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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
Structure of TAK-733

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

HIDE SMILES / InChI

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

Description
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

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
3.2 nM [IC50]
Conditions
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Funbound

ValueDoseCo-administeredAnalytePopulation
3%
single, unknown
TAK-733 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse 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%)
Acneiform dermatitis (grade 3, 14.3%)
AEs leading to
discontinuation/dose reduction:
Acneiform dermatitis (grade 2, 14.3%)
Stomatitis (grade 2, 14.3%)
Other AEs:
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

AEs

AESignificanceDosePopulation
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:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Patents

Sample Use Guides

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
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 Mon Mar 31 22:11:37 GMT 2025
Edited
by admin
on Mon Mar 31 22:11:37 GMT 2025
Record UNII
5J61HSP0QJ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TAK-733
Code English
TAK733
Preferred Name English
MEK INHIBITOR TAK-733
Common Name English
TAK 733 [WHO-DD]
Common Name English
3-[(2R)-2,3-Dihydroxypropyl]-6-fluoro-5-[(2-fluoro-4-iodophenyl)amino]-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione
Systematic Name English
REC-4881
Code English
(R)-3-(2,3-DIHYDROXYPROPYL)-6-FLUORO-5-(2-FLUORO-4-IODOPHENYLAMINO)-8-METHYLPYRIDO(2,3-D)PYRIMIDINE-4,7(3H,8H)-DIONE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C69145
Created by admin on Mon Mar 31 22:11:37 GMT 2025 , Edited by admin on Mon Mar 31 22:11:37 GMT 2025
FDA ORPHAN DRUG 817621
Created by admin on Mon Mar 31 22:11:37 GMT 2025 , Edited by admin on Mon Mar 31 22:11:37 GMT 2025
NCI_THESAURUS C129825
Created by admin on Mon Mar 31 22:11:37 GMT 2025 , Edited by admin on Mon Mar 31 22:11:37 GMT 2025
Code System Code Type Description
EPA CompTox
DTXSID20648089
Created by admin on Mon Mar 31 22:11:37 GMT 2025 , Edited by admin on Mon Mar 31 22:11:37 GMT 2025
PRIMARY
ChEMBL
CHEMBL1615025
Created by admin on Mon Mar 31 22:11:37 GMT 2025 , Edited by admin on Mon Mar 31 22:11:37 GMT 2025
PRIMARY
PUBCHEM
24963252
Created by admin on Mon Mar 31 22:11:37 GMT 2025 , Edited by admin on Mon Mar 31 22:11:37 GMT 2025
PRIMARY
FDA UNII
5J61HSP0QJ
Created by admin on Mon Mar 31 22:11:37 GMT 2025 , Edited by admin on Mon Mar 31 22:11:37 GMT 2025
PRIMARY
DRUG BANK
DB12241
Created by admin on Mon Mar 31 22:11:37 GMT 2025 , Edited by admin on Mon Mar 31 22:11:37 GMT 2025
PRIMARY
SMS_ID
300000041469
Created by admin on Mon Mar 31 22:11:37 GMT 2025 , Edited by admin on Mon Mar 31 22:11:37 GMT 2025
PRIMARY
CAS
1035555-63-5
Created by admin on Mon Mar 31 22:11:37 GMT 2025 , Edited by admin on Mon Mar 31 22:11:37 GMT 2025
PRIMARY
NCI_THESAURUS
C84858
Created by admin on Mon Mar 31 22:11:37 GMT 2025 , Edited by admin on Mon Mar 31 22:11:37 GMT 2025
PRIMARY
Related Record Type Details
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ALLOSTERIC INHIBITOR
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ALLOSTERIC INHIBITOR
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