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Details

Stereochemistry ABSOLUTE
Molecular Formula C35H56N6O5.ClH
Molecular Weight 677.317
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CEMADOTIN HYDROCHLORIDE

SMILES

Cl.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=MRJQTLJSMQOFTP-JGTKTWDESA-N
InChI=1S/C35H56N6O5.ClH/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);1H/t26-,27-,28-,29-,30-;/m0./s1

HIDE SMILES / InChI
Molecular Formula C35H56N6O5
Molecular Weight 640.8563
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED
Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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.

Originator

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Tubulin
69
Target ID: CHEMBL2094134
Inhibitor
8297
 19.4 µM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.75 μM
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/9704730
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/9704730
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/9704730
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/9704730
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/9704730
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/9704730
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/9704730
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/9704730
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/9704730
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:
https://pubmed.ncbi.nlm.nih.gov/11052630
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:
https://pubmed.ncbi.nlm.nih.gov/11052630
Page: p.322
DLT: Neutropenia...
Dose limiting toxicities:
Neutropenia (grade 4, 100%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/11052630
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:
https://pubmed.ncbi.nlm.nih.gov/11052630
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:
https://pubmed.ncbi.nlm.nih.gov/11052630
Page: p.323
DLT: Neutropenia...
Dose limiting toxicities:
Neutropenia (grade 4, 16.7%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/11052630
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:
https://pubmed.ncbi.nlm.nih.gov/9704730
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:
https://pubmed.ncbi.nlm.nih.gov/9704730
Page: p.2774
DLT: Neutropenic fever...
Dose limiting toxicities:
Neutropenic fever (grade 3, 8.3%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/9704730
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:
https://pubmed.ncbi.nlm.nih.gov/9704730
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:
https://pubmed.ncbi.nlm.nih.gov/9704730
Page: p.2773
DLT: Neutropenia...
Dose limiting toxicities:
Neutropenia (66.7%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/9704730
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:
https://pubmed.ncbi.nlm.nih.gov/11052630
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:
https://pubmed.ncbi.nlm.nih.gov/11052630
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:
https://pubmed.ncbi.nlm.nih.gov/11052630
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:
https://pubmed.ncbi.nlm.nih.gov/11052630
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:
https://pubmed.ncbi.nlm.nih.gov/9704730
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:
https://pubmed.ncbi.nlm.nih.gov/9704730
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:
https://pubmed.ncbi.nlm.nih.gov/9704730
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:
https://pubmed.ncbi.nlm.nih.gov/9704730
Page: p.2773
Sourcing

Sourcing

Vendor/AggregatorIDURL
BOC Sciences
159776-69-9
http://www.bocsci.com/description.asp?cas=159776-69-9
MuseChem
R060089
https://www.musechem.com/product/R060089.html
eMolecules
110064454
https://orderbb.emolecules.com/search/#?query=110064454
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

Patents

20010044451
26
JP2007509861A
8
JP2007538099A
18
JP4806680B2
7

Sample Use Guides

In Vivo Use Guide
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).
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:32:28 GMT 2023
Edited
by admin
on Fri Dec 15 15:32:28 GMT 2023
Record UNII
4LJQ1IXS6C
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CEMADOTIN HYDROCHLORIDE
Common Name English
L-PROLINAMIDE, N,N-DIMETHYL-L-VALYL-L-VALYL-N-METHYL-L-VALYL-L-PROLYL-N-(PHENYLMETHYL)-, HYDROCHLORIDE (1:1)
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C67422
Created by admin on Fri Dec 15 15:32:28 GMT 2023 , Edited by admin on Fri Dec 15 15:32:28 GMT 2023
Code System Code Type Description
CAS
172837-41-1
Created by admin on Fri Dec 15 15:32:28 GMT 2023 , Edited by admin on Fri Dec 15 15:32:28 GMT 2023
PRIMARY
FDA UNII
4LJQ1IXS6C
Created by admin on Fri Dec 15 15:32:28 GMT 2023 , Edited by admin on Fri Dec 15 15:32:28 GMT 2023
PRIMARY
NCI_THESAURUS
C1634
Created by admin on Fri Dec 15 15:32:28 GMT 2023 , Edited by admin on Fri Dec 15 15:32:28 GMT 2023
PRIMARY
PUBCHEM
21143092
Created by admin on Fri Dec 15 15:32:28 GMT 2023 , Edited by admin on Fri Dec 15 15:32:28 GMT 2023
PRIMARY
Related Record Type Details
Structure of CEMADOTIN
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of CEMADOTIN
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