TANDUTINIB

Investigational

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

Structure Search

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)

HIDE SMILES / InChI

Molecular Formula	C31H42N6O4
Molecular Weight	562.703
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
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	Potency
Tyrosine-protein kinase receptor FLT3 42 Target ID: CHEMBL1974 Sources: https://www.drugbank.ca/drugs/DB05465	Antagonist 2849	0.22 µM [IC50]
Platelet-derived growth factor receptor beta 56 Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12124172	Antagonist 2849	0.2 µM [IC50]
Stem cell growth factor receptor 57 Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12124172	Antagonist 2849	0.17 µM [IC50]
Macrophage colony stimulating factor receptor 24 Target ID: CHEMBL1844 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12124172	Antagonist 2849	3.43 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Glioblastoma 66 Sources: https://clinicaltrials.gov/ct2/show/NCT00667394	Primary	Phase II 1147	Unknown Approved Use Unknown
Acute myelogenous leukemia 18 Sources: https://clinicaltrials.gov/ct2/show/NCT00274248	Primary	Withdrawn	Unknown Approved Use Unknown
Kidney cancer 10 Sources: https://clinicaltrials.gov/ct2/show/NCT00408902	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
576 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16902153/	525 mg 2 times / day multiple, oral dose: 525 mg route of administration: Oral experiment type: MULTIPLE 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
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

AUC

Value	Dose	Analyte	Population
689 ng × day/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16902153/	525 mg 2 times / day multiple, oral dose: 525 mg route of administration: Oral experiment type: MULTIPLE 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
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

T_1/2

Value	Dose	Analyte	Population
1.06 day EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16902153/	525 mg 2 times / day multiple, oral dose: 525 mg route of administration: Oral experiment type: MULTIPLE 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
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

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: https://pubmed.ncbi.nlm.nih.gov/16902153	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/16902153	DLT: Muscular weakness, Diarrhea... Dose limiting toxicities: Muscular weakness (grade 3-4, 66.7%) Diarrhea (grade 3, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/16902153
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: https://pubmed.ncbi.nlm.nih.gov/27663390	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27663390	DLT: Fatigue, Weakness... Dose limiting toxicities: Fatigue (grade 3, 33.3%) Weakness (grade 3, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/27663390
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: https://pubmed.ncbi.nlm.nih.gov/16902153	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/16902153	DLT: Muscular weakness, Fatigue... Dose limiting toxicities: Muscular weakness (grade 3, 16.7%) Fatigue (grade 3, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/16902153
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: https://pubmed.ncbi.nlm.nih.gov/27663390	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27663390	DLT: Blood phosphorus abnormal... Dose limiting toxicities: Blood phosphorus abnormal (grade 3, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/27663390

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: https://pubmed.ncbi.nlm.nih.gov/16902153	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/16902153
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: https://pubmed.ncbi.nlm.nih.gov/16902153	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/16902153
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: https://pubmed.ncbi.nlm.nih.gov/27663390	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27663390
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: https://pubmed.ncbi.nlm.nih.gov/27663390	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27663390
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: https://pubmed.ncbi.nlm.nih.gov/16902153	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/16902153
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: https://pubmed.ncbi.nlm.nih.gov/16902153	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/16902153
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: https://pubmed.ncbi.nlm.nih.gov/27663390	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27663390

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY106920	https://www.001chemical.com/chem/search?q=DY106920
1PlusChem LLC	1P0078KQ	https://www.1pchem.com/search?query=1P0078KQ
A2B Chem	AD36906	http://a2bchem.com/prod/AD36906
AOBIOUS INC	AOB5045	http://aobious.com/aobious/search?search_query=AOB5045
ApexBio Technology	B1526	https://www.apexbt.com/catalogsearch/result/?q=B1526
ApexBio Technology	B7853	https://www.apexbt.com/catalogsearch/result/?q=B7853
AstaTech	41110	http://astatechinc.com/CPSResult.php?CRNO=41110
Axon MedChem	1415	https://www.axonmedchem.com/product/1415
BLD Pharm	BD152374	http://www.bldpharm.com/search/Search.html?keyword=BD152374
BOC Sciences	387867-13-2	http://www.bocsci.com/description.asp?cas=387867-13-2
Capot Chemical	25875	https://www.capotchem.com/search.do?q=25875
Cayman Chemical	12098	http://www.caymanchem.com/app/template/Product.vm/catalog/12098
Chem Scene	CS-0098521	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0098521
Chem Scene	CS-0128	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0128
ChemShuttle	109823	https://www.chemshuttle.com/catalogsearch/result/?q=109823
eMolecules	10713991	https://orderbb.emolecules.com/search/#?query=10713991
eNovation Chemicals	D395232	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D395232&searchbtn.x=0&searchbtn.y=0
Excenen	EX-A1637	http://www.excenen.com/searchresultlist.php?id=EX-A1637
Exclusive Chemistry	2262	http://www.exchemistry.com/chem-catalog/product-2262.html
Hairui	HR135978	http://www.hairuichem.com/en/product/search.do?q=HR135978
KeyOrganics	ES-0051	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=ES-0051
Lab Seeker	SC-23292	http://www.labseeker.com/search.php?keywords=SC-23292&category=0
LabSeeker	SC-23292	http://www.labseeker.com/search.php?keywords=SC-23292&category=0
Matrix Scientific	132329	http://www.matrixscientific.com/132329.html
mcule	MCULE-2424855079	https://mcule.com/MCULE-2424855079/
MedChem Express	HY-10202	https://www.medchemexpress.com/search.html?q=HY-10202A&ft=&fa=&fp=
MedChem Express	HY-10202A	https://www.medchemexpress.com/search.html?q=HY-10202A&ft=&fa=&fp=
Molcore	MC106920	http://www.molcore.com/CatMC106920.html
Molnova	M14334	https://www.molnova.com/en/serch-list.html?keywords=M14334
MolPort	MolPort-006-170-097	https://www.molport.com/shop/molecule-link/MolPort-006-170-097
MolPort	MolPort-046-925-804	https://www.molport.com/shop/molecule-link/MolPort-046-925-804
MuseChem	I003421	https://www.musechem.com/product/I003421.html
Ryan Scientific	Desalkylterbuthylazine	https://ryansci.com/products?q=Desalkylterbuthylazine&list_q=&search_type=exact
Selleck Chemicals	S1043	http://www.selleckchem.com/search.html?searchDTO.searchParam=S1043
ShangHai Biochempartner	BCP000047	http://www.biochempartner.com/search_BCP000047
ShangHai Biochempartner	BCP01370	http://www.biochempartner.com/search_BCP01370
TargetMol	T1667	https://www.targetmol.com/search?keyword=T1667
Tetrahedron	TS39421	http://www.thsci.com/search.do?q=TS39421
Toronto Research Chemicals	T006550	https://www.trc-canada.com/product-detail/?CatNum=T006550

PubMed

Title	Date	PubMed
The lack of target specificity of small molecule anticancer kinase inhibitors is correlated with their ability to damage myocytes in vitro.	2010-12-01	20832415
P-glycoprotein and breast cancer resistance protein affect disposition of tandutinib, a tyrosine kinase inhibitor.	2010-12	20670210
FLT3 inhibitors for the treatment of acute myeloid leukemia.	2010-06	20733555
[FLT3 kinase inhibitors for the treatment of acute leukemia].	2010-06	20622483
Gateways to clinical trials.	2010-04-13	20383346
Antiangiogenic therapy and mechanisms of tumor resistance in malignant glioma.	2010	20414333
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).	2009-10-01	19654408
The FLT3 inhibitor tandutinib (formerly MLN518) has sequence-independent synergistic effects with cytarabine and daunorubicin.	2009-08-15	19625780
ABT-869, a promising multi-targeted tyrosine kinase inhibitor: from bench to bedside.	2009-07-30	19642998
Patient-derived acute myeloid leukemia (AML) bone marrow cells display distinct intracellular kinase phosphorylation patterns.	2009-05-15	21188123
N-(4-Isopropoxyphen-yl)acetamide.	2009-04-10	21583839
Gamma-secretase represents a therapeutic target for the treatment of invasive glioma mediated by the p75 neurotrophin receptor.	2008-11-25	19067488
Detection of FLT3 oncogene mutations in acute myeloid leukemia using conformation sensitive gel electrophoresis.	2008-11	19330068
Id1 is a common downstream target of oncogenic tyrosine kinases in leukemic cells.	2008-09-01	18559972
Tandutinib inhibits FMS receptor signalling, and macrophage and osteoclast formation in vitro.	2008-07	18185521
Can FLT3 inhibitors overcome resistance in AML?	2008-03	18342808
Tandutinib, an oral, small-molecule inhibitor of FLT3 for the treatment of AML and other cancer indications.	2008-01	18175263
FLT3 kinase inhibitors in the management of acute myeloid leukemia.	2007-12	18282363
[Novel molecularly target therapies for leukemia].	2007-01-28	17474469
Phase 1 clinical results with tandutinib (MLN518), a novel FLT3 antagonist, in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome: safety, pharmacokinetics, and pharmacodynamics.	2006-12-01	16902153
Improved synthesis of substituted 6,7-dihydroxy-4-quinazolineamines: tandutinib, erlotinib and gefitinib.	2006-04-10	17962760
[The present status of, and problems with the development of FLT3 kinase inhibitors].	2006-04	16715961
RNAi-induced down-regulation of FLT3 expression in AML cell lines increases sensitivity to MLN518.	2005-04-01	15585651
[Possibility of targeting FLT3 kinase for the treatment of leukemia].	2005-03	16447713
[Current and new therapeutic strategies in acute myeloid leukemia].	2005-03	15791811
Sensitivity of oncogenic KIT mutants to the kinase inhibitors MLN518 and PD180970.	2004-12-01	15304388
Variable sensitivity of FLT3 activation loop mutations to the small molecule tyrosine kinase inhibitor MLN518.	2004-11-01	15256420
Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesis.	2004-11-01	15242881
Identification of orally active, potent, and selective 4-piperazinylquinazolines as antagonists of the platelet-derived growth factor receptor tyrosine kinase family.	2002-08-15	12166950
CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML).	2002-06	12124172

Patents

Sample Use Guides

In Vivo Use Guide

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

Tandutinib inhibited IL-3-independent cell growth and FLT3-ITD autophosphorylation with an IC(50) of 10-100 nM.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:16:18 GMT 2025` Edited by `admin` on `Mon Mar 31 18:16:18 GMT 2025`
Record UNII	E1IO3ICJ9A
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CT-53518

Preferred Name

English

TANDUTINIB

Official Name

English

4-[6-Methoxy-7-[3-(piperidin-1-yl)propoxy]quinazolin-4-yl]-N-[4-(1-methylethoxy)phenyl]piperazine-1-carboxamide

Systematic Name

English

Tandutinib [WHO-DD]

Common Name

English

NSC-759851

Code

English

MLN-518

Code

English

CT53518

Code

English

tandutinib [INN]

Common Name

English

TANDUTINIB [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C129825