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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 of SU-14813

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
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

Curator's Comment: # Pfizer

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
253 ng/mL
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
2701 ng × h/mL
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
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
19.1 h
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
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
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

Doses

DosePopulationAdverse 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: 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: Page: p.197
DLT: fatigue...
Dose limiting toxicities:
fatigue (grade 3, 33.3%)
Sources: 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: 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: 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: 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: Page: p.197
DLT: fatigue...
Dose limiting toxicities:
fatigue (grade 3, 16.7%)
Sources: 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: 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: 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: Page: p.197
AEs

AEs

AESignificanceDosePopulation
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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: Page: p.197
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Pharmacologic inhibition of CDK4/6: mechanistic evidence for selective activity or acquired resistance in acute myeloid leukemia.
2007 Sep 15
Patents

Sample Use Guides

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
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 UTC 2023
Edited
by admin
on Fri Dec 15 15:53:46 UTC 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
Created by admin on Fri Dec 15 15:53:46 UTC 2023 , Edited by admin on Fri Dec 15 15:53:46 UTC 2023
Code System Code Type Description
PUBCHEM
10138259
Created by admin on Fri Dec 15 15:53:46 UTC 2023 , Edited by admin on Fri Dec 15 15:53:46 UTC 2023
PRIMARY
SMS_ID
300000042568
Created by admin on Fri Dec 15 15:53:46 UTC 2023 , Edited by admin on Fri Dec 15 15:53:46 UTC 2023
PRIMARY
EPA CompTox
DTXSID701025698
Created by admin on Fri Dec 15 15:53:46 UTC 2023 , Edited by admin on Fri Dec 15 15:53:46 UTC 2023
PRIMARY
ChEMBL
CHEMBL1721885
Created by admin on Fri Dec 15 15:53:46 UTC 2023 , Edited by admin on Fri Dec 15 15:53:46 UTC 2023
PRIMARY
FDA UNII
ZZ6VH5MZ17
Created by admin on Fri Dec 15 15:53:46 UTC 2023 , Edited by admin on Fri Dec 15 15:53:46 UTC 2023
PRIMARY
ChEMBL
CHEMBL3545160
Created by admin on Fri Dec 15 15:53:46 UTC 2023 , Edited by admin on Fri Dec 15 15:53:46 UTC 2023
PRIMARY
CAS
452105-23-6
Created by admin on Fri Dec 15 15:53:46 UTC 2023 , Edited by admin on Fri Dec 15 15:53:46 UTC 2023
PRIMARY
CAS
627908-92-3
Created by admin on Fri Dec 15 15:53:46 UTC 2023 , Edited by admin on Fri Dec 15 15:53:46 UTC 2023
NON-SPECIFIC STEREOCHEMISTRY
NCI_THESAURUS
C61507
Created by admin on Fri Dec 15 15:53:46 UTC 2023 , Edited by admin on Fri Dec 15 15:53:46 UTC 2023
PRIMARY NCIT
Related Record Type Details
TARGET -> INHIBITOR
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