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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

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 3.2 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase I
428
Unknown

Approved Use

Unknown
Primary
Phase I
428
Unknown

Approved Use

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:
https://pubmed.ncbi.nlm.nih.gov/27650277
Page: p.50
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/27650277
Page: p.50
DLT: fatigue, Acneiform dermatitis...
Disc. AE: Stomatitis, Acneiform dermatitis...
Other AEs: Acneiform dermatitis...
Dose limiting toxicities:
fatigue (grade 3, 14.3%)
Acneiform dermatitis (grade 3, 14.3%)
AEs leading to
discontinuation/dose reduction:
Stomatitis (grade 2, 14.3%)
Acneiform dermatitis (grade 2, 14.3%)
Other AEs:
Acneiform dermatitis (grade 3, 14.3%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/27650277
Page: p.50
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:
https://pubmed.ncbi.nlm.nih.gov/27650277
Page: p.50
unhealthy
n = 7
Health Status: unhealthy
Condition: cancer
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/27650277
Page: p.50
DLT: Acneiform dermatitis...
Dose limiting toxicities:
Acneiform dermatitis (grade 3, 66.7%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/27650277
Page: p.50
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:
https://pubmed.ncbi.nlm.nih.gov/27650277
Page: p.50
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/27650277
Page: p.50
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:
https://pubmed.ncbi.nlm.nih.gov/27650277
Page: p.50
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/27650277
Page: p.50
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:
https://pubmed.ncbi.nlm.nih.gov/27650277
Page: p.50
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/27650277
Page: p.50
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:
https://pubmed.ncbi.nlm.nih.gov/27650277
Page: p.50
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/27650277
Page: p.50
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:
https://pubmed.ncbi.nlm.nih.gov/27650277
Page: p.50
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/27650277
Page: p.50
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:
https://pubmed.ncbi.nlm.nih.gov/27650277
Page: p.50
unhealthy
n = 7
Health Status: unhealthy
Condition: cancer
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/27650277
Page: p.50
Sourcing

Sourcing

Vendor/AggregatorIDURL
001 Chemical
DY111397
https://www.001chemical.com/chem/search?q=DY111397
1PlusChem LLC
1P008U0H
https://www.1pchem.com/search?query=1P008U0H
A2B Chem
AE11345
http://a2bchem.com/prod/AE11345
AOBIOUS INC
AOB87182
http://aobious.com/aobious/search?search_query=AOB87182
Ambeed
A118745
http://www.ambeed.com/search/Search.html?keyword=A118745
Angene
AGN-PC-0WCR77
http://www.angenechemical.com/productshow/AGN-PC-0WCR77.html
ApexBio Technology
B1621
https://www.apexbt.com/catalogsearch/result/?q=B1621
BLD Pharm
BD316819
http://www.bldpharm.com/search/Search.html?keyword=BD316819
Cayman Chemical
16998
http://www.caymanchem.com/app/template/Product.vm/catalog/16998
Chem Scene
CS-1283
http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1283
ChemShuttle
104619
https://www.chemshuttle.com/catalogsearch/result/?q=104619
Debye Scientific
DA-48192
https://www.debyesci.com/index.php?id=product&ext[cno]=DA-48192
Lab Seeker
SC-96674
http://www.labseeker.com/search.php?keywords=SC-96674&category=0
LabSeeker
SC-96674
http://www.labseeker.com/search.php?keywords=SC-96674&category=0
Matrix Scientific
145104
http://www.matrixscientific.com/145104.html
MedChem Express
HY-13449
https://www.medchemexpress.com/search.html?q=HY-13449&ft=&fa=&fp=
MolPort
MolPort-023-293-497
https://www.molport.com/shop/molecule-link/MolPort-023-293-497
Molcore
MC111397
http://www.molcore.com/CatMC111397.html
Molnova
M10176
https://www.molnova.com/en/serch-list.html?keywords=M10176
MuseChem
I000213
https://www.musechem.com/product/I000213.html
Selleck Chemicals
S2617
http://www.selleckchem.com/search.html?searchDTO.searchParam=S2617
ShangHai Biochempartner
BCP000711
http://www.biochempartner.com/search_BCP000711
ShangHai Biochempartner
BCP06625
http://www.biochempartner.com/search_BCP06625
TargetMol
T6692
https://www.targetmol.com/search?keyword=T6692
eMolecules
300607492
https://orderbb.emolecules.com/search/#?query=300607492
eMolecules
36516879
https://orderbb.emolecules.com/search/#?query=36516879
eMolecules
36730020
https://orderbb.emolecules.com/search/#?query=36730020
eNovation Chemicals
D567168
https://www.enovationchem.com/Products.asp?SEARCHTEXT=D567168&searchbtn.x=0&searchbtn.y=0
mcule
MCULE-3071783163
https://mcule.com/MCULE-3071783163/
mcule
MCULE-5777896652
https://mcule.com/MCULE-5777896652/
PubMed

PubMed

TitleDatePubMed
MEK and the inhibitors: from bench to bedside.
2013 Apr 12
Patents

Patents

08436200
1
20080255160
1

Sample Use Guides

In Vivo Use Guide
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
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 Sat Dec 16 08:35:37 GMT 2023
Edited
by admin
on Sat Dec 16 08:35:37 GMT 2023
Record UNII
5J61HSP0QJ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TAK-733
Code 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
TAK733
Code English
Classification Tree Code System Code
NCI_THESAURUS C69145
Created by admin on Sat Dec 16 08:35:37 GMT 2023 , Edited by admin on Sat Dec 16 08:35:37 GMT 2023
FDA ORPHAN DRUG 817621
Created by admin on Sat Dec 16 08:35:37 GMT 2023 , Edited by admin on Sat Dec 16 08:35:37 GMT 2023
NCI_THESAURUS C129825
Created by admin on Sat Dec 16 08:35:37 GMT 2023 , Edited by admin on Sat Dec 16 08:35:37 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID20648089
Created by admin on Sat Dec 16 08:35:37 GMT 2023 , Edited by admin on Sat Dec 16 08:35:37 GMT 2023
PRIMARY
ChEMBL
CHEMBL1615025
Created by admin on Sat Dec 16 08:35:37 GMT 2023 , Edited by admin on Sat Dec 16 08:35:37 GMT 2023
PRIMARY
PUBCHEM
24963252
Created by admin on Sat Dec 16 08:35:37 GMT 2023 , Edited by admin on Sat Dec 16 08:35:37 GMT 2023
PRIMARY
FDA UNII
5J61HSP0QJ
Created by admin on Sat Dec 16 08:35:37 GMT 2023 , Edited by admin on Sat Dec 16 08:35:37 GMT 2023
PRIMARY
DRUG BANK
DB12241
Created by admin on Sat Dec 16 08:35:37 GMT 2023 , Edited by admin on Sat Dec 16 08:35:37 GMT 2023
PRIMARY
SMS_ID
300000041469
Created by admin on Sat Dec 16 08:35:37 GMT 2023 , Edited by admin on Sat Dec 16 08:35:37 GMT 2023
PRIMARY
CAS
1035555-63-5
Created by admin on Sat Dec 16 08:35:37 GMT 2023 , Edited by admin on Sat Dec 16 08:35:37 GMT 2023
PRIMARY
NCI_THESAURUS
C84858
Created by admin on Sat Dec 16 08:35:37 GMT 2023 , Edited by admin on Sat Dec 16 08:35:37 GMT 2023
PRIMARY
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Structure of TAK-733
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