CP-724714 SESQUISUCCINATE

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	2C27H27N5O3.3C4H6O4
Molecular Weight	1293.3341
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	2
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CCC(O)=O.OC(=O)CCC(O)=O.OC(=O)CCC(O)=O.COCC(=O)NC\C=C\C1=CC=C2N=CN=C(NC3=CC=C(OC4=CC=C(C)N=C4)C(C)=C3)C2=C1.COCC(=O)NC\C=C\C5=CC=C6N=CN=C(NC7=CC=C(OC8=CC=C(C)N=C8)C(C)=C7)C6=C5

InChI

InChIKey=QCQCPVIRLYJQCG-NZTFDADUSA-N

InChI=1S/2C27H27N5O3.3C4H6O4/c2*1-18-13-21(8-11-25(18)35-22-9-6-19(2)29-15-22)32-27-23-14-20(7-10-24(23)30-17-31-27)5-4-12-28-26(33)16-34-3;3*5-3(6)1-2-4(7)8/h2*4-11,13-15,17H,12,16H2,1-3H3,(H,28,33)(H,30,31,32);3*1-2H2,(H,5,6)(H,7,8)/b2*5-4+;;;

HIDE SMILES / InChI

Molecular Formula	C27H27N5O3
Molecular Weight	469.535
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Molecular Formula	C4H6O4
Molecular Weight	118.088
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/17285315
Curator's Comment: description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT00055926 | https://clinicaltrials.gov/ct2/show/NCT00102895

CP 724714 is an orally bioavailable, quinazoline-based, selective small molecule inhibitor of the HER2/erbB2 receptor tyrosine kinase. The compound could have particular potential in the treatment of women with metastatic breast cancer, of which 25-30% over express HER2/erbB2. CP 724714 was in preclinical development with Pfizer.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Receptor protein-tyrosine kinase erbB-2 35 Target ID: CHEMBL1824 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17285315	Inhibitor 8228		32.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 431 Sources: https://clinicaltrials.gov/ct2/show/NCT00102895	Primary		Phase II 1144	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
4900 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17317835	400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CP-724714 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4900 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17805538	400 mg 2 times / day single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	CP-724714 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4940 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17805538	400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CP-724714 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4940 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17317835	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CP-724714 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2740 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17317835	250 mg 2 times / day multiple, oral dose: 250 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CP-724714 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3660 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17317835	250 mg 2 times / day steady-state, oral dose: 250 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CP-724714 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
11900 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17317835	400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CP-724714 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
11900 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17805538	400 mg 2 times / day single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	CP-724714 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
14900 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17805538	400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CP-724714 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
14900 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17317835	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CP-724714 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7360 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17317835	250 mg 2 times / day multiple, oral dose: 250 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CP-724714 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9300 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17317835	250 mg 2 times / day steady-state, oral dose: 250 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CP-724714 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
4.34 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17317835	400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CP-724714 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.34 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17805538	400 mg 2 times / day single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	CP-724714 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17317835	250 mg 2 times / day multiple, oral dose: 250 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CP-724714 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17805538 Page: p.108	unhealthy, ADULT n = 5 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/17805538 Page: p.108	Sources: https://pubmed.ncbi.nlm.nih.gov/17805538 Page: p.108
400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17317835 Page: p.1241	unhealthy, ADULT n = 5 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/17317835 Page: p.1241	DLT: Hyperbilirubinemia, ALT increased... Dose limiting toxicities: Hyperbilirubinemia (grade 3, 20%) ALT increased (grade 3, 20%) Sources: https://pubmed.ncbi.nlm.nih.gov/17317835 Page: p.1241
250 mg 2 times / day multiple, oral RP2D Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17317835 Page: p.1241	unhealthy, ADULT n = 15 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/17317835 Page: p.1241	DLT: thrombocytopenia, Pulmonary embolism... Dose limiting toxicities: thrombocytopenia (grade 3, 6.7%) Pulmonary embolism (grade 4, 6.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/17317835 Page: p.1241

AEs

AE	Significance	Dose	Population
ALT increased	grade 3, 20% DLT	400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17317835 Page: p.1241	unhealthy, ADULT n = 5 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/17317835 Page: p.1241
Hyperbilirubinemia	grade 3, 20% DLT	400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17317835 Page: p.1241	unhealthy, ADULT n = 5 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/17317835 Page: p.1241
thrombocytopenia	grade 3, 6.7% DLT	250 mg 2 times / day multiple, oral RP2D Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17317835 Page: p.1241	unhealthy, ADULT n = 15 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/17317835 Page: p.1241
Pulmonary embolism	grade 4, 6.7% DLT	250 mg 2 times / day multiple, oral RP2D Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17317835 Page: p.1241	unhealthy, ADULT n = 15 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/17317835 Page: p.1241

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY111453	https://www.001chemical.com/chem/search?q=DY111453
1PlusChem LLC	1P007AI6	https://www.1pchem.com/search?query=1P007AI6
AK Scientific	2337AH	https://aksci.com/item_detail.php?cat=2337AH
AK Scientific	SYN1033	https://aksci.com/item_detail.php?cat=SYN1033
AK Scientific	X7480	https://aksci.com/item_detail.php?cat=X7480
Ambeed	A116887	http://www.ambeed.com/search/Search.html?keyword=A116887
Angene	AGN-PC-0RG9WW	http://www.angenechemical.com/productshow/AGN-PC-0RG9WW.html
ApexBio Technology	A2412	https://www.apexbt.com/catalogsearch/result/?q=A2412
AstaTech	C74959	http://astatechinc.com/CPSResult.php?CRNO=C74959
Axon MedChem	1537	https://www.axonmedchem.com/product/1537
BLD Pharm	BD630684	http://www.bldpharm.com/search/Search.html?keyword=BD630684
BioSynth	J-501857	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/J-501857
Capot Chemical	20545	https://www.capotchem.com/search.do?q=20545
Cayman Chemical	19172	http://www.caymanchem.com/app/template/Product.vm/catalog/19172
Chem Scene	CS-0262	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0262
ChemShuttle	109752	https://www.chemshuttle.com/catalogsearch/result/?q=109752
ChemShuttle	157335	https://www.chemshuttle.com/catalogsearch/result/?q=157335
Debye Scientific	DB-028138	https://www.debyesci.com/index.php?id=product&ext[cno]=DB-028138
Excenen	EX-A2355	http://www.excenen.com/searchresultlist.php?id=EX-A2355
Hairui	HR113771	http://www.hairuichem.com/en/product/search.do?q=HR113771
KeyOrganics	AS-16200	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16200
Matrix Scientific	145202	http://www.matrixscientific.com/145202.html
MedChem Express	HY-14674	https://www.medchemexpress.com/search.html?q=HY-14674&ft=&fa=&fp=
MolPort	MolPort-009-679-456	https://www.molport.com/shop/molecule-link/MolPort-009-679-456
Molcore	MC111453	http://www.molcore.com/CatMC111453.html
Molnova	M17499	https://www.molnova.com/en/serch-list.html?keywords=M17499
MuseChem	I002211	https://www.musechem.com/product/I002211.html
MuseChem	I003412	https://www.musechem.com/product/I003412.html
ShangHai Biochempartner	BCP000144	http://www.biochempartner.com/search_BCP000144
ShangHai Biochempartner	BCP01844	http://www.biochempartner.com/search_BCP01844
TargetMol	T4014	https://www.targetmol.com/search?keyword=T4014
eMolecules	275093523	https://orderbb.emolecules.com/search/#?query=275093523
eMolecules	31507573	https://orderbb.emolecules.com/search/#?query=31507573
eMolecules	44842435	https://orderbb.emolecules.com/search/#?query=44842435
eNovation Chemicals	D518750	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D518750&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-1816360303	https://mcule.com/MCULE-1816360303/
mcule	MCULE-2273855098	https://mcule.com/MCULE-2273855098/

PubMed

Title	Date	PubMed
		252160232
Discovery of novel small-molecule inhibitors of human epidermal growth factor receptor-2: combined ligand and target-based approach.	2008 Jun 26	18500794
Role of hepatic transporters in the disposition and hepatotoxicity of a HER2 tyrosine kinase inhibitor CP-724,714.	2009 Apr	19223659

Patents

Sample Use Guides

In Vivo Use Guide

In phase I-II clinical trials subjects received CP-724,714 as continuous oral daily doses on 21-day cycles for a predefined maximal duration of 17 cycles (51 weeks). There was no washout between cycles. The starting dose level was 250 mg QD. In subsequent dose cohorts, 250 mg BID, 400 mg BID, and 250 mg TID were evaluated. The maximal tolerated dose was identified as 250 mg TID.

Route of Administration: Oral

In Vitro Use Guide

CP-724714 inhibits erbB2 receptor autophosphorylation in NIH 3T3 cells expressing a chimeric receptor consisting of the EGFR extracellular domain and the erbB2 intracellular domain (IC50 15 ng/ml) and in vitro growth of SKBr3 cells (IC50 25 ng/ml).

Substance Class	Chemical Created by `admin` on `Wed Jul 05 23:27:24 UTC 2023` Edited by `admin` on `Wed Jul 05 23:27:24 UTC 2023`
Record UNII	D9MYY7U9N1
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CP-724714 SESQUISUCCINATE

Common Name

English

BUTANEDIOIC ACID, COMPD. WITH 2-METHOXY-N-((2E)-3-(4-((3-METHYL-4-((6-METHYL-3-PYRIDINYL)OXY)PHENYL)AMINO)-6-QUINAZOLINYL)-2-PROPEN-1-YL)ACETAMIDE (3:2)

Systematic Name

English

2-METHOXY-N-((2E)-3-(4-(3-METHYL-4-(6-METHYL-3-PYRIDINYL)OXY)PHENYLAMINO)-(6-QUINAZOLINYL)-2-PROPENYL)-ACETAMIDE, BUTANEDIOIC ACID 2:3

Common Name

English

Code System Code Type Description

PUBCHEM

11981427

Created by admin on Wed Jul 05 23:27:24 UTC 2023 , Edited by admin on Wed Jul 05 23:27:24 UTC 2023

PRIMARY

CAS

543681-31-8

Created by admin on Wed Jul 05 23:27:24 UTC 2023 , Edited by admin on Wed Jul 05 23:27:24 UTC 2023

PRIMARY

FDA UNII

D9MYY7U9N1

Created by admin on Wed Jul 05 23:27:24 UTC 2023 , Edited by admin on Wed Jul 05 23:27:24 UTC 2023

PRIMARY

Related Record Type Details


					AB6MNQ6J6L

SUCCINIC ACID

PARENT -> SALT/SOLVATE


					I05QZ0S4V3

CP-724714

PARENT -> SALT/SOLVATE

Related Record Type Details


					I05QZ0S4V3

CP-724714

ACTIVE MOIETY

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/17285315Curator's Comment: description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT00055926 | https://clinicaltrials.gov/ct2/show/NCT00102895

Originator

Approval Year

Targets

Conditions

Approved Use

Cmax

AUC

T1/2

Doses

AEs

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17285315
Curator's Comment: description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT00055926 | https://clinicaltrials.gov/ct2/show/NCT00102895

C_max

T_1/2