CP-547632

Investigational

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 Search

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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14612527
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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Vascular endothelial growth factor receptor 2 104 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14612527	Antagonist 2778		11.0 nM [IC50]
Basic fibroblast growth factor 2 Target ID: CHEMBL3107 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14612527	Inhibitor 8297		9.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Non-small cell lung cancer 206 Sources: https://clinicaltrials.gov/ct2/show/NCT00074854	Primary	Phase II 1132	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: https://clinicaltrials.gov/ct2/show/NCT00096239	Primary	Phase II 1132	Unknown Approved Use Unknown
Age-related macular degeneration 20 Sources: https://clinicaltrials.gov/ct2/show/NCT02022540	Primary	Phase I 428	Unknown Approved Use Unknown
Diabetic retinopathy 17 Sources: https://clinicaltrials.gov/ct2/show/NCT02475109	Primary	Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
312 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17031646	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17031646	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17031646	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17031646	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

Value	Dose	Analyte	Population
5650 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17031646	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17031646	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17031646	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17031646	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
31.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17031646	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17031646	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/17031646 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: https://pubmed.ncbi.nlm.nih.gov/17031646 Page: p.85	DLT: diarrhea, rash... Dose limiting toxicities: diarrhea (grade 3, 20%) rash (grade 3, 20%) Sources: https://pubmed.ncbi.nlm.nih.gov/17031646 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: https://pubmed.ncbi.nlm.nih.gov/17031646 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: https://pubmed.ncbi.nlm.nih.gov/17031646 Page: p.85	DLT: rash... Dose limiting toxicities: rash (grade 3, 12.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/17031646 Page: p.85

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/17031646 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: https://pubmed.ncbi.nlm.nih.gov/17031646 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: https://pubmed.ncbi.nlm.nih.gov/17031646 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: https://pubmed.ncbi.nlm.nih.gov/17031646 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: https://pubmed.ncbi.nlm.nih.gov/17031646 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: https://pubmed.ncbi.nlm.nih.gov/17031646 Page: p.85

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY100683	https://www.001chemical.com/chem/search?q=DY100683
1PlusChem LLC	1P002RC9	https://www.1pchem.com/search?query=1P002RC9
AK Scientific	X5494	https://aksci.com/item_detail.php?cat=X5494
Angene	AGN-PC-0R0YB8	http://www.angenechemical.com/productshow/AGN-PC-0R0YB8.html
AstaTech	43118	http://astatechinc.com/CPSResult.php?CRNO=43118
Axon MedChem	1662	https://www.axonmedchem.com/product/1662
BOC Sciences	252003-65-9	http://www.bocsci.com/description.asp?cas=252003-65-9
Chem Scene	CS-0003189	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0003189
Chem Scene	CS-0025143	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0025143
Matrix Scientific	97193	http://www.matrixscientific.com/097193.html
MedChem Express	HY-13302	https://www.medchemexpress.com/search.html?q=HY-13302B&ft=&fa=&fp=
MedChem Express	HY-13302B	https://www.medchemexpress.com/search.html?q=HY-13302B&ft=&fa=&fp=
MolPort	MolPort-006-827-159	https://www.molport.com/shop/molecule-link/MolPort-006-827-159
MolPort	MolPort-046-836-696	https://www.molport.com/shop/molecule-link/MolPort-046-836-696
Molcore	MC100683	http://www.molcore.com/CatMC100683.html
Molnova	M13744	https://www.molnova.com/en/serch-list.html?keywords=M13744
MuseChem	I006230	https://www.musechem.com/product/I006230.html
Wonderchem	WD05PUN	http://www.wonder-chem.com/search.html?text=WD05PUN
eMolecules	30155425	https://orderbb.emolecules.com/search/#?query=30155425
mcule	MCULE-2885800870	https://mcule.com/MCULE-2885800870/

PubMed

Title	Date	PubMed
		252160342
Pharmacological characterization of CP-547,632, a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for cancer therapy.	2003 Nov 1	14612527
A phase I/randomized phase II, non-comparative, multicenter, open label trial of CP-547,632 in combination with paclitaxel and carboplatin or paclitaxel and carboplatin alone as first-line treatment for advanced non-small cell lung cancer (NSCLC).	2007 Jun	17031646

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 UTC 2023` Edited by `admin` on `Fri Dec 15 18:07:48 UTC 2023`
Record UNII	W1B375O5M2
Record Status	`Validated (UNII)`
Record Version

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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