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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: P11387|||Q9UJN0 Gene ID: 7150.0 Gene Symbol: TOP1 Target Organism: Homo sapiens (Human) Sources: http://adisinsight.springer.com/drugs/800022385 |
|||
Target ID: Q16665 Gene ID: 3091.0 Gene Symbol: HIF1A Target Organism: Homo sapiens (Human) |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
94 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12237769 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12237769 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4712 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12237769 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15187995 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12237769 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15187995 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
155 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15187995 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12237769 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15187995 |
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
Dose | Population | Adverse 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%) AEs leading toNeutropenic sepsis (33.3%) discontinuation/dose reduction: Thrombocytopaenia (33.3%) Sources: Page: p.52Diarrhoea (grade 3, 66.7%) Diarrhoea (grade 2, 33.3%) Neutropenic sepsis (33.3%) Myelosuppression (grade 4, 33.3%) Multiorgan failure (grade 5, 33.3%) |
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 Sources: Page: p.610Dysuria (grade 2, 33.3%) |
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%) Sources: Page: p.52Haematuria (grade 2, 12.5%) |
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%) Sources: Haematuria |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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: |
PubMed
Title | Date | PubMed |
---|---|---|
The S-phase cytotoxicity of camptothecin. | 1991 Mar |
|
Phase I and pharmacokinetic (PK) study of MAG-CPT (PNU 166148): a polymeric derivative of camptothecin (CPT). | 2004 Jul 5 |
|
Development of HPMA copolymer-anticancer conjugates: clinical experience and lessons learnt. | 2009 Nov 12 |
|
Do HPMA copolymer conjugates have a future as clinically useful nanomedicines? A critical overview of current status and future opportunities. | 2010 Feb 17 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15187995
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1995300
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.
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English |
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
100000176113
Created by
admin on Sat Dec 16 18:45:42 GMT 2023 , Edited by admin on Sat Dec 16 18:45:42 GMT 2023
|
PRIMARY | |||
|
1883668-61-8
Created by
admin on Sat Dec 16 18:45:42 GMT 2023 , Edited by admin on Sat Dec 16 18:45:42 GMT 2023
|
PRIMARY | |||
|
C62600
Created by
admin on Sat Dec 16 18:45:42 GMT 2023 , Edited by admin on Sat Dec 16 18:45:42 GMT 2023
|
PRIMARY | |||
|
NFH8D7ZGF5
Created by
admin on Sat Dec 16 18:45:42 GMT 2023 , Edited by admin on Sat Dec 16 18:45:42 GMT 2023
|
PRIMARY | |||
|
10453
Created by
admin on Sat Dec 16 18:45:42 GMT 2023 , Edited by admin on Sat Dec 16 18:45:42 GMT 2023
|
PRIMARY | |||
|
DB05899
Created by
admin on Sat Dec 16 18:45:42 GMT 2023 , Edited by admin on Sat Dec 16 18:45:42 GMT 2023
|
PRIMARY | |||
|
1338695-89-8
Created by
admin on Sat Dec 16 18:45:42 GMT 2023 , Edited by admin on Sat Dec 16 18:45:42 GMT 2023
|
NO STRUCTURE GIVEN |
ACTIVE MOIETY
SUBSTANCE RECORD