Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C17H15F2IN4O4 |
Molecular Weight | 504.2267 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1C(=O)C(F)=C(NC2=CC=C(I)C=C2F)C3=C1N=CN(C[C@@H](O)CO)C3=O
InChI
InChIKey=RCLQNICOARASSR-SECBINFHSA-N
InChI=1S/C17H15F2IN4O4/c1-23-15-12(16(27)24(7-21-15)5-9(26)6-25)14(13(19)17(23)28)22-11-3-2-8(20)4-10(11)18/h2-4,7,9,22,25-26H,5-6H2,1H3/t9-/m1/s1
Molecular Formula | C17H15F2IN4O4 |
Molecular Weight | 504.2267 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/21310613 | https://www.ncbi.nlm.nih.gov/pubmed/26439693Curator's Comment: Description was created based on several sources, including http://en.pharmacodia.com/web/drug/1_1108.html
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21310613 | https://www.ncbi.nlm.nih.gov/pubmed/26439693
Curator's Comment: Description was created based on several sources, including http://en.pharmacodia.com/web/drug/1_1108.html
TAK-733 had been developed by Millennium Pharmaceuticals (subsidiary of Takeda) for the treatment of adult patients with advanced non-hematological malignancies. In 2015, Takeda discontinued this studies. TAK-733 is an inhibitor of MEK that exhibits anticancer chemotherapeutic activity. In tumor explant models, TAK-733 induces tumor regression. In colorectal cancer cells and melanoma cells, this compound suppresses cell growth. Additionally, TAK-733 decreases tumor growth and weight in animal models of lung cancer and melanoma.
Originator
Sources: http://adisinsight.springer.com/drugs/800029991
Curator's Comment: # Takeda
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3587 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21310613 |
3.2 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
14.8 ng/mL |
3.2 mg single, oral dose: 3.2 mg route of administration: Oral experiment type: SINGLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
11 ng/mL |
4.4 mg single, oral dose: 4.4 mg route of administration: Oral experiment type: SINGLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
26.2 ng/mL |
6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
28.4 ng/mL |
8.4 mg single, oral dose: 8.4 mg route of administration: Oral experiment type: SINGLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
23 ng/mL |
11.8 mg single, oral dose: 11.8 mg route of administration: Oral experiment type: SINGLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
55.7 ng/mL |
16 mg single, oral dose: 16 mg route of administration: Oral experiment type: SINGLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
60 ng/mL |
22 mg single, oral dose: 22 mg route of administration: Oral experiment type: SINGLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
63 ng/mL |
3.2 mg 1 times / day multiple, oral dose: 3.2 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
24.8 ng/mL |
4.4 mg 1 times / day multiple, oral dose: 4.4 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
59.7 ng/mL |
6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
57.4 ng/mL |
8.4 mg 1 times / day multiple, oral dose: 8.4 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
53.2 ng/mL |
11.8 mg 1 times / day multiple, oral dose: 11.8 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
151 ng/mL |
16 mg 1 times / day multiple, oral dose: 16 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
104.6 ng/mL |
22 mg 1 times / day multiple, oral dose: 22 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
128.6 ng × h/mL |
3.2 mg single, oral dose: 3.2 mg route of administration: Oral experiment type: SINGLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
98.1 ng × h/mL |
4.4 mg single, oral dose: 4.4 mg route of administration: Oral experiment type: SINGLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
331.1 ng × h/mL |
6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
360.4 ng × h/mL |
8.4 mg single, oral dose: 8.4 mg route of administration: Oral experiment type: SINGLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
298.9 ng × h/mL |
11.8 mg single, oral dose: 11.8 mg route of administration: Oral experiment type: SINGLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
640.3 ng × h/mL |
16 mg single, oral dose: 16 mg route of administration: Oral experiment type: SINGLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
766.4 ng × h/mL |
22 mg single, oral dose: 22 mg route of administration: Oral experiment type: SINGLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1051.4 ng × h/mL |
3.2 mg 1 times / day multiple, oral dose: 3.2 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
317.9 ng × h/mL |
4.4 mg 1 times / day multiple, oral dose: 4.4 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
925.2 ng × h/mL |
6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
785.6 ng × h/mL |
8.4 mg 1 times / day multiple, oral dose: 8.4 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
2154.4 ng × h/mL |
16 mg 1 times / day multiple, oral dose: 16 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1394.5 ng × h/mL |
22 mg 1 times / day multiple, oral dose: 22 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
43 h |
11.8 mg 1 times / day multiple, oral dose: 11.8 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
39.9 h |
16 mg 1 times / day multiple, oral dose: 16 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
38.3 h |
22 mg 1 times / day multiple, oral dose: 22 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TAK-733 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3% |
single, unknown |
TAK-733 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
22 mg 1 times / day multiple, oral Highest studied dose Dose: 22 mg, 1 times / day Route: oral Route: multiple Dose: 22 mg, 1 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
DLT: fatigue, Acneiform dermatitis... Disc. AE: Acneiform dermatitis, Stomatitis... Other AEs: Acneiform dermatitis... Dose limiting toxicities: fatigue (grade 3, 14.3%) AEs leading toAcneiform dermatitis (grade 3, 14.3%) discontinuation/dose reduction: Acneiform dermatitis (grade 2, 14.3%) Other AEs:Stomatitis (grade 2, 14.3%) Acneiform dermatitis (grade 3, 14.3%) Sources: |
16 mg 1 times / day multiple, oral MTD Dose: 16 mg, 1 times / day Route: oral Route: multiple Dose: 16 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: |
DLT: Acneiform dermatitis... Dose limiting toxicities: Acneiform dermatitis (grade 3, 66.7%) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Acneiform dermatitis | grade 2, 14.3% Disc. AE |
22 mg 1 times / day multiple, oral Highest studied dose Dose: 22 mg, 1 times / day Route: oral Route: multiple Dose: 22 mg, 1 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Stomatitis | grade 2, 14.3% Disc. AE |
22 mg 1 times / day multiple, oral Highest studied dose Dose: 22 mg, 1 times / day Route: oral Route: multiple Dose: 22 mg, 1 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Acneiform dermatitis | grade 3, 14.3% | 22 mg 1 times / day multiple, oral Highest studied dose Dose: 22 mg, 1 times / day Route: oral Route: multiple Dose: 22 mg, 1 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Acneiform dermatitis | grade 3, 14.3% DLT, Disc. AE |
22 mg 1 times / day multiple, oral Highest studied dose Dose: 22 mg, 1 times / day Route: oral Route: multiple Dose: 22 mg, 1 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
fatigue | grade 3, 14.3% DLT, Disc. AE |
22 mg 1 times / day multiple, oral Highest studied dose Dose: 22 mg, 1 times / day Route: oral Route: multiple Dose: 22 mg, 1 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Acneiform dermatitis | grade 3, 66.7% DLT, Disc. AE |
16 mg 1 times / day multiple, oral MTD Dose: 16 mg, 1 times / day Route: oral Route: multiple Dose: 16 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27650277
Patients received oral TAK-733 once daily on days 1-21 in 28-day treatment cycles. Fifty one patients received TAK-733 at one of eleven dose levels: 0.2 mg (n = 1); 0.4 mg (n = 1); 0.8 mg (n = 2);
1.6 mg (n = 2); 3.2 mg (n = 4); 4.4 mg (n = 4); 6 mg
(n = 4); 8.4 mg (n = 9); 11.8 mg (n = 8); 16 mg (n = 9); and
22 mg (n = 7)
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26918363
TAK-733 reduced the proliferation of MM cell lines with IC50 values in the μM range (2–5 uM) after 48 h treatment as a single agent
Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 22:11:37 GMT 2025
by
admin
on
Mon Mar 31 22:11:37 GMT 2025
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Record UNII |
5J61HSP0QJ
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Record Status |
Validated (UNII)
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Record Version |
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Systematic Name | English |
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NCI_THESAURUS |
C69145
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FDA ORPHAN DRUG |
817621
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NCI_THESAURUS |
C129825
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CHEMBL1615025
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24963252
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DB12241
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300000041469
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1035555-63-5
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C84858
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TARGET -> INHIBITOR |
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IC50
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