Info | Phase 3 | Gastric adenocarcinoma | [12] | |
| 3 | Etirinotecan pegol | Drug Info | Phase 3 | Breast cancer | [13] | |
| 4 | Exatecan | Drug Info | Phase 3 | Solid tumour/cancer | [14] | |
| 5 | Karenitecin | Drug Info | Phase 3 | Lung cancer | [15] | |
| 6 | 9-AMINOCAMPTOTHECIN | Drug Info | Phase 2 | Acquired immune deficiency syndrome | [19] | |
| 7 | AR-67 | Drug Info | Phase 2 | Myelodysplastic syndrome | [20] | |
| 8 | CRLX101 | Drug Info | Phase 2 | Solid tumour/cancer | [21] | |
| 9 | DIFLOMOTECAN | Drug Info | Phase 2 | Solid tumour/cancer | [22] | |
| 10 | EQ-917 | Drug Info | Phase 2 | Solid tumour/cancer | [23] | |
| 11 | Gimatecan | Drug Info | Phase 2 | Breast cancer | [24] | |
| 12 | LE-SN38 | Drug Info | Phase 2 | Solid tumour/cancer | [25], [26] | |
| 13 | PEG-SN38 | Drug Info | Phase 2 | Metastatic colorectal cancer | [26], [27] | |
| 14 | Pegamotecan | Drug Info | Phase 2 | Esophageal cancer | [28] | |
| 15 | Polyglutamate camptothecin | Drug Info | Phase 2 | Solid tumour/cancer | [29] | |
| 16 | TLC-388 | Drug Info | Phase 2 | Solid tumour/cancer | [30] | |
| 17 | XR-5000 | Drug Info | Phase 2 | Colorectal cancer | [31] | |
| 18 | PEN-866 | Drug Info | Phase 1/2 | Solid tumour/cancer | [33] | |
| 19 | ABI-011 | Drug Info | Phase 1 | Solid tumour/cancer | [41] | |
| 20 | Afeletecan | Drug Info | Phase 1 | Breast cancer | [42] | |
| 21 | Daniquidone | Drug Info | Phase 1 | Lymphoma | [43] | |
| 22 | DFP 13318 | Drug Info | Phase 1 | Solid tumour/cancer | [33] | |
| 23 | DRF-1042 | Drug Info | Phase 1 | Solid tumour/cancer | [44] | |
| 24 | ELOMOTECAN HYDROCHLORIDE | Drug Info | Phase 1 | Solid tumour/cancer | [45] | |
| 25 | Genz-644282 | Drug Info | Phase 1 | Solid tumour/cancer | [46] | |
| 26 | GZ402674 | Drug Info | Phase 1 | Solid tumour/cancer | [47] | |
| 27 | INTOPLICINE | Drug Info | Phase 1 | Solid tumour/cancer | [48] | |
| 28 | IT-141 | Drug Info | Phase 1 | Solid tumour/cancer | [33] | |
| 29 | Namitecan | Drug Info | Phase 1 | Solid tumour/cancer | [49] | |
| 30 | Tafluposide | Drug Info | Phase 1 | Solid tumour/cancer | [50] | |
| 31 | (S)-DRF-1042 | Drug Info | Clinical trial | Bladder cancer | [51] | |
| Discontinued Drug(s) | [+] 13 Discontinued Drugs | + | ||||
| 1 | BECATECARIN | Drug Info | Discontinued in Phase 3 | Solid tumour/cancer | [52] | |
| 2 | Atiratecan | Drug Info | Discontinued in Phase 2 | Colorectal cancer | [53] | |
| 3 | Lurtotecan | Drug Info | Discontinued in Phase 2 | Ovarian cancer | [54] | |
| 4 | NK-611 | Drug Info | Discontinued in Phase 2 | Solid tumour/cancer | [55] | |
| 5 | S-16020-2 | Drug Info | Discontinued in Phase 2 | Solid tumour/cancer | [56] | |
| 6 | DE-310 | Drug Info | Discontinued in Phase 1 | Solid tumour/cancer | [57] | |
| 7 | BE-13793C | Drug Info | Terminated | Solid tumour/cancer | [58] | |
| 8 | BN-80245 | Drug Info | Terminated | Solid tumour/cancer | [59] | |
| 9 | CZ-112 | Drug Info | Terminated | Solid tumour/cancer | [60] | |
| 10 | Datelliptium chloride | Drug Info | Terminated | Breast cancer | [61] | |
| 11 | ED-110 | Drug Info | Terminated | Solid tumour/cancer | [62] | |
| 12 | PIROXANTRONE | Drug Info | Terminated | Solid tumour/cancer | [63] | |
| 13 | TAN-1496 | Drug Info | Terminated | Solid tumour/cancer | [64] | |
| Mode of Action | [+] 6 Modes of Action | + | ||||
| Inhibitor | [+] 51 Inhibitor drugs | + | ||||
| 1 | B-Lactams | Drug Info | [65] | |||
| 2 | Edotecarin | Drug Info | [12] | |||
| 3 | Etirinotecan pegol | Drug Info | [70] | |||
| 4 | Exatecan | Drug Info | [71] | |||
| 5 | Karenitecin | Drug Info | [72] | |||
| 6 | 9-AMINOCAMPTOTHECIN | Drug Info | [73] | |||
| 7 | AR-67 | Drug Info | [74] | |||
| 8 | DIFLOMOTECAN | Drug Info | [76] | |||
| 9 | EQ-917 | Drug Info | [77] | |||
| 10 | Gimatecan | Drug Info | [78] | |||
| 11 | LE-SN38 | Drug Info | [79], [80] | |||
| 12 | PEG-SN38 | Drug Info | [81] | |||
| 13 | Pegamotecan | Drug Info | [82] | |||
| 14 | Polyglutamate camptothecin | Drug Info | [11] | |||
| 15 | TLC-388 | Drug Info | [30] | |||
| 16 | PEN-866 | Drug Info | [33] | |||
| 17 | Afeletecan | Drug Info | [84] | |||
| 18 | DFP 13318 | Drug Info | [33] | |||
| 19 | DRF-1042 | Drug Info | [73], [86] | |||
| 20 | Genz-644282 | Drug Info | [89] | |||
| 21 | IT-141 | Drug Info | [33] | |||
| 22 | Namitecan | Drug Info | [92] | |||
| 23 | (S)-DRF-1042 | Drug Info | [90] | |||
| 24 | Atiratecan | Drug Info | [95] | |||
| 25 | Lurtotecan | Drug Info | [90], [96] | |||
| 26 | NK-611 | Drug Info | [97] | |||
| 27 | DE-310 | Drug Info | [99] | |||
| 28 | BN-80245 | Drug Info | [101] | |||
| 29 | CZ-112 | Drug Info | [102] | |||
| 30 | (5Z,9Z)-5,9-heptacosadienoic acid | Drug Info | [108] | |||
| 31 | 10-hydroxycamptothecin | Drug Info | [109] | |||
| 32 | 3,3'-(4-phenylpyridine-2,6-diyl)diphenol | Drug Info | [111] | |||
| 33 | 3-(4-phenyl-2,4'-bipyridin-6-yl)phenol | Drug Info | [111] | |||
| 34 | 3-(4-phenyl-6-(thiophen-2-yl)pyridin-2-yl)-phenol | Drug Info | [111] | |||
| 35 | 3-(4-phenyl-6-(thiophen-3-yl)pyridin-2-yl)-phenol | Drug Info | [111] | |||
| 36 | 3-(6-phenyl-2,4'-bipyridin-4-yl)phenol | Drug Info | [111] | |||
| 37 | 4-(4,6-diphenylpyridin-2-yl)phenol | Drug Info | [111] | |||
| 38 | 4-(6-phenyl-2,4'-bipyridin-4-yl)phenol | Drug Info | [111] | |||
| 39 | 4-hydroxysaprothoquinone | Drug Info | [112] | |||
| 40 | A35566-A | Drug Info | [90] | |||
| 41 | ATI-1150 | Drug Info | [90] | |||
| 42 | CHO793076 | Drug Info | [114] | |||
| 43 | DTS-108 | Drug Info | [90] | |||
| 44 | E-758 | Drug Info | [116] | |||
| 45 | Homocamptothecins (hCPTs) | Drug Info | [117] | |||
| 46 | IDN-5174 | Drug Info | [90] | |||
| 47 | IDN-6384 | Drug Info | [90] | |||
| 48 | MEN-14295 | Drug Info | [90] | |||
| 49 | NSC-341622 | Drug Info | [120] | |||
| 50 | ROSETTACIN | Drug Info | [120] | |||
| 51 | TOPOSTATIN | Drug Info | [121] | |||
| Modulator | [+] 21 Modulator drugs | + | ||||
| 1 | Belotecan hydrocholoride | Drug Info | [66], [67] | |||
| 2 | Irinotecan | Drug Info | [68] | |||
| 3 | Topotecan | Drug Info | [68] | |||
| 4 | Camptothecin | Drug Info | [11], [69] | |||
| 5 | CRLX101 | Drug Info | [75] | |||
| 6 | XR-5000 | Drug Info | [31] | |||
| 7 | ABI-011 | Drug Info | [83] | |||
| 8 | Daniquidone | Drug Info | [85] | |||
| 9 | ELOMOTECAN HYDROCHLORIDE | Drug Info | [87], [88] | |||
| 10 | GZ402674 | Drug Info | [90] | |||
| 11 | INTOPLICINE | Drug Info | [91] | |||
| 12 | Tafluposide | Drug Info | [93] | |||
| 13 | BECATECARIN | Drug Info | [94] | |||
| 14 | S-16020-2 | Drug Info | [98] | |||
| 15 | BE-13793C | Drug Info | [100] | |||
| 16 | Datelliptium chloride | Drug Info | [103] | |||
| 17 | ED-110 | Drug Info | [104], [105] | |||
| 18 | PIROXANTRONE | Drug Info | [106] | |||
| 19 | TAN-1496 | Drug Info | [107] | |||
| 20 | CRISNATOL MESILATE | Drug Info | [115] | |||
| 21 | TH-1320 | Drug Info | [90] | |||
| Activator | [+] 1 Activator drugs | + | ||||
| 1 | 2,3-Dimethoxybenzo[i]phenanthridines | Drug Info | [110] | |||
| Binder | [+] 3 Binder drugs | + | ||||
| 1 | 5-hydroxy-1H-indole-3-acetic acid | Drug Info | [113] | |||
| 2 | 7-amino-4-hydroxy-2-naphthalenesulfonic acid | Drug Info | [113] | |||
| 3 | Dibenzo-p-dioxin-2-carboxylic acid | Drug Info | [113] | |||
| Inducer | [+] 2 Inducer drugs | + | ||||
| 1 | KT6006 | Drug Info | [118] | |||
| 2 | KT6528 | Drug Info | [118] | |||
| Intercalator | [+] 1 Intercalator drugs | + | ||||
| 1 | Nogalamycin | Drug Info | [119] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Topotecan | Ligand Info | |||||
| Structure Description | HUMAN DNA TOPOISOMERASE I (70 KDA) IN COMPLEX WITH THE POISON TOPOTECAN AND COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX | PDB:1K4T | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | Yes | [122] |
| PDB Sequence |
QKWKWWEEER
210 YPEGIKWKFL220 EHKGPVFAPP230 YEPLPENVKF240 YYDGKVMKLS250 PKAEEVATFF 260 AKMLDHEYTT270 KEIFRKNFFK280 DWRKEMTNEE290 KNIITNLSKC300 DFTQMSQYFK 310 AQTEARKQMS320 KEEKLKIKEE330 NEKLLKEYGF340 CIMDNHKERI350 ANFKIEPPGL 360 FRGRGNHPKM370 GMLKRRIMPE380 DIIINCSKDA390 KVPSPPPGHK400 WKEVRHDNKV 410 TWLVSWTENI420 QGSIKYIMLN430 PSSRIKGEKD440 WQKYETARRL450 KKCVDKIRNQ 460 YREDWKSKEM470 KVRQRAVALY480 FIDKLALRAG490 NEKEEGETAD500 TVGCCSLRVE 510 HINLHPELDG520 QEYVVEFDFL530 GKDSIRYYNK540 VPVEKRVFKN550 LQLFMENKQP 560 EDDLFDRLNT570 GILNKHLQDL580 MEGLTAKVFR590 TYNASITLQQ600 QLKELTAPDE 610 NIPAKILSYN620 RANRAVAILC630 NHQRAPPKTF640 EKSMMNLQTK650 IDAKKEQLAD 660 ARRDLKSAKA670 DAKVMKDAKT680 KKVVESKKKA690 VQRLEEQLMK700 LEVQATDREE 710 NKQIALGTSK720 LNLDPRITVA731 WCKKWGVPIE741 KIYNKTQREK751 FAWAIDMADE 761 DYEF
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Camptothecin | Ligand Info | |||||
| Structure Description | Human DNA Topoisomerase I (70 Kda) In Complex With The Poison Camptothecin and Covalent Complex With A 22 Base Pair DNA Duplex | PDB:1T8I | ||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | Yes | [123] |
| PDB Sequence |
QKWKWWEEER
210 YPEGIKWKFL220 EHKGPVFAPP230 YEPLPENVKF240 YYDGKVMKLS250 PKAEEVATFF 260 AKMLDHEYTT270 KEIFRKNFFK280 DWRKEMTNEE290 KNIITNLSKC300 DFTQMSQYFK 310 AQTEARKQMS320 KEEKLKIKEE330 NEKLLKEYGF340 CIMDNHKERI350 ANFKIEPPGL 360 FRGRGNHPKM370 GMLKRRIMPE380 DIIINCSKDA390 KVPSPPPGHK400 WKEVRHDNKV 410 TWLVSWTENI420 QGSIKYIMLN430 PSSRIKGEKD440 WQKYETARRL450 KKCVDKIRNQ 460 YREDWKSKEM470 KVRQRAVALY480 FIDKLALRAG490 NEKEEGETAD500 TVGCCSLRVE 510 HINLHPELDG520 QEYVVEFDFL530 GKDSIRYYNK540 VPVEKRVFKN550 LQLFMENKQP 560 EDDLFDRLNT570 GILNKHLQDL580 MEGLTAKVFR590 TYNASITLQQ600 QLKELTAPDE 610 NIPAKILSYN620 RANRAVAILC630 NHQRAPPKTF640 EKSMMNLQTK650 IDAKKEQLAD 660 ARRDLKSAKA670 DAKVMKDAKT680 KKVVESKKKA690 VQRLEEQLMK700 LEVQATDREE 710 NKQIALGTSK720 LNLDPRITVA731 WCKKWGVPIE741 KIYNKTQREK751 FAWAIDMADE 761 DYEF
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| Degree | 13 | Degree centrality | 1.40E-03 | Betweenness centrality | 5.03E-04 |
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| Closeness centrality | 2.41E-01 | Radiality | 1.42E+01 | Clustering coefficient | 2.18E-01 |
| Neighborhood connectivity | 5.47E+01 | Topological coefficient | 9.88E-02 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
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| Drug Resistance Mutation (DRM) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | IL2 Signaling Pathway | |||||
| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | DNA replication | |||||
| PID Pathway | [+] 1 PID Pathways | + | ||||
| 1 | Caspase Cascade in Apoptosis | |||||
| WikiPathways | [+] 1 WikiPathways | + | ||||
| 1 | Integrated Pancreatic Cancer Pathway | |||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Clinical pipeline report, company report or official report of GlaxoSmithKline (2009). | |||||
| REF 2 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 020671. | |||||
| REF 3 | Has nature already identified all useful antibacterial targets Curr Opin Microbiol. 2008 Oct;11(5):387-92. | |||||
| REF 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 5 | 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: 6823). | |||||
| REF 6 | New drugs for the treatment of cancer, 1990-2001. Isr Med Assoc J. 2002 Dec;4(12):1124-31. | |||||
| REF 7 | 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: 7101). | |||||
| REF 8 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
| REF 9 | ClinicalTrials.gov (NCT00005869) Nitrocamptothecin Compared With Gemcitabine in Treating Patients With Unresectable Locally Advanced or Metastatic Pancreatic Cancer. U.S. National Institutes of Health. | |||||
| REF 10 | ClinicalTrials.gov (NCT05374512) A Phase 3, Open-label, Randomised Study of Datopotamab Deruxtecan (Dato-DXd) Versus Investigator's Choice of Chemotherapy in Patients Who Are Not Candidates for PD-1/PD-L1 Inhibitor Therapy in First-line Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer (TROPION Breast02). U.S.National Institutes of Health. | |||||
| REF 11 | Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer. 2006 Oct;6(10):789-802. | |||||
| REF 12 | Edotecarin: a novel topoisomerase I inhibitor. Clin Colorectal Cancer. 2005 May;5(1):27-36. | |||||
| REF 13 | ClinicalTrials.gov (NCT01492101) The BEACON Study (Breast Cancer Outcomes With NKTR-102). U.S. National Institutes of Health. | |||||
| REF 14 | ClinicalTrials.gov (NCT00023972) Gemcitabine With or Without Exatecan Mesylate in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer. U.S. National Institutes of Health. | |||||
| REF 15 | ClinicalTrials.gov (NCT00477282) Karenitecin Versus Topotecan in Patients With Advanced Epithelial Ovarian Cancer. U.S. National Institutes of Health. | |||||
| REF 16 | ClinicalTrials.gov (NCT00430144) Belotecan (CKD-602) in Recurrent or Progressive Carcinoma of Uterine Cervix. U.S. National Institutes of Health. | |||||
| REF 17 | Cancer therapy with beta-lapachone. Curr Cancer Drug Targets. 2002 Sep;2(3):227-42. | |||||
| REF 18 | ClinicalTrials.gov (NCT05865990) Multicenter, Single-arm, 3 Cohort, Phase II Trial of HER3-DXd in Patients With Active Brain Metastases From Metastatic Breast Cancer and Non-small Cell Lung Cancer, and in Patients With Leptomeningeal Disease From Advanced Solid Tumors. U.S.National Institutes of Health. | |||||
| REF 19 | ClinicalTrials.gov (NCT00001427) A Phase II Trial of 72-Hour Continuous IV Infusion of 9-Aminocamptothecin With G-CSF Support in Patients With Advanced Ovarian Cancer Previously Treated With Paclitaxel and Cisplatin. U.S. National Institutes of Health. | |||||
| REF 20 | ClinicalTrials.gov (NCT01124539) Study of AR-67 in Adult Patients With Recurrence of Glioblastoma Multiforme (GBM) or Gliosarcoma. U.S. National Institutes of Health. | |||||
| REF 21 | ClinicalTrials.gov (NCT01803269) Topotecan Hydrochloride or Cyclodextrin-Based Polymer-Camptothecin CRLX101 in Treating Patients With Recurrent Small Cell Lung Cancer. U.S. National Institutes of Health. | |||||
| REF 22 | ClinicalTrials.gov (NCT00080015) Diflomotecan (BN80915) Administered Once Every 3 Weeks in Treating Patients With Sensitive Small Cell Lung Cancer (SCLC). U.S. National Institutes of Health. | |||||
| REF 23 | Phase II study of camtobell inj. (belotecan) in combination with cisplatin in patients with previously untreated, extensive stage small cell lung cancer. Lung Cancer. 2013 Jun;80(3):313-8. | |||||
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| REF 41 | ClinicalTrials.gov (NCT01163071) A Phase 1 Trial of ABI-011 in Patients With Advanced Solid Tumors or Lymphomas. U.S. National Institutes of Health. | |||||
| REF 42 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013469) | |||||
| REF 43 | ClinicalTrials.gov (NCT00450502) Safety of Batracylin in Patients With Solid Tumors and Lymphomas. U.S. National Institutes of Health. | |||||
| REF 44 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014200) | |||||
| REF 45 | ClinicalTrials.gov (NCT01435096) BN80927 in Patients With Advanced Malignant Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 46 | ClinicalTrials.gov (NCT00942799) Dose Escalation Study to Assess the Safety and Tolerability of Genz-644282 in Patients With Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 47 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800037203) | |||||
| REF 48 | ClinicalTrials.gov (NCT00003713) Chemotherapy in Treating Patients With Advanced or Metastatic Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 49 | ClinicalTrials.gov (NCT01748019) ST1968 Intravenous (Weekly) in Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 50 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012192) | |||||
| REF 51 | 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: 8261). | |||||
| REF 52 | Clinical pipeline report, company report or official report of Exelixis. | |||||
| REF 53 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024385) | |||||
| REF 54 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004939) | |||||
| REF 55 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002418) | |||||
| REF 56 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004159) | |||||
| REF 57 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014192) | |||||
| REF 58 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005130) | |||||
| REF 59 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011416) | |||||
| REF 60 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011353) | |||||
| REF 61 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001278) | |||||
| REF 62 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002530) | |||||
| REF 63 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004116) | |||||
| REF 64 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004359) | |||||
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