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Details

Stereochemistry ACHIRAL
Molecular Formula C20H24BrF2N5O3S
Molecular Weight 532.402
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CP-547632

SMILES

NC(=O)C1=C(NC(=O)NCCCCN2CCCC2)SN=C1OCC3=C(F)C=C(Br)C=C3F

InChI

InChIKey=HXHAJRMTJXHJJZ-UHFFFAOYSA-N
InChI=1S/C20H24BrF2N5O3S/c21-12-9-14(22)13(15(23)10-12)11-31-18-16(17(24)29)19(32-27-18)26-20(30)25-5-1-2-6-28-7-3-4-8-28/h9-10H,1-8,11H2,(H2,24,29)(H2,25,26,30)

HIDE SMILES / InChI

Molecular Formula C20H24BrF2N5O3S
Molecular Weight 532.402
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800012052

Pfizer's CP-547632 is a selective inhibitor of VEGFR-2 tyrosine kinase that was discovered during Pfizer's collaboration with OSI Pharmaceuticals. CP-547632, was identified as a potent inhibitor of the VEGFR-2 and basic fibroblast growth factor (FGF) kinases (IC(50) = 11 and 9 nM, respectively). It is selective relative to epidermal growth factor receptor, platelet-derived growth factor beta, and other related TKs. It also inhibits VEGF-stimulated autophosphorylation of VEGFR-2 in a whole cell assay with an IC(50) value of 6 nM. After oral administration of CP-547632 to mice bearing NIH3T3/H-ras tumors, VEGFR-2 phosphorylation in tumors was inhibited in a dose-dependent fashion (EC(50) = 590 ng/ml). CP-547,632 is a well-tolerated, orally-bioavailable inhibitor presently under clinical investigation for the treatment of human malignancies. CP-547632 is in phase I for the treatment of diabetic retinopathy and age-related macular degeneration.

Originator

Curator's Comment: # OSI Pharmaceuticals; Pfizer

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
11.0 nM [IC50]
9.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
312 ng/mL
200 mg 1 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CP-547632 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
394 ng/mL
250 mg 1 times / day steady-state, oral
dose: 250 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CP-547632 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
142 ng/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CP-547632 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
216 ng/mL
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CP-547632 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
5650 ng × h/mL
200 mg 1 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CP-547632 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
7680 ng × h/mL
250 mg 1 times / day steady-state, oral
dose: 250 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CP-547632 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
5180 ng × h/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CP-547632 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
10900 ng × h/mL
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CP-547632 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
31.5 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CP-547632 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
32.1 h
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CP-547632 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
250 mg 1 times / day steady-state, oral
Highest studied dose
Dose: 250 mg, 1 times / day
Route: oral
Route: steady-state
Dose: 250 mg, 1 times / day
Co-administed with::
paclitaxel(AUC = 6)
carboplatin
Sources: Page: p.85
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: Non-small cell lung cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.85
DLT: diarrhea, rash...
Dose limiting toxicities:
diarrhea (grade 3, 20%)
rash (grade 3, 20%)
Sources: Page: p.85
200 mg 1 times / day steady-state, oral
MTD
Dose: 200 mg, 1 times / day
Route: oral
Route: steady-state
Dose: 200 mg, 1 times / day
Co-administed with::
paclitaxel(AUC = 6)
carboplatin
Sources: Page: p.85
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: Non-small cell lung cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 8
Sources: Page: p.85
DLT: rash...
Dose limiting toxicities:
rash (grade 3, 12.5%)
Sources: Page: p.85
AEs

AEs

AESignificanceDosePopulation
diarrhea grade 3, 20%
DLT
250 mg 1 times / day steady-state, oral
Highest studied dose
Dose: 250 mg, 1 times / day
Route: oral
Route: steady-state
Dose: 250 mg, 1 times / day
Co-administed with::
paclitaxel(AUC = 6)
carboplatin
Sources: Page: p.85
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: Non-small cell lung cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.85
rash grade 3, 20%
DLT
250 mg 1 times / day steady-state, oral
Highest studied dose
Dose: 250 mg, 1 times / day
Route: oral
Route: steady-state
Dose: 250 mg, 1 times / day
Co-administed with::
paclitaxel(AUC = 6)
carboplatin
Sources: Page: p.85
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: Non-small cell lung cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.85
rash grade 3, 12.5%
DLT
200 mg 1 times / day steady-state, oral
MTD
Dose: 200 mg, 1 times / day
Route: oral
Route: steady-state
Dose: 200 mg, 1 times / day
Co-administed with::
paclitaxel(AUC = 6)
carboplatin
Sources: Page: p.85
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: Non-small cell lung cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 8
Sources: Page: p.85
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Pharmacological characterization of CP-547,632, a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for cancer therapy.
2003 Nov 1
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: can also be used topically https://clinicaltrials.gov/ct2/show/NCT02022540
The combination of CP-547632 and paclitaxel and carboplatin was well-tolerated at doses up to 200 mg by mouth daily. Dose-limiting toxicity of CP-547632 at 250 mg consisted of diarrhea and rash.
Route of Administration: Oral
CP-547632 inhibits VEGF-stimulated autophosphorylation of VEGFR-2 in a whole cell assay with an IC(50) value of 6 nM.
Substance Class Chemical
Created
by admin
on Fri Dec 15 18:07:48 GMT 2023
Edited
by admin
on Fri Dec 15 18:07:48 GMT 2023
Record UNII
W1B375O5M2
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CP-547632
Common Name English
CP-547,632
Code English
PAN-90806
Code English
CP-632
Code English
OSI-632
Code English
PAN 90806
Code English
4-ISOTHIAZOLECARBOXAMIDE, 3-((4-BROMO-2,6-DIFLUOROPHENYL)METHOXY)-5-((((4-(1-PYRROLIDINYL)BUTYL)AMINO)CARBONYL)AMINO)-
Systematic Name English
PAN90806
Code English
Classification Tree Code System Code
NCI_THESAURUS C1967
Created by admin on Fri Dec 15 18:07:48 GMT 2023 , Edited by admin on Fri Dec 15 18:07:48 GMT 2023
Code System Code Type Description
CAS
252003-65-9
Created by admin on Fri Dec 15 18:07:48 GMT 2023 , Edited by admin on Fri Dec 15 18:07:48 GMT 2023
PRIMARY
NCI_THESAURUS
C93263
Created by admin on Fri Dec 15 18:07:48 GMT 2023 , Edited by admin on Fri Dec 15 18:07:48 GMT 2023
PRIMARY
DRUG BANK
DB12962
Created by admin on Fri Dec 15 18:07:48 GMT 2023 , Edited by admin on Fri Dec 15 18:07:48 GMT 2023
PRIMARY
EPA CompTox
DTXSID00179866
Created by admin on Fri Dec 15 18:07:48 GMT 2023 , Edited by admin on Fri Dec 15 18:07:48 GMT 2023
PRIMARY
ChEMBL
CHEMBL253969
Created by admin on Fri Dec 15 18:07:48 GMT 2023 , Edited by admin on Fri Dec 15 18:07:48 GMT 2023
PRIMARY
PUBCHEM
9811611
Created by admin on Fri Dec 15 18:07:48 GMT 2023 , Edited by admin on Fri Dec 15 18:07:48 GMT 2023
PRIMARY
SMS_ID
300000041529
Created by admin on Fri Dec 15 18:07:48 GMT 2023 , Edited by admin on Fri Dec 15 18:07:48 GMT 2023
PRIMARY
FDA UNII
W1B375O5M2
Created by admin on Fri Dec 15 18:07:48 GMT 2023 , Edited by admin on Fri Dec 15 18:07:48 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY