TAK-733

Investigational

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 Search

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

Description
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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dual specificity mitogen-activated protein kinase kinase 1 20 Target ID: CHEMBL3587 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21310613	Inhibitor 8297		3.2 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Advanced metastatic melanoma 1 Sources: https://clinicaltrials.gov/ct2/show/NCT00948467	Primary		Phase I 428	Unknown Approved Use Unknown
Advanced nonhematologic malignancies 1 Sources: https://clinicaltrials.gov/ct2/show/NCT00948467 http://adisinsight.springer.com/drugs/800029991	Primary		Phase I 428	Unknown Approved Use 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: 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

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: 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

Vendor/Aggregator	ID	URL
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

Title	Date	PubMed
MEK and the inhibitors: from bench to bedside.	2013 Apr 12	23587417

Patents

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

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