Details
Stereochemistry | ACHIRAL |
Molecular Formula | C31H42N6O4 |
Molecular Weight | 562.703 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC2=C(N=CN=C2C=C1OCCCN3CCCCC3)N4CCN(CC4)C(=O)NC5=CC=C(OC(C)C)C=C5
InChI
InChIKey=UXXQOJXBIDBUAC-UHFFFAOYSA-N
InChI=1S/C31H42N6O4/c1-23(2)41-25-10-8-24(9-11-25)34-31(38)37-17-15-36(16-18-37)30-26-20-28(39-3)29(21-27(26)32-22-33-30)40-19-7-14-35-12-5-4-6-13-35/h8-11,20-23H,4-7,12-19H2,1-3H3,(H,34,38)
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/18175263Curator's Comment: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB05465
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18175263
Curator's Comment: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB05465
Millennium Pharmaceuticals Inc's tandutinib (MLN-518), a piperazinyl derivative of quinazoline, is an orally active inhibitor of FLT3 kinase and family members PDGFR beta and c-Kit. Tandutinib inhibited FLT3 phosphorylation, downstream signaling and malignant growth in vitro and in animal models. The drug exhibited limited activity as a single agent in phase I and II clinical trials in patients with AML and myelodysplastic syndrome, but displayed promising antileukemic activity (90% complete remissions) in a phase I/II trial in patients with newly diagnosed AML when administered in combination with cytarabine and daunorubicin. Phase II clinical trials for tandutinib in patients with Glioblastoma have being discontinued. The use of tandutinib to treat AML has been granted fast-track status by the U.S. Food and Drug Administration. Phase II trials were underway., but later withwrawn.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1974 Sources: https://www.drugbank.ca/drugs/DB05465 |
0.22 µM [IC50] | ||
Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12124172 |
0.2 µM [IC50] | ||
Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12124172 |
0.17 µM [IC50] | ||
Target ID: CHEMBL1844 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12124172 |
3.43 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
486 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27663390 |
600 mg 2 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
TANDUTINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1285 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27663390 |
700 mg 2 times / day steady-state, oral dose: 700 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
TANDUTINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4659 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27663390 |
600 mg 2 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
TANDUTINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
8193 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27663390 |
700 mg 2 times / day steady-state, oral dose: 700 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
TANDUTINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
10.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27663390 |
600 mg 2 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
TANDUTINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
13.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27663390 |
700 mg 2 times / day steady-state, oral dose: 700 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
TANDUTINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
700 mg 2 times / day multiple, oral Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: |
unhealthy, ADULT n = 3 Health Status: unhealthy Condition: hematologic cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 3 Sources: |
DLT: Muscular weakness, Diarrhea... Dose limiting toxicities: Muscular weakness (grade 3-4, 66.7%) Sources: Diarrhea (grade 3, 33.3%) |
700 mg 2 times / day multiple, oral Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: Page: p.571 |
unhealthy, ADULT n = 3 Health Status: unhealthy Condition: glioblastoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: Page: p.571 |
DLT: Weakness, Fatigue... Dose limiting toxicities: Weakness (grade 3, 33.3%) Sources: Page: p.571Fatigue (grade 3, 33.3%) |
525 mg 2 times / day multiple, oral MTD Dose: 525 mg, 2 times / day Route: oral Route: multiple Dose: 525 mg, 2 times / day Sources: |
unhealthy, ADULT n = 6 Health Status: unhealthy Condition: hematologic cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 6 Sources: |
DLT: Fatigue, Muscular weakness... Dose limiting toxicities: Fatigue (grade 3, 16.7%) Sources: Muscular weakness (grade 3, 16.7%) |
600 mg 2 times / day multiple, oral MTD Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: Page: p.571 |
unhealthy, ADULT n = 6 Health Status: unhealthy Condition: glioblastoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: Page: p.571 |
DLT: Blood phosphorus abnormal... Dose limiting toxicities: Blood phosphorus abnormal (grade 3, 16.7%) Sources: Page: p.571 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Diarrhea | grade 3, 33.3% DLT |
700 mg 2 times / day multiple, oral Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: |
unhealthy, ADULT n = 3 Health Status: unhealthy Condition: hematologic cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 3 Sources: |
Muscular weakness | grade 3-4, 66.7% DLT, Disc. AE |
700 mg 2 times / day multiple, oral Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: |
unhealthy, ADULT n = 3 Health Status: unhealthy Condition: hematologic cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 3 Sources: |
Fatigue | grade 3, 33.3% DLT |
700 mg 2 times / day multiple, oral Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: Page: p.571 |
unhealthy, ADULT n = 3 Health Status: unhealthy Condition: glioblastoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: Page: p.571 |
Weakness | grade 3, 33.3% DLT |
700 mg 2 times / day multiple, oral Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: Page: p.571 |
unhealthy, ADULT n = 3 Health Status: unhealthy Condition: glioblastoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: Page: p.571 |
Fatigue | grade 3, 16.7% DLT, Disc. AE |
525 mg 2 times / day multiple, oral MTD Dose: 525 mg, 2 times / day Route: oral Route: multiple Dose: 525 mg, 2 times / day Sources: |
unhealthy, ADULT n = 6 Health Status: unhealthy Condition: hematologic cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 6 Sources: |
Muscular weakness | grade 3, 16.7% DLT, Disc. AE |
525 mg 2 times / day multiple, oral MTD Dose: 525 mg, 2 times / day Route: oral Route: multiple Dose: 525 mg, 2 times / day Sources: |
unhealthy, ADULT n = 6 Health Status: unhealthy Condition: hematologic cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 6 Sources: |
Blood phosphorus abnormal | grade 3, 16.7% DLT |
600 mg 2 times / day multiple, oral MTD Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: Page: p.571 |
unhealthy, ADULT n = 6 Health Status: unhealthy Condition: glioblastoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: Page: p.571 |
PubMed
Title | Date | PubMed |
---|---|---|
[Possibility of targeting FLT3 kinase for the treatment of leukemia]. | 2005 Mar |
|
[The present status of, and problems with the development of FLT3 kinase inhibitors]. | 2006 Apr |
|
Improved synthesis of substituted 6,7-dihydroxy-4-quinazolineamines: tandutinib, erlotinib and gefitinib. | 2006 Apr 10 |
|
FLT3 kinase inhibitors in the management of acute myeloid leukemia. | 2007 Dec |
|
[Novel molecularly target therapies for leukemia]. | 2007 Jan 28 |
|
Id1 is a common downstream target of oncogenic tyrosine kinases in leukemic cells. | 2008 Sep 1 |
|
Gateways to clinical trials. | 2010 Jan-Feb |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00408902
oral tandutinib 500 mg twice daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12124172
Tandutinib inhibited IL-3-independent cell growth and FLT3-ITD autophosphorylation with an IC(50) of 10-100 nM.
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C129825
Created by
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NCI_THESAURUS |
C1967
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90237
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100000143101
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C464670
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DTXSID8048947
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SUB118670
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DB05465
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3038522
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OO-66
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C48404
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E1IO3ICJ9A
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759851
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8501
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387867-13-2
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CHEMBL124660
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)