U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C20H16N2O4
Molecular Weight 348.352
Optical Activity ( + )
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CAMPTOTHECIN

SMILES

CC[C@@]1(O)C(=O)OCC2=C1C=C3N(CC4=C3N=C5C=CC=CC5=C4)C2=O

InChI

InChIKey=VSJKWCGYPAHWDS-FQEVSTJZSA-N
InChI=1S/C20H16N2O4/c1-2-20(25)14-8-16-17-12(7-11-5-3-4-6-15(11)21-17)9-22(16)18(23)13(14)10-26-19(20)24/h3-8,25H,2,9-10H2,1H3/t20-/m0/s1

HIDE SMILES / InChI

Molecular Formula C20H16N2O4
Molecular Weight 348.352
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Mureletecan is a water-soluble prodrug, consisting of camptothecin covalently linked to polymeric backbone methacryloylglycynamide, with potential antineoplastic activity. After entering tumor cells, the active moiety camptothecin is slowly released from mureletecan via hydrolysis of the ester linkage. Camptothecin, the active moiety, is an alkaloid isolatable from the Chinese tree Camptotheca acuminata. Camptothecin itself suffers from poor solubility, which is why it is often investigated with a solubilizing conjugate; such as in Mureletecan. Camptothecin binds to and stabilizes the topoisomerase I-DNA covalent complex producing potentially lethal double-stranded DNA breaks when encountered by DNA replication machinery. Camptothecin has also been shown to inhibit HIF1a. Camptothecin has been investigated with a number of solubilizing conjugates as a potential treatment in various forms of cancer.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P11387|||Q9UJN0
Gene ID: 7150.0
Gene Symbol: TOP1
Target Organism: Homo sapiens (Human)
Target ID: Q16665
Gene ID: 3091.0
Gene Symbol: HIF1A
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
94 μg/mL
130 mg/m² 1 times / day multiple, intravenous
dose: 130 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
PNU166148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
56 μg/mL
68 mg/m² 1 times / day multiple, intravenous
dose: 68 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
PNU166148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
4712 μg × h/mL
130 mg/m² 1 times / day multiple, intravenous
dose: 130 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
PNU166148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
10667.5 μg × h/mL
240 mg/m² 1 times / 4 weeks multiple, intravenous
dose: 240 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
PNU166148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
8661 μg × h/mL
68 mg/m² 1 times / day multiple, intravenous
dose: 68 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
PNU166148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
9305.3 μg × h/mL
200 mg/m² 1 times / 4 weeks multiple, intravenous
dose: 200 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
PNU166148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
155 h
240 mg/m² 1 times / 4 weeks multiple, intravenous
dose: 240 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
PNU166148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
7.9 day
68 mg/m² 1 times / day multiple, intravenous
dose: 68 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
PNU166148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
237 h
200 mg/m² 1 times / 4 weeks multiple, intravenous
dose: 200 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
PNU166148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
240 mg/m2 1 times / 4 weeks multiple, intravenous
MTD
Dose: 240 mg/m2, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 240 mg/m2, 1 times / 4 weeks
Sources: Page: p.52
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.52
DLT: Myelosuppression, Neutropenic sepsis...
Disc. AE: Thrombocytopaenia, Diarrhoea...
Dose limiting toxicities:
Myelosuppression (grade 3, 33.3%)
Neutropenic sepsis (33.3%)
AEs leading to
discontinuation/dose reduction:
Thrombocytopaenia (33.3%)
Diarrhoea (grade 3, 66.7%)
Diarrhoea (grade 2, 33.3%)
Neutropenic sepsis (33.3%)
Myelosuppression (grade 4, 33.3%)
Multiorgan failure (grade 5, 33.3%)
Sources: Page: p.52
68 mg/m2 1 times / day multiple, intravenous
MTD
Dose: 68 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 68 mg/m2, 1 times / day
Sources: Page: p.610
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.610
DLT: Haematuria, Dysuria...
Dose limiting toxicities:
Haematuria
Dysuria (grade 2, 33.3%)
Sources: Page: p.610
200 mg/m2 1 times / 4 weeks multiple, intravenous
RP2D
Dose: 200 mg/m2, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 200 mg/m2, 1 times / 4 weeks
Sources: Page: p.52
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 8
Sources: Page: p.52
Other AEs: Dysuria, Haematuria...
Other AEs:
Dysuria (grade 2, 12.5%)
Haematuria (grade 2, 12.5%)
Sources: Page: p.52
130 mg/m2 1 times / day multiple, intravenous
Studied dose
Dose: 130 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 130 mg/m2, 1 times / day
Sources:
unhealthy, ADULT
n = 4
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 4
Sources:
DLT: Dysuria, Haematuria...
Dose limiting toxicities:
Dysuria (grade 2, 75%)
Haematuria
Sources:
AEs

AEs

AESignificanceDosePopulation
Neutropenic sepsis 33.3%
DLT, Disc. AE
240 mg/m2 1 times / 4 weeks multiple, intravenous
MTD
Dose: 240 mg/m2, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 240 mg/m2, 1 times / 4 weeks
Sources: Page: p.52
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.52
Neutropenic sepsis 33.3%
Disc. AE
240 mg/m2 1 times / 4 weeks multiple, intravenous
MTD
Dose: 240 mg/m2, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 240 mg/m2, 1 times / 4 weeks
Sources: Page: p.52
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.52
Thrombocytopaenia 33.3%
Disc. AE
240 mg/m2 1 times / 4 weeks multiple, intravenous
MTD
Dose: 240 mg/m2, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 240 mg/m2, 1 times / 4 weeks
Sources: Page: p.52
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.52
Diarrhoea grade 2, 33.3%
Disc. AE
240 mg/m2 1 times / 4 weeks multiple, intravenous
MTD
Dose: 240 mg/m2, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 240 mg/m2, 1 times / 4 weeks
Sources: Page: p.52
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.52
Myelosuppression grade 3, 33.3%
DLT, Disc. AE
240 mg/m2 1 times / 4 weeks multiple, intravenous
MTD
Dose: 240 mg/m2, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 240 mg/m2, 1 times / 4 weeks
Sources: Page: p.52
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.52
Diarrhoea grade 3, 66.7%
Disc. AE
240 mg/m2 1 times / 4 weeks multiple, intravenous
MTD
Dose: 240 mg/m2, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 240 mg/m2, 1 times / 4 weeks
Sources: Page: p.52
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.52
Myelosuppression grade 4, 33.3%
Disc. AE
240 mg/m2 1 times / 4 weeks multiple, intravenous
MTD
Dose: 240 mg/m2, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 240 mg/m2, 1 times / 4 weeks
Sources: Page: p.52
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.52
Multiorgan failure grade 5, 33.3%
Disc. AE
240 mg/m2 1 times / 4 weeks multiple, intravenous
MTD
Dose: 240 mg/m2, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 240 mg/m2, 1 times / 4 weeks
Sources: Page: p.52
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.52
Haematuria DLT
68 mg/m2 1 times / day multiple, intravenous
MTD
Dose: 68 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 68 mg/m2, 1 times / day
Sources: Page: p.610
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.610
Dysuria grade 2, 33.3%
DLT
68 mg/m2 1 times / day multiple, intravenous
MTD
Dose: 68 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 68 mg/m2, 1 times / day
Sources: Page: p.610
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.610
Dysuria grade 2, 12.5%
200 mg/m2 1 times / 4 weeks multiple, intravenous
RP2D
Dose: 200 mg/m2, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 200 mg/m2, 1 times / 4 weeks
Sources: Page: p.52
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 8
Sources: Page: p.52
Haematuria grade 2, 12.5%
200 mg/m2 1 times / 4 weeks multiple, intravenous
RP2D
Dose: 200 mg/m2, 1 times / 4 weeks
Route: intravenous
Route: multiple
Dose: 200 mg/m2, 1 times / 4 weeks
Sources: Page: p.52
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 8
Sources: Page: p.52
Haematuria DLT
130 mg/m2 1 times / day multiple, intravenous
Studied dose
Dose: 130 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 130 mg/m2, 1 times / day
Sources:
unhealthy, ADULT
n = 4
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 4
Sources:
Dysuria grade 2, 75%
DLT, Disc. AE
130 mg/m2 1 times / day multiple, intravenous
Studied dose
Dose: 130 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 130 mg/m2, 1 times / day
Sources:
unhealthy, ADULT
n = 4
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 4
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Phase I and pharmacokinetic (PK) study of MAG-CPT (PNU 166148): a polymeric derivative of camptothecin (CPT).
2004 Jul 5
The natural inhibitor of DNA topoisomerase I, camptothecin, modulates HIF-1α activity by changing miR expression patterns in human cancer cells.
2014 Jan
Patents

Sample Use Guides

MAG-CPT (camptothecin linked to a water-soluble polymeric backbone methacryloylglycynamide) was administered as a 30-minute infusion once every 4 weeks to patients with advanced solid malignancies. The starting dose was 30 mg/m^2. In total, 23 patients received 47 courses at six dose levels, with a maximum dose of 240 mg/m^2. Dose-limiting toxicities were myelosuppression, neutropenic sepsis, and diarrhea. One patient died after cycle 1 MAG-CPT at the maximum dose. The maximum tolerated dose and dose recommended for further clinical study was 200 mg/m^2.
Route of Administration: Intravenous
In Vitro Use Guide
Human HL-60, MOLT-4, and L-1210 cells were maintained in RPMI-1640 medium supplemented with 10% fetal calf serum, 100 U/mL penicillin, 100 micro-g/mL streptomycin, and 2 mM L-glutamine. All experiments were conducted during the exponential growth phase. To synchronize cells, exponentially growing cultures containing 6 x 10^5 cells per 1 mL were treated with 1 micro-g/mL of aphidicolin for 15 hours; resulting in 80% of the cells in the S-phase. Camptothecin was prepared in dimethyl sulfoxide and diluted in RPMI-1640 to the desired concentrations. Cellular DNA and protein content were measured by flow cytometry and cell viability was assayed by the PI exclusion test. The addition of camptothecin to cultures of myelogenous leukemic cells resulted in rapid (2-6 hours) restructuring of the cell cycle distribution, with a disappearance of S and G2 phase cells and increasing the proportion of G1 cells. Cytotoxic effects of camptothecin were observed at 0.02 micro-g/mL and higher.
Substance Class Chemical
Created
by admin
on Wed Jul 05 23:14:06 UTC 2023
Edited
by admin
on Wed Jul 05 23:14:06 UTC 2023
Record UNII
XT3Z54Z28A
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CAMPTOTHECIN
MI   WHO-DD  
Common Name English
Camptothecin [WHO-DD]
Common Name English
(+)-CAMPTOTHECIN
Common Name English
NSC-94600
Code English
CAMPTOTHECINE
Common Name English
1H-PYRANO(3',4':6,7)INDOLIZINO(1,2-B)QUINOLINE-3,14(4H,12H)-DIONE, 4-ETHYL-4-HYDROXY-, (4S)-
Systematic Name English
TOPOTECAN RELATED COMPOUND C [USP-RS]
Common Name English
TOPOTECAN RELATED COMPOUND C
USP-RS  
Common Name English
CAMPTOTHECIN [MI]
Common Name English
(4S)-4-ETHYL-4-HYDROXY-1H-PYRANO(3',4':6,7)INDOLIZINO(1,2-B)QUINOLINE-3,14(4H,12H)-DIONE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C1904
Created by admin on Wed Jul 05 23:14:06 UTC 2023 , Edited by admin on Wed Jul 05 23:14:06 UTC 2023
Code System Code Type Description
PUBCHEM
24360
Created by admin on Wed Jul 05 23:14:06 UTC 2023 , Edited by admin on Wed Jul 05 23:14:06 UTC 2023
PRIMARY
NCI_THESAURUS
C338
Created by admin on Wed Jul 05 23:14:06 UTC 2023 , Edited by admin on Wed Jul 05 23:14:06 UTC 2023
PRIMARY
EVMPD
SUB25812
Created by admin on Wed Jul 05 23:14:06 UTC 2023 , Edited by admin on Wed Jul 05 23:14:06 UTC 2023
PRIMARY
EPA CompTox
DTXSID0030956
Created by admin on Wed Jul 05 23:14:06 UTC 2023 , Edited by admin on Wed Jul 05 23:14:06 UTC 2023
PRIMARY
DRUG BANK
DB04690
Created by admin on Wed Jul 05 23:14:06 UTC 2023 , Edited by admin on Wed Jul 05 23:14:06 UTC 2023
PRIMARY
CHEBI
27656
Created by admin on Wed Jul 05 23:14:06 UTC 2023 , Edited by admin on Wed Jul 05 23:14:06 UTC 2023
PRIMARY
NSC
94600
Created by admin on Wed Jul 05 23:14:06 UTC 2023 , Edited by admin on Wed Jul 05 23:14:06 UTC 2023
PRIMARY
RS_ITEM_NUM
1672280
Created by admin on Wed Jul 05 23:14:06 UTC 2023 , Edited by admin on Wed Jul 05 23:14:06 UTC 2023
PRIMARY
MESH
D002166
Created by admin on Wed Jul 05 23:14:06 UTC 2023 , Edited by admin on Wed Jul 05 23:14:06 UTC 2023
PRIMARY
MERCK INDEX
M3007
Created by admin on Wed Jul 05 23:14:06 UTC 2023 , Edited by admin on Wed Jul 05 23:14:06 UTC 2023
PRIMARY Merck Index
SMS_ID
100000089959
Created by admin on Wed Jul 05 23:14:06 UTC 2023 , Edited by admin on Wed Jul 05 23:14:06 UTC 2023
PRIMARY
CAS
7689-03-4
Created by admin on Wed Jul 05 23:14:06 UTC 2023 , Edited by admin on Wed Jul 05 23:14:06 UTC 2023
PRIMARY
WIKIPEDIA
CAMPTOTHECIN
Created by admin on Wed Jul 05 23:14:06 UTC 2023 , Edited by admin on Wed Jul 05 23:14:06 UTC 2023
PRIMARY
FDA UNII
XT3Z54Z28A
Created by admin on Wed Jul 05 23:14:06 UTC 2023 , Edited by admin on Wed Jul 05 23:14:06 UTC 2023
PRIMARY
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SALT/SOLVATE -> PARENT
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