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
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-
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/2484330Curator'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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2484330
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.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2311221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6652807 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
81.9 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3517245 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
24.7 nM × min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3517245 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
92.4 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3517245 |
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
| Dose | Population | Adverse 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: |
DLT: Myelosuppression... Disc. AE: Hepatic failure, Sepsis... Dose limiting toxicities: Myelosuppression (grade 5, 20%) AEs leading todiscontinuation/dose reduction: Hepatic failure (grade 5, 20%) Sources: Sepsis (grade 5, 20%) |
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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: |
DLT: Thrombocytopenia, Thrombocytopenia... Disc. AE: Leukopenia, Sepsis... Other AEs: Leukopenia... Dose limiting toxicities: Thrombocytopenia (grade 4, 20%) AEs leading toThrombocytopenia (grade 4, 5%) discontinuation/dose reduction: Leukopenia (grade 4, 1.7%) Other AEs:Sepsis (grade 5, 1.7%) Leukopenia (grade 4, 11.7%) Sources: |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: |
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: |
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: |
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: |
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: |
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: |
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: |
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Induction chemotherapy response and recurrence rates in correlation with N0 or N+ stage in oral squamous cell cancer (OSCC). | 2010-12 |
|
| Phase II TPDCV protocol for pediatric low-grade hypothalamic/chiasmatic gliomas: 15-year update. | 2010-10 |
|
| Neoadjuvant chemotherapy: does it have benefits for the surgeon in the treatment of advanced squamous cell cancer of the oral cavity? | 2010-06 |
|
| Down-regulation of lung resistance related protein by RNA interference targeting survivin induces the reversal of chemoresistances in hepatocellular carcinoma. | 2009-11-05 |
|
| Evaluation of the paclitaxel-ifosfamide-cisplatin (TIP) combination in relapsed and/or metastatic cervical cancer. | 2009-10-06 |
|
| Association between serotonin transporter availability and overall rating scores of quality of life in healthy volunteers. | 2009-06-15 |
|
| 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). | 2008-06 |
|
| A review of topotecan in combination chemotherapy for advanced cervical cancer. | 2008-02 |
|
| [Expression of MDR1 and GST-pi in osteosarcoma and soft tissue sarcoma and their correlation with chemotherapy resistance]. | 2006-06 |
|
| Randomized use of cyclosporin A (CsA) to modulate P-glycoprotein in children with AML in remission: Pediatric Oncology Group Study 9421. | 2006-02-15 |
|
| Treatments for astrocytic tumors in children: current and emerging strategies. | 2006 |
|
| Phase I-II study of irinotecan (CPT-11) plus nedaplatin (254-S) with recombinant human granulocyte colony-stimulating factor support in patients with advanced or recurrent cervical cancer. | 2004-09-13 |
|
| Failure of alkylating agents to improve induction chemotherapy of oropharyngeal squamous cell cancer. | 2004-08-28 |
|
| E-cadherin-dependent intercellular adhesion enhances chemoresistance. | 2003-11 |
|
| [Chemotherapy of recurrent supratentorial malignant gliomas (phase II study)]. | 2002-01-20 |
|
| BCNU-DBD (Dibromodulcitol) chemotherapy of recurrent supratentorial anaplastic astrocytomas and glioblastomas. | 2002 |
|
| Reversal of multidrug resistance by novel nitrophenyl pyrones, SNF4435C and D. | 2001-11 |
|
| Apoptotic and mitotic activity in squamous cell carcinoma cells after combined modality treatment with gamma-irradiation and dibromodulcitol. | 2001 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8996138
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/6652807
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.
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FDA ORPHAN DRUG |
90295
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NCI_THESAURUS |
C475
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FDA ORPHAN DRUG |
33188
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NCI_THESAURUS |
C798
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C662
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3143
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SUB09005MIG
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DTXSID8020414
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D008936
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m7569
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CHEMBL2104612
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104800
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DB12916
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ACTIVE MOIETY