Stem definition | Drug id | CAS RN |
---|---|---|
antineoplastics, topoisomerase I inhibitors | 2707 | 123948-87-8 |
None
Property | Value | Reference |
---|---|---|
BDDCS (Biopharmaceutical Drug Disposition Classification System) | 3 | Benet LZ, Broccatelli F, Oprea TI |
S (Water solubility) | 1 mg/mL | Benet LZ, Broccatelli F, Oprea TI |
EoM (Fraction excreted unchanged in urine) | 40 % | Benet LZ, Broccatelli F, Oprea TI |
MRTD (Maximum Recommended Therapeutic Daily Dose) | 6.16 ยตM/kg/day | Contrera JF, Matthews EJ, Kruhlak NL, Benz RD |
BA (Bioavailability) | 32 % | Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H |
Vd (Volume of distribution) | 1.80 L/kg | Lombardo F, Berellini G, Obach RS |
CL (Clearance) | 13 mL/min/kg | Lombardo F, Berellini G, Obach RS |
fu (Fraction unbound in plasma) | 0.65 % | Lombardo F, Berellini G, Obach RS |
t_half (Half-life) | 2.30 hours | Lombardo F, Berellini G, Obach RS |
Date | Agency | Company | Orphan |
---|---|---|---|
May 28, 1996 | FDA | NOVARTIS PHARMS CORP |
MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
---|---|---|---|---|---|---|
Anaemia | 297.69 | 29.33 | 248 | 6104 | 252208 | 50346564 |
Neutrophil count decreased | 206.06 | 29.33 | 105 | 6247 | 45921 | 50552851 |
Febrile neutropenia | 202.32 | 29.33 | 135 | 6217 | 97532 | 50501240 |
Thrombocytopenia | 174.16 | 29.33 | 137 | 6215 | 127536 | 50471236 |
White blood cell count decreased | 171.71 | 29.33 | 131 | 6221 | 116591 | 50482181 |
Neutropenia | 164.58 | 29.33 | 141 | 6211 | 147824 | 50450948 |
Platelet count decreased | 143.55 | 29.33 | 111 | 6241 | 100615 | 50498157 |
Malignant neoplasm progression | 123.87 | 29.33 | 87 | 6265 | 68037 | 50530735 |
Ascites | 118.73 | 29.33 | 67 | 6285 | 35794 | 50562978 |
Red blood cell count decreased | 114.14 | 29.33 | 64 | 6288 | 33771 | 50565001 |
Disease progression | 101.59 | 29.33 | 89 | 6263 | 95777 | 50502995 |
Pancytopenia | 88.97 | 29.33 | 78 | 6274 | 83952 | 50514820 |
Metastases to liver | 84.44 | 29.33 | 44 | 6308 | 20060 | 50578712 |
Ileus | 79.60 | 29.33 | 37 | 6315 | 13192 | 50585580 |
Product use in unapproved indication | 64.54 | 29.33 | 76 | 6276 | 115743 | 50483029 |
Decreased appetite | 63.42 | 29.33 | 100 | 6252 | 200823 | 50397949 |
Febrile bone marrow aplasia | 58.70 | 29.33 | 24 | 6328 | 6287 | 50592485 |
Choroidal infarction | 58.45 | 29.33 | 10 | 6342 | 75 | 50598697 |
Metastases to central nervous system | 57.03 | 29.33 | 28 | 6324 | 11254 | 50587518 |
Metastases to peritoneum | 56.97 | 29.33 | 19 | 6333 | 2814 | 50595958 |
Metastases to lymph nodes | 56.22 | 29.33 | 24 | 6328 | 7000 | 50591772 |
Leukopenia | 50.95 | 29.33 | 52 | 6300 | 67476 | 50531296 |
Pyrexia | 50.58 | 29.33 | 132 | 6220 | 380071 | 50218701 |
Haematotoxicity | 50.35 | 29.33 | 23 | 6329 | 7872 | 50590900 |
Hydronephrosis | 45.58 | 29.33 | 22 | 6330 | 8519 | 50590253 |
Nausea | 43.67 | 29.33 | 189 | 6163 | 705209 | 49893563 |
Alveolar soft part sarcoma | 43.14 | 29.33 | 8 | 6344 | 99 | 50598673 |
Vomiting | 40.36 | 29.33 | 138 | 6214 | 460620 | 50138152 |
Neoplasm progression | 38.95 | 29.33 | 31 | 6321 | 29126 | 50569646 |
General physical health deterioration | 38.26 | 29.33 | 66 | 6286 | 142368 | 50456404 |
Subileus | 38.15 | 29.33 | 14 | 6338 | 2745 | 50596027 |
Dehydration | 36.28 | 29.33 | 67 | 6285 | 152382 | 50446390 |
Ovarian cancer recurrent | 35.15 | 29.33 | 10 | 6342 | 872 | 50597900 |
Myelodysplastic syndrome | 33.82 | 29.33 | 22 | 6330 | 15110 | 50583662 |
Gastrointestinal perforation | 33.18 | 29.33 | 13 | 6339 | 3048 | 50595724 |
Bone marrow failure | 31.93 | 29.33 | 27 | 6325 | 27597 | 50571175 |
Arthralgia | 31.81 | 29.33 | 8 | 6344 | 438694 | 50160078 |
MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
---|---|---|---|---|---|---|
Febrile neutropenia | 146.30 | 31.58 | 116 | 3517 | 112124 | 29458770 |
Anaplastic lymphoma kinase gene mutation | 139.23 | 31.58 | 22 | 3611 | 96 | 29570798 |
Product use in unapproved indication | 137.81 | 31.58 | 101 | 3532 | 86774 | 29484120 |
Thrombocytopenia | 117.98 | 31.58 | 111 | 3522 | 134712 | 29436182 |
Retinal degeneration | 86.48 | 31.58 | 18 | 3615 | 426 | 29570468 |
Small cell lung cancer | 66.39 | 31.58 | 19 | 3614 | 1733 | 29569161 |
Choroidal infarction | 64.48 | 31.58 | 11 | 3622 | 83 | 29570811 |
Neoplasm recurrence | 64.13 | 31.58 | 19 | 3614 | 1958 | 29568936 |
White blood cell count decreased | 63.92 | 31.58 | 64 | 3569 | 83298 | 29487596 |
Febrile bone marrow aplasia | 62.35 | 31.58 | 26 | 3607 | 7325 | 29563569 |
Cardiotoxicity | 58.53 | 31.58 | 22 | 3611 | 4722 | 29566172 |
Pancytopenia | 56.78 | 31.58 | 60 | 3573 | 83108 | 29487786 |
Neoplasm progression | 54.85 | 31.58 | 32 | 3601 | 18580 | 29552314 |
Anaemia | 53.02 | 31.58 | 91 | 3542 | 200860 | 29370034 |
Haematotoxicity | 51.18 | 31.58 | 22 | 3611 | 6677 | 29564217 |
Neutropenia | 49.11 | 31.58 | 70 | 3563 | 131641 | 29439253 |
Malignant neoplasm progression | 46.37 | 31.58 | 51 | 3582 | 73808 | 29497086 |
Retinopathy proliferative | 45.06 | 31.58 | 8 | 3625 | 78 | 29570816 |
Vitreous haemorrhage | 42.78 | 31.58 | 14 | 3619 | 1999 | 29568895 |
Platelet count decreased | 41.01 | 31.58 | 57 | 3576 | 104615 | 29466279 |
Disease progression | 40.44 | 31.58 | 50 | 3583 | 81866 | 29489028 |
Primitive neuroectodermal tumour | 39.83 | 31.58 | 7 | 3626 | 64 | 29570830 |
Rhabdomyosarcoma recurrent | 37.58 | 31.58 | 7 | 3626 | 91 | 29570803 |
Blood lactate dehydrogenase increased | 36.44 | 31.58 | 25 | 3608 | 19184 | 29551710 |
Exophthalmos | 35.40 | 31.58 | 9 | 3624 | 523 | 29570371 |
Neutrophil count decreased | 32.49 | 31.58 | 33 | 3600 | 43534 | 29527360 |
Protein total decreased | 31.82 | 31.58 | 14 | 3619 | 4488 | 29566406 |
MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
---|---|---|---|---|---|---|
Febrile neutropenia | 285.88 | 27.46 | 218 | 8176 | 187439 | 64302899 |
Anaemia | 248.40 | 27.46 | 274 | 8120 | 378406 | 64111932 |
White blood cell count decreased | 213.29 | 27.46 | 171 | 8223 | 157666 | 64332672 |
Neutrophil count decreased | 208.62 | 27.46 | 128 | 8266 | 77068 | 64413270 |
Thrombocytopenia | 200.81 | 27.46 | 192 | 8202 | 223609 | 64266729 |
Product use in unapproved indication | 166.79 | 27.46 | 156 | 8238 | 176462 | 64313876 |
Pancytopenia | 161.74 | 27.46 | 140 | 8254 | 143169 | 64347169 |
Platelet count decreased | 158.07 | 27.46 | 148 | 8246 | 167563 | 64322775 |
Malignant neoplasm progression | 149.52 | 27.46 | 121 | 8273 | 112750 | 64377588 |
Red blood cell count decreased | 140.28 | 27.46 | 84 | 8310 | 48302 | 64442036 |
Anaplastic lymphoma kinase gene mutation | 136.83 | 27.46 | 22 | 8372 | 102 | 64490236 |
Choroidal infarction | 121.47 | 27.46 | 21 | 8373 | 162 | 64490176 |
Neutropenia | 120.82 | 27.46 | 152 | 8242 | 239472 | 64250866 |
Disease progression | 101.83 | 27.46 | 108 | 8286 | 141572 | 64348766 |
Metastases to liver | 94.82 | 27.46 | 51 | 8343 | 23890 | 64466448 |
Neoplasm progression | 93.19 | 27.46 | 61 | 8333 | 40903 | 64449435 |
Ascites | 80.98 | 27.46 | 66 | 8328 | 61935 | 64428403 |
Metastases to lymph nodes | 69.44 | 27.46 | 30 | 8364 | 8687 | 64481651 |
Retinal degeneration | 64.88 | 27.46 | 17 | 8377 | 1050 | 64489288 |
Cardiotoxicity | 64.71 | 27.46 | 30 | 8364 | 10244 | 64480094 |
Pyrexia | 56.58 | 27.46 | 180 | 8214 | 558464 | 63931874 |
Decreased appetite | 53.61 | 27.46 | 115 | 8279 | 281174 | 64209164 |
Metastases to peritoneum | 52.11 | 27.46 | 19 | 8375 | 3528 | 64486810 |
Leukopenia | 52.08 | 27.46 | 65 | 8329 | 101177 | 64389161 |
Metastases to central nervous system | 50.53 | 27.46 | 28 | 8366 | 13884 | 64476454 |
Small cell lung cancer | 45.69 | 27.46 | 16 | 8378 | 2645 | 64487693 |
Febrile bone marrow aplasia | 44.61 | 27.46 | 24 | 8370 | 11231 | 64479107 |
Neoplasm recurrence | 43.91 | 27.46 | 17 | 8377 | 3722 | 64486616 |
Myelosuppression | 43.52 | 27.46 | 31 | 8363 | 23799 | 64466539 |
Retinopathy proliferative | 42.06 | 27.46 | 8 | 8386 | 110 | 64490228 |
Metastases to bone | 40.61 | 27.46 | 28 | 8366 | 20407 | 64469931 |
Arthralgia | 40.51 | 27.46 | 5 | 8389 | 442255 | 64048083 |
Vitreous haemorrhage | 39.72 | 27.46 | 15 | 8379 | 3070 | 64487268 |
Dehydration | 39.40 | 27.46 | 87 | 8307 | 216676 | 64273662 |
Alveolar soft part sarcoma | 37.03 | 27.46 | 7 | 8387 | 93 | 64490245 |
Protein total decreased | 34.50 | 27.46 | 18 | 8376 | 7918 | 64482420 |
Haemoglobin decreased | 33.99 | 27.46 | 77 | 8317 | 194986 | 64295352 |
Haematotoxicity | 33.76 | 27.46 | 21 | 8373 | 12875 | 64477463 |
Acute myeloid leukaemia | 33.25 | 27.46 | 28 | 8366 | 27435 | 64462903 |
Administration related reaction | 29.20 | 27.46 | 6 | 8388 | 125 | 64490213 |
Myelodysplastic syndrome | 29.10 | 27.46 | 26 | 8368 | 27553 | 64462785 |
Ileus | 29.01 | 27.46 | 24 | 8370 | 22942 | 64467396 |
Blood lactate dehydrogenase increased | 28.77 | 27.46 | 28 | 8366 | 33050 | 64457288 |
Leukocoria | 27.74 | 27.46 | 4 | 8390 | 7 | 64490331 |
Choroidal dystrophy | 27.66 | 27.46 | 5 | 8389 | 51 | 64490287 |
None
Source | Code | Description |
---|---|---|
ATC | L01CE01 | ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PLANT ALKALOIDS AND OTHER NATURAL PRODUCTS Topoisomerase 1 (TOP1) inhibitors |
FDA MoA | N0000000176 | Topoisomerase Inhibitors |
FDA EPC | N0000175609 | Topoisomerase Inhibitor |
CHEBI has role | CHEBI:35610 | antineoplastic agents |
CHEBI has role | CHEBI:50276 | topoisomerase I inhibitors |
MeSH PA | D000970 | Antineoplastic Agents |
MeSH PA | D004791 | Enzyme Inhibitors |
MeSH PA | D059004 | Topoisomerase I Inhibitors |
Disease | Relation | SNOMED_ID | DOID |
---|---|---|---|
Small cell carcinoma of lung | indication | 254632001 | DOID:5409 |
Malignant tumor of cervix | indication | 363354003 | DOID:4362 |
Malignant tumor of ovary | indication | 363443007 | DOID:2394 |
Ewing's sarcoma | off-label use | 76909002 | DOID:3369 |
Refractory Osteosarcoma | off-label use | ||
Fibrosis of lung | contraindication | 51615001 | DOID:3770 |
Diarrhea | contraindication | 62315008 | |
Acute infectious disease | contraindication | 63171007 | |
Interstitial pneumonia | contraindication | 64667001 | |
Impaired renal function disorder | contraindication | 197663003 | |
Interstitial lung disease | contraindication | 233703007 | DOID:3082 |
Neutropenic colitis | contraindication | 235755005 | |
Anemia | contraindication | 271737000 | DOID:2355 |
Pregnancy, function | contraindication | 289908002 | |
Thrombocytopenic disorder | contraindication | 302215000 | DOID:1588 |
Neutropenic disorder | contraindication | 303011007 | DOID:1227 |
Bone marrow depression | contraindication | 307762000 | |
Breastfeeding (mother) | contraindication | 413712001 | |
Severe Bone Marrow Depression | contraindication | ||
Radiation Therapy Involving the Lungs | contraindication |
None
None
Dissociation level | Dissociation constant | Type (acidic/basic) |
---|---|---|
pKa1 | 5.44 | acidic |
pKa2 | 10.46 | acidic |
pKa3 | 11.03 | Basic |
pKa4 | 0.57 | Basic |
None
None
Target | Class | Pharos | UniProt | Action | Type | Activity value (-log[M]) | Mechanism action | Bioact source | MoA source |
---|---|---|---|---|---|---|---|---|---|
DNA topoisomerase I, mitochondrial | Enzyme | INHIBITOR | WOMBAT-PK | CHEMBL | |||||
Multidrug resistance protein 1 | Transporter | WOMBAT-PK | |||||||
Canalicular multispecific organic anion transporter 1 | Transporter | WOMBAT-PK | |||||||
Nuclear receptor subfamily 1 group I member 2 | Nuclear hormone receptor | WOMBAT-PK | |||||||
ATP-binding cassette sub-family G member 2 | Transporter | WOMBAT-PK | |||||||
Multidrug resistance-associated protein 4 | Transporter | WOMBAT-PK | |||||||
DNA topoisomerase 1 | Enzyme | Kd | 7.58 | CHEMBL | |||||
Hypoxia-inducible factor 1-alpha | Transcription factor | IC50 | 7.22 | CHEMBL | |||||
Solute carrier family 22 member 2 | Transporter | IC50 | 4.21 | CHEMBL | |||||
Multidrug and toxin extrusion protein 1 | Transporter | IC50 | 5.89 | CHEMBL | |||||
Multidrug and toxin extrusion protein 2 | Transporter | IC50 | 5.07 | CHEMBL | |||||
Cytochrome P450 3A4 | Enzyme | IC50 | 5.82 | DRUG MATRIX | |||||
DNA topoisomerase I | Enzyme | IC50 | 4.70 | CHEMBL | |||||
ORF 73 | Unclassified | AC50 | 5.67 | CHEMBL | |||||
UDP-galactopyranose mutase | Enzyme | AC50 | 5.16 | CHEMBL |
ID | Source |
---|---|
4020977 | VUID |
N0000179716 | NUI |
D02168 | KEGG_DRUG |
119413-54-6 | SECONDARY_CAS_RN |
4020977 | VANDF |
4024032 | VANDF |
C0146224 | UMLSCUI |
CHEBI:63632 | CHEBI |
TTC | PDB_CHEM_ID |
CHEMBL84 | ChEMBL_ID |
CHEMBL1607 | ChEMBL_ID |
D019772 | MESH_DESCRIPTOR_UI |
DB01030 | DRUGBANK_ID |
60700 | PUBCHEM_CID |
7101 | IUPHAR_LIGAND_ID |
6783 | INN_ID |
7M7YKX2N15 | UNII |
203472 | RXNORM |
169084 | MMSL |
178613 | MMSL |
5446 | MMSL |
5602 | MMSL |
d04014 | MMSL |
005981 | NDDF |
005982 | NDDF |
108779005 | SNOMEDCT_US |
108781007 | SNOMEDCT_US |
372536007 | SNOMEDCT_US |
Product | Category | Ingredients | NDC | Form | Quantity | Route | Marketing | Label |
---|---|---|---|---|---|---|---|---|
HYCAMTIN | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0078-0672 | CAPSULE | 0.25 mg | ORAL | NDA | 29 sections |
HYCAMTIN | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0078-0673 | CAPSULE | 1 mg | ORAL | NDA | 29 sections |
HYCAMTIN | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0078-0674 | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION | 4 mg | INTRAVENOUS | NDA | 27 sections |
Topotecan | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0409-0302 | INJECTION, SOLUTION, CONCENTRATE | 1 mg | INTRAVENOUS | NDA | 30 sections |
Topotecan | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0703-4714 | INJECTION, SOLUTION, CONCENTRATE | 1 mg | INTRAVENOUS | NDA | 24 sections |
topotecan hydrochloride | HUMAN PRESCRIPTION DRUG LABEL | 1 | 16729-151 | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION | 4 mg | INTRAVENOUS | ANDA | 24 sections |
Topotecan | HUMAN PRESCRIPTION DRUG LABEL | 1 | 16729-243 | INJECTION | 1 mg | INTRAVENOUS | ANDA | 27 sections |
Topotecan hydrochloride | HUMAN PRESCRIPTION DRUG LABEL | 1 | 45963-615 | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION | 4 mg | INTRAVENOUS | ANDA | 18 sections |
Topotecan Hydrochloride | HUMAN PRESCRIPTION DRUG LABEL | 1 | 55390-370 | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION | 4 mg | INTRAVENOUS | ANDA | 28 sections |
Topotecan Hydrochloride | HUMAN PRESCRIPTION DRUG LABEL | 1 | 63323-762 | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION | 4 mg | INTRAVENOUS | ANDA | 28 sections |
Topotecan Hydrochloride | HUMAN PRESCRIPTION DRUG LABEL | 1 | 63323-762 | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION | 4 mg | INTRAVENOUS | ANDA | 28 sections |
TOPOTECAN | HUMAN PRESCRIPTION DRUG LABEL | 1 | 67457-662 | INJECTION, SOLUTION, CONCENTRATE | 1 mg | INTRAVENOUS | ANDA | 24 sections |
TOPOTECAN HYDROCHLORIDE | HUMAN PRESCRIPTION DRUG LABEL | 1 | 69097-262 | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION | 4 mg | INTRAVENOUS | ANDA | 24 sections |
Topotecan | HUMAN PRESCRIPTION DRUG LABEL | 1 | 71288-127 | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION | 4 mg | INTRAVENOUS | ANDA | 26 sections |