SU-14813

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H27FN4O4
Molecular Weight	442.4833
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=C(C(=O)NC[C@H](O)CN2CCOCC2)C(C)=C(N1)\C=C3/C(=O)NC4=CC=C(F)C=C34

InChI

InChIKey=CTNPALGJUAXMMC-PMFHANACSA-N

InChI=1S/C23H27FN4O4/c1-13-20(10-18-17-9-15(24)3-4-19(17)27-22(18)30)26-14(2)21(13)23(31)25-11-16(29)12-28-5-7-32-8-6-28/h3-4,9-10,16,26,29H,5-8,11-12H2,1-2H3,(H,25,31)(H,27,30)/b18-10-/t16-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C23H27FN4O4
Molecular Weight	442.4833
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16891463
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800021861

SU-14813 is an oral, multitargeted tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptors (VEGFR), platelet-derived growth factor receptors (PDGFR), KIT, and fms-like tyrosine kinase 3 (FLT-3). SU-14813 was developed as a next-generation TKI agent following sunitinib (SU-11248) designed to demonstrate optimized pharmacokinetic (PK) and tolerability profiles. SU14813 demonstrated broad and potent antitumor activity equivalent to that of sunitinib, which resulted in tumor regression, growth arrest, growth delay, and prolonged survival in established xenograft cancer models in mice. A phase II trial of SU-14813 in patients with breast cancer was completed. However, according to the Pfizer pipeline development has been discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Vascular endothelial growth factor receptor 2 104 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16891463	Antagonist 2778	0.05 µM [IC50]
Vascular endothelial growth factor receptor 1 41 Target ID: CHEMBL1868 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16891463	Antagonist 2778	0.002 nM [IC50]
Platelet-derived growth factor receptor beta 56 Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16891463	Antagonist 2778	0.004 nM [IC50]
Stem cell growth factor receptor 53 Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16891463	Inhibitor 8297	0.015 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Solid tumors 145 Sources: https://clinicaltrials.gov/ct2/show/NCT00982267 http://adisinsight.springer.com/drugs/800021861	Primary		Phase I 428	Unknown Approved Use Unknown
Breast cancer 434 Sources: http://adisinsight.springer.com/drugs/800021861	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
253 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20605934	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	SU-14813 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
255 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20605934	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SU-14813 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
558 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20605934	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SU-14813 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
2701 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20605934	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	SU-14813 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2878 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20605934	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SU-14813 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
8007 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20605934	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SU-14813 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
19.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20605934	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	SU-14813 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
12.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20605934	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SU-14813 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
28.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20605934	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SU-14813 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
250 mg 1 times / day multiple, oral Highest studied dose Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197	DLT: fatigue... Dose limiting toxicities: fatigue (grade 3, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197
100 mg 1 times / day multiple, oral MTD Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197	Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197
200 mg 1 times / day multiple, oral MTD Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197	DLT: fatigue... Dose limiting toxicities: fatigue (grade 3, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197
150 mg 1 times / day multiple, oral Studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197	unhealthy, ADULT n = 33 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 33 Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197	DLT: hypertension, Brain metastases... Dose limiting toxicities: hypertension (grade 3, 3%) Brain metastases (grade 5, 3%) stomatitis (grade 3, 3%) diarrhea (grade 3, 3%) Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197

AEs

AE	Significance	Dose	Population
fatigue	grade 3, 33.3% DLT	250 mg 1 times / day multiple, oral Highest studied dose Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197
fatigue	grade 3, 16.7% DLT	200 mg 1 times / day multiple, oral MTD Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197
diarrhea	grade 3, 3% DLT	150 mg 1 times / day multiple, oral Studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197	unhealthy, ADULT n = 33 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 33 Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197
hypertension	grade 3, 3% DLT	150 mg 1 times / day multiple, oral Studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197	unhealthy, ADULT n = 33 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 33 Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197
stomatitis	grade 3, 3% DLT	150 mg 1 times / day multiple, oral Studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197	unhealthy, ADULT n = 33 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 33 Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197
Brain metastases	grade 5, 3% DLT	150 mg 1 times / day multiple, oral Studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197	unhealthy, ADULT n = 33 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 33 Sources: https://pubmed.ncbi.nlm.nih.gov/20605934 Page: p.197

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00ECVF	https://www.1pchem.com/search?query=1P00ECVF
1PlusChem LLC	1P00G46N	https://www.1pchem.com/search?query=1P00G46N
AChemBlock	O32473	http://www.achemblock.com/catalogsearch/result/?q=O32473
AChemBlock	O32474	http://www.achemblock.com/catalogsearch/result/?q=O32474
AK Scientific	4072AH	https://aksci.com/item_detail.php?cat=4072AH
AlchemyPharm	AP00200	https://www.alchemypharm.com/pharm/search.do?q=AP00200
Ambeed	A124138	http://www.ambeed.com/search/Search.html?keyword=A124138
Angene	AGN-PC-0RTFUZ	http://www.angenechemical.com/productshow/AGN-PC-0RTFUZ.html
Angene	AGN-PC-0UVYU5	http://www.angenechemical.com/productshow/AGN-PC-0UVYU5.html
ApexBio Technology	A3844	https://www.apexbt.com/catalogsearch/result/?q=A3844
ApexBio Technology	A3846	https://www.apexbt.com/catalogsearch/result/?q=A3846
BLD Pharm	BD210732	http://www.bldpharm.com/search/Search.html?keyword=BD210732
BLD Pharm	BD304614	http://www.bldpharm.com/search/Search.html?keyword=BD304614
BLD Pharm	BD304629	http://www.bldpharm.com/search/Search.html?keyword=BD304629
Chem Scene	CS-0008410	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0008410
Chem Scene	CS-0649	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0649
ChemShuttle	101192	https://www.chemshuttle.com/catalogsearch/result/?q=101192
ChemShuttle	101193	https://www.chemshuttle.com/catalogsearch/result/?q=101193
Hairui	HR108965	http://www.hairuichem.com/en/product/search.do?q=HR108965
Matrix Scientific	120710	http://www.matrixscientific.com/120710.html
Matrix Scientific	143823	http://www.matrixscientific.com/143823.html
MedChem Express	HY-10501	https://www.medchemexpress.com/search.html?q=HY-10501A&ft=&fa=&fp=
MedChem Express	HY-10501A	https://www.medchemexpress.com/search.html?q=HY-10501A&ft=&fa=&fp=
MolPort	MolPort-021-805-010	https://www.molport.com/shop/molecule-link/MolPort-021-805-010
MolPort	MolPort-039-137-722	https://www.molport.com/shop/molecule-link/MolPort-039-137-722
Molcore	MC103045	http://www.molcore.com/CatMC103045.html
ShangHai Biochempartner	BCP14819	http://www.biochempartner.com/search_BCP14819
eMolecules	295311383	https://orderbb.emolecules.com/search/#?query=295311383
eMolecules	44811422	https://orderbb.emolecules.com/search/#?query=44811422
eMolecules	45475433	https://orderbb.emolecules.com/search/#?query=45475433
eMolecules	45475459	https://orderbb.emolecules.com/search/#?query=45475459
eMolecules	46016542	https://orderbb.emolecules.com/search/#?query=46016542
mcule	MCULE-1248021483	https://mcule.com/MCULE-1248021483/
mcule	MCULE-7380996855	https://mcule.com/MCULE-7380996855/
mcule	MCULE-9406670321	https://mcule.com/MCULE-9406670321/

PubMed

Title	Date	PubMed

Patents

Sample Use Guides

In Vivo Use Guide

Escalating doses of SU-14813 from 50 to 250mg/day . Capsules administered daily either as continuous dosing or in cycles of 4 weeks on 1 week off

Route of Administration: Oral

In Vitro Use Guide

SU-14813 inhibited VEGFR-2, PDGFR-h, and KIT phosphorylation in porcine aorta endothelial cells overexpressing these targets, with cellular IC50 values of 5.2, 9.9, and 11.2 nmol/L, respectively. SU-14813 inhibited the growth of U-118MG with an IC50 of 50 to 100 nmol/L.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:53:46 GMT 2023` Edited by `admin` on `Fri Dec 15 15:53:46 GMT 2023`
Record UNII	ZZ6VH5MZ17
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

SU-14813

Common Name

English

1H-PYRROLE-3-CARBOXAMIDE, 5-((Z)-(5-FLUORO-1,2-DIHYDRO-2-OXO-3H-INDOL-3-YLIDENE)METHYL)-N-(2-HYDROXY-3-(4-MORPHOLINYL)PROPYL)-2,4-DIMETHYL-

Systematic Name

English

5-((Z)-(5-FLUORO-2-OXO-1,2-DIHYDRO-3H-INDOL-3-YLIDENE)METHYL)-N-(2-HYDROXY-3-MORPHOLIN-4-YLPROPYL)-2,4-DIMETHYL-1H-PYRROLE-3-CARBOXAMIDE

Systematic Name

English

1H-PYRROLE-3-CARBOXAMIDE, 5-((5-FLUORO-1,2-DIHYDRO-2-OXO-3H-INDOL-3-YLIDENE)METHYL)-N-((2S)-2-HYDROXY-3-(4-MORPHOLINYL)PROPYL)-2,4-DIMETHYL-

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1967