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

Details

Stereochemistry ACHIRAL
Molecular Formula C6H12Br2O4
Molecular Weight 307.965
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MITOLACTOL

SMILES

O[C@@H](CBr)[C@@H](O)[C@@H](O)[C@H](O)CBr

InChI

InChIKey=VFKZTMPDYBFSTM-GUCUJZIJSA-N
InChI=1S/C6H12Br2O4/c7-1-3(9)5(11)6(12)4(10)2-8/h3-6,9-12H,1-2H2/t3-,4+,5+,6-

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20842409 | https://www.ncbi.nlm.nih.gov/pubmed/6652807 | https://www.ncbi.nlm.nih.gov/pubmed/8996138 | https://www.ncbi.nlm.nih.gov/pubmed/18142452

Mitolactol is a synthetic derivative of hexitol with antineoplastic and radiosensitizing properties. Mitolactol alkylates DNA via actual or derived epoxide groups, resulting in inhibition of DNA and RNA synthesis.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: CHEMBL2311221
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
81.9 μM
1800 mg/m² single, oral
dose: 1800 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
MITOLACTOL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
24.7 nM × min
1800 mg/m² single, oral
dose: 1800 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
MITOLACTOL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
92.4 min
1800 mg/m² single, oral
dose: 1800 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
MITOLACTOL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
1800 mg/m2 1 times / month multiple, oral
MTD
Dose: 1800 mg/m2, 1 times / month
Route: oral
Route: multiple
Dose: 1800 mg/m2, 1 times / month
Sources: Page: p.756
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 5
Sources: Page: p.756
DLT: Myelosuppression...
Disc. AE: Hepatic failure, Sepsis...
Dose limiting toxicities:
Myelosuppression (grade 5, 20%)
AEs leading to
discontinuation/dose reduction:
Hepatic failure (grade 5, 20%)
Sepsis (grade 5, 20%)
Sources: Page: p.756
180 mg/m2 1 times / day multiple, oral
Studied dose
Dose: 180 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 180 mg/m2, 1 times / day
Sources: Page: p.1893
unhealthy, ADULT
n = 60
Health Status: unhealthy
Condition: squamous cell carcinoma of the Cervix Uteri
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Population Size: 60
Sources: Page: p.1893
DLT: Thrombocytopenia, Thrombocytopenia...
Disc. AE: Leukopenia, Sepsis...
Other AEs: Leukopenia...
Dose limiting toxicities:
Thrombocytopenia (grade 4, 5%)
Thrombocytopenia (grade 4, 20%)
AEs leading to
discontinuation/dose reduction:
Leukopenia (grade 4, 1.7%)
Sepsis (grade 5, 1.7%)
Other AEs:
Leukopenia (grade 4, 11.7%)
Sources: Page: p.1893
AEs

AEs

AESignificanceDosePopulation
Myelosuppression grade 5, 20%
DLT, Disc. AE
1800 mg/m2 1 times / month multiple, oral
MTD
Dose: 1800 mg/m2, 1 times / month
Route: oral
Route: multiple
Dose: 1800 mg/m2, 1 times / month
Sources: Page: p.756
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 5
Sources: Page: p.756
Hepatic failure grade 5, 20%
Disc. AE
1800 mg/m2 1 times / month multiple, oral
MTD
Dose: 1800 mg/m2, 1 times / month
Route: oral
Route: multiple
Dose: 1800 mg/m2, 1 times / month
Sources: Page: p.756
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 5
Sources: Page: p.756
Sepsis grade 5, 20%
Disc. AE
1800 mg/m2 1 times / month multiple, oral
MTD
Dose: 1800 mg/m2, 1 times / month
Route: oral
Route: multiple
Dose: 1800 mg/m2, 1 times / month
Sources: Page: p.756
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 5
Sources: Page: p.756
Leukopenia grade 4, 1.7%
Disc. AE
180 mg/m2 1 times / day multiple, oral
Studied dose
Dose: 180 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 180 mg/m2, 1 times / day
Sources: Page: p.1893
unhealthy, ADULT
n = 60
Health Status: unhealthy
Condition: squamous cell carcinoma of the Cervix Uteri
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Population Size: 60
Sources: Page: p.1893
Leukopenia grade 4, 11.7%
180 mg/m2 1 times / day multiple, oral
Studied dose
Dose: 180 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 180 mg/m2, 1 times / day
Sources: Page: p.1893
unhealthy, ADULT
n = 60
Health Status: unhealthy
Condition: squamous cell carcinoma of the Cervix Uteri
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Population Size: 60
Sources: Page: p.1893
Thrombocytopenia grade 4, 20%
DLT, Disc. AE
180 mg/m2 1 times / day multiple, oral
Studied dose
Dose: 180 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 180 mg/m2, 1 times / day
Sources: Page: p.1893
unhealthy, ADULT
n = 60
Health Status: unhealthy
Condition: squamous cell carcinoma of the Cervix Uteri
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Population Size: 60
Sources: Page: p.1893
Thrombocytopenia grade 4, 5%
DLT, Disc. AE
180 mg/m2 1 times / day multiple, oral
Studied dose
Dose: 180 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 180 mg/m2, 1 times / day
Sources: Page: p.1893
unhealthy, ADULT
n = 60
Health Status: unhealthy
Condition: squamous cell carcinoma of the Cervix Uteri
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Population Size: 60
Sources: Page: p.1893
Sepsis grade 5, 1.7%
Disc. AE
180 mg/m2 1 times / day multiple, oral
Studied dose
Dose: 180 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 180 mg/m2, 1 times / day
Sources: Page: p.1893
unhealthy, ADULT
n = 60
Health Status: unhealthy
Condition: squamous cell carcinoma of the Cervix Uteri
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Population Size: 60
Sources: Page: p.1893
PubMed

PubMed

TitleDatePubMed
Apoptotic and mitotic activity in squamous cell carcinoma cells after combined modality treatment with gamma-irradiation and dibromodulcitol.
2001
Randomized use of cyclosporin A (CsA) to modulate P-glycoprotein in children with AML in remission: Pediatric Oncology Group Study 9421.
2006 Feb 15
A review of topotecan in combination chemotherapy for advanced cervical cancer.
2008 Feb
Adjuvant dibromodulcitol and BCNU chemotherapy in anaplastic astrocytoma: results of a randomised European Organisation for Research and Treatment of Cancer phase III study (EORTC study 26882).
2008 Jun
Phase II TPDCV protocol for pediatric low-grade hypothalamic/chiasmatic gliomas: 15-year update.
2010 Oct
Patents

Sample Use Guides

Patients were randomized to receive cisplatin 50 mg/m2 or the same dose of cisplatin plus mitolactol (C + M) 180 mg/m2 orally on days 2 to 6
Route of Administration: Oral
In Vitro Use Guide
Calf thymus DNA (64mg) in 0.25M sodium cacodylate buffer, pH 7.10 (3 ml) and dibromodulcitol (Mitolactol) (308 mg: 1 mmol) in dimethylsulphoxyde (3.5 ml) were mixed and the reaction was allowed to proceed for 2 days at 37°C. The alkylated DNA was then dialysed against 0.01 M Tris-HC1 (pH 7.0) and 0.01 M NaC1 at 4°C for 48 h and hydrolysed at pH 1 for 30 min at 70°C. The pH of hydrolysate was raised to 10.8 prior to chromatography on a column (2.6 cm × 32 cm) of Sephadex G-10. Elution was performed with aq. NH3 pH 10.8 collecting 6.5ml fractions. Four major UV-absorbing peaks were found of which fractions 10-17 contained oligopyrimidine-nucleotides, fraction 19-21 7-alkylated guanines (A2s0/A26o:l.7), fractions 23-29 guanine (A2s0/A26o:l.1) and fractions 33--44 adenine and 3-alkyladenine together (Aes0/A26o:0.36). 7-Alkylguanine derivatives were separated by rechromatography on a column (17 cm x 1.2 cm) of DowexS0 W (H + form) using 1 M HC1 as eluent, 6.5 ml "fractions were collected.
Name Type Language
MITOLACTOL
INN   MART.   MI   WHO-DD  
INN  
Official Name English
NSC-104800
Code English
MITOLACTOL [MI]
Common Name English
DIBROMODULCITOL
Common Name English
DIBROMDULCIT
Common Name English
1,6-DIBROMO-1,6-DIDEOXY-D-GALACTITOL
Common Name English
Mitolactol [WHO-DD]
Common Name English
GALACTITOL, 1,6-DIBROMO-1,6-DIDEOXY-
Systematic Name English
MITOLACTOL [MART.]
Common Name English
mitolactol [INN]
Common Name English
NCI-C04795
Code English
ELOBROMOL
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 90295
Created by admin on Fri Dec 15 18:54:35 GMT 2023 , Edited by admin on Fri Dec 15 18:54:35 GMT 2023
NCI_THESAURUS C475
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FDA ORPHAN DRUG 33188
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NCI_THESAURUS C798
Created by admin on Fri Dec 15 18:54:35 GMT 2023 , Edited by admin on Fri Dec 15 18:54:35 GMT 2023
Code System Code Type Description
NCI_THESAURUS
C662
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INN
3143
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EVMPD
SUB09005MIG
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EPA CompTox
DTXSID8020414
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MESH
D008936
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MERCK INDEX
m7569
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PRIMARY Merck Index
ChEMBL
CHEMBL2104612
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NSC
104800
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CAS
10318-26-0
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DRUG BANK
DB12916
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SMS_ID
100000080878
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PUBCHEM
5284380
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DRUG CENTRAL
857
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FDA UNII
LJ2P1SIK8Y
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