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Details

Stereochemistry ABSOLUTE
Molecular Formula C35H56N6O5
Molecular Weight 640.8563
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CEMADOTIN

SMILES

CC(C)[C@H](NC(=O)[C@H](C(C)C)N(C)C)C(=O)N(C)[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)N2CCC[C@H]2C(=O)NCC3=CC=CC=C3

InChI

InChIKey=XSAKVDNHFRWJKS-IIZANFQQSA-N
InChI=1S/C35H56N6O5/c1-22(2)28(37-32(43)29(23(3)4)38(7)8)34(45)39(9)30(24(5)6)35(46)41-20-14-18-27(41)33(44)40-19-13-17-26(40)31(42)36-21-25-15-11-10-12-16-25/h10-12,15-16,22-24,26-30H,13-14,17-21H2,1-9H3,(H,36,42)(H,37,43)/t26-,27-,28-,29-,30-/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/9860873 | http://adisinsight.springer.com/drugs/800006853

Cemadotin (LU103793) is a cytotoxic water-soluble pentapeptide analogue of dolastatin 15. The dolastatin peptides were originally isolated from the shell-less mollusc Dolabella auricularia. Cemadotin blocks cells at mitosis. It exerts its antitumor activity by suppressing spindle microtubule dynamics through a distinct molecular mechanism by binding at a novel site in tubulin. Cemadotin was in phase II clinical trials as a promising cancer chemotherapeutic agent. However, this agent appears to be inactive in the treatment of advanced non-small-cell lung cancer and other tumors and this research has been discontinued.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: CHEMBL2094134
19.4 µM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.75 μM
2.5 mg/m² single, intravenous
dose: 2.5 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
CEMADOTIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
0.97 μM
2.5 mg/m² 1 times / day steady-state, intravenous
dose: 2.5 mg/m²
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
CEMADOTIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1.2 μM
3 mg/m² 1 times / day steady-state, intravenous
dose: 3 mg/m²
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
CEMADOTIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
10.1 μM × h
2.5 mg/m² single, intravenous
dose: 2.5 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
CEMADOTIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
10.5 μM × h
2.5 mg/m² 1 times / day steady-state, intravenous
dose: 2.5 mg/m²
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
CEMADOTIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
6.3 μM × h
3 mg/m² 1 times / day steady-state, intravenous
dose: 3 mg/m²
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
CEMADOTIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
13 h
2.5 mg/m² single, intravenous
dose: 2.5 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
CEMADOTIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
10 h
2.5 mg/m² 1 times / day steady-state, intravenous
dose: 2.5 mg/m²
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
CEMADOTIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
11 h
3 mg/m² 1 times / day steady-state, intravenous
dose: 3 mg/m²
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
CEMADOTIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
17.5 mg/m2 1 times / day multiple, intravenous (total)
Highest studied dose
Dose: 17.5 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 17.5 mg/m2, 1 times / day
Sources: Page: p.322
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.322
DLT: Neutropenia...
Dose limiting toxicities:
Neutropenia (grade 4, 100%)
Sources: Page: p.322
12.5 mg/m2 1 times / day multiple, intravenous (total)
MTD
Dose: 12.5 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 12.5 mg/m2, 1 times / day
Sources: Page: p.323
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.323
DLT: Neutropenia...
Dose limiting toxicities:
Neutropenia (grade 4, 16.7%)
Sources: Page: p.323
2.5 mg/m2 1 times / day multiple, intravenous
MTD
Dose: 2.5 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 2.5 mg/m2, 1 times / day
Sources: Page: p.2774
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.2774
DLT: Neutropenic fever...
Dose limiting toxicities:
Neutropenic fever (grade 3, 8.3%)
Sources: Page: p.2774
3 mg/m2 1 times / day multiple, intravenous
Studied dose
Dose: 3 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 3 mg/m2, 1 times / day
Sources: Page: p.2773
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.2773
DLT: Neutropenia...
Dose limiting toxicities:
Neutropenia (66.7%)
Sources: Page: p.2773
AEs

AEs

AESignificanceDosePopulation
Neutropenia grade 4, 100%
DLT
17.5 mg/m2 1 times / day multiple, intravenous (total)
Highest studied dose
Dose: 17.5 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 17.5 mg/m2, 1 times / day
Sources: Page: p.322
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.322
Neutropenia grade 4, 16.7%
DLT
12.5 mg/m2 1 times / day multiple, intravenous (total)
MTD
Dose: 12.5 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 12.5 mg/m2, 1 times / day
Sources: Page: p.323
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.323
Neutropenic fever grade 3, 8.3%
DLT
2.5 mg/m2 1 times / day multiple, intravenous
MTD
Dose: 2.5 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 2.5 mg/m2, 1 times / day
Sources: Page: p.2774
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.2774
Neutropenia 66.7%
DLT
3 mg/m2 1 times / day multiple, intravenous
Studied dose
Dose: 3 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 3 mg/m2, 1 times / day
Sources: Page: p.2773
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.2773
PubMed

PubMed

TitleDatePubMed
LU103793 (NSC D-669356): a synthetic peptide that interacts with microtubules and inhibits mitosis.
1995 Jul 15
Phase I and pharmacokinetic study of the water-soluble dolastatin 15 analog LU103793 in patients with advanced solid malignancies.
1998 Aug
Clinical and pharmacologic phase I study of Cemadotin-HCl (LU103793), a novel antimitotic peptide, given as 24-hour infusion in patients with advanced cancer. A study of the Arbeitsgemeinschaft Internistische Onkologie (AIO) Phase I Group and Arbeitsgruppe Pharmakologie in der Onkologie und Haematologie (APOH) Group of the German Cancer Society.
1998 Dec
Suppression of microtubule dynamics by binding of cemadotin to tubulin: possible mechanism for its antitumor action.
1998 Dec 15
Patents

Sample Use Guides

2.5 mg/m2 as a 5-minute infusion for 5 consecutive days every 3 weeks
Route of Administration: Intravenous
In Vitro Use Guide
Turbidity assays with bovine brain microtubules demonstrated that LU103793 inhibits microtubule polymerization in a concentration-dependent manner (IC50 = 7 uM).
Name Type Language
CEMADOTIN
INN   WHO-DD  
INN  
Official Name English
cemadotin [INN]
Common Name English
NSC-D-669356
Code English
Cemadotin [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C67422
Created by admin on Sat Dec 16 17:08:38 GMT 2023 , Edited by admin on Sat Dec 16 17:08:38 GMT 2023
Code System Code Type Description
SMS_ID
100000082045
Created by admin on Sat Dec 16 17:08:38 GMT 2023 , Edited by admin on Sat Dec 16 17:08:38 GMT 2023
PRIMARY
PUBCHEM
9812632
Created by admin on Sat Dec 16 17:08:38 GMT 2023 , Edited by admin on Sat Dec 16 17:08:38 GMT 2023
PRIMARY
NCI_THESAURUS
C75875
Created by admin on Sat Dec 16 17:08:38 GMT 2023 , Edited by admin on Sat Dec 16 17:08:38 GMT 2023
PRIMARY
INN
7399
Created by admin on Sat Dec 16 17:08:38 GMT 2023 , Edited by admin on Sat Dec 16 17:08:38 GMT 2023
PRIMARY
FDA UNII
6SQ8M7ZSFV
Created by admin on Sat Dec 16 17:08:38 GMT 2023 , Edited by admin on Sat Dec 16 17:08:38 GMT 2023
PRIMARY
CAS
159776-69-9
Created by admin on Sat Dec 16 17:08:38 GMT 2023 , Edited by admin on Sat Dec 16 17:08:38 GMT 2023
PRIMARY
ChEMBL
CHEMBL2104387
Created by admin on Sat Dec 16 17:08:38 GMT 2023 , Edited by admin on Sat Dec 16 17:08:38 GMT 2023
PRIMARY
EPA CompTox
DTXSID70166723
Created by admin on Sat Dec 16 17:08:38 GMT 2023 , Edited by admin on Sat Dec 16 17:08:38 GMT 2023
PRIMARY
EVMPD
SUB07438MIG
Created by admin on Sat Dec 16 17:08:38 GMT 2023 , Edited by admin on Sat Dec 16 17:08:38 GMT 2023
PRIMARY
MESH
C094621
Created by admin on Sat Dec 16 17:08:38 GMT 2023 , Edited by admin on Sat Dec 16 17:08:38 GMT 2023
PRIMARY