CP-724714

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C27H27N5O3
Molecular Weight	469.535
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

SMILES

COCC(=O)NC\C=C\C1=CC2=C(C=C1)N=CN=C2NC3=CC(C)=C(OC4=CC=C(C)N=C4)C=C3

InChI

InChIKey=LLVZBTWPGQVVLW-SNAWJCMRSA-N

InChI=1S/C27H27N5O3/c1-18-13-21(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/h4-11,13-15,17H,12,16H2,1-3H3,(H,28,33)(H,30,31,32)/b5-4+

HIDE SMILES / InChI

Molecular Formula	C27H27N5O3
Molecular Weight	469.535
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

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

Description

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	Inhibitor 8,297		32.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 434	Primary		Phase II 1,132	Unknown

C_max

Value	Dose	Analyte	Population
4900 ng/mL	400 mg 2 times / day multiple, oral	CP-724714 plasma	Homo sapiens
4900 ng/mL	400 mg 2 times / day single, oral	CP-724714 plasma	Homo sapiens
4940 ng/mL	400 mg 2 times / day multiple, oral	CP-724714 plasma	Homo sapiens
4940 ng/mL	400 mg 2 times / day steady-state, oral	CP-724714 plasma	Homo sapiens
2740 ng/mL	250 mg 2 times / day multiple, oral	CP-724714 plasma	Homo sapiens
3660 ng/mL	250 mg 2 times / day steady-state, oral	CP-724714 plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
11900 ng × h/mL	400 mg 2 times / day multiple, oral	CP-724714 plasma	Homo sapiens
11900 ng × h/mL	400 mg 2 times / day single, oral	CP-724714 plasma	Homo sapiens
14900 ng × h/mL	400 mg 2 times / day multiple, oral	CP-724714 plasma	Homo sapiens
14900 ng × h/mL	400 mg 2 times / day steady-state, oral	CP-724714 plasma	Homo sapiens
7360 ng × h/mL	250 mg 2 times / day multiple, oral	CP-724714 plasma	Homo sapiens
9300 ng × h/mL	250 mg 2 times / day steady-state, oral	CP-724714 plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
4.34 h	400 mg 2 times / day multiple, oral	CP-724714 plasma	Homo sapiens
4.34 h	400 mg 2 times / day single, oral	CP-724714 plasma	Homo sapiens
4.8 h	250 mg 2 times / day multiple, oral	CP-724714 plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
400 mg 2 times / day multiple, oral Highest studied dose	unhealthy, ADULT n = 5
400 mg 2 times / day multiple, oral Highest studied dose	unhealthy, ADULT n = 5	DLT: Hyperbilirubinemia, ALT increased...
250 mg 2 times / day multiple, oral RP2D	unhealthy, ADULT n = 15	DLT: thrombocytopenia, Pulmonary embolism...

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AEs

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AE	Significance	Dose	Population
ALT increased	grade 3, 20% DLT	400 mg 2 times / day multiple, oral Highest studied dose	unhealthy, ADULT n = 5
Hyperbilirubinemia	grade 3, 20% DLT	400 mg 2 times / day multiple, oral Highest studied dose	unhealthy, ADULT n = 5
thrombocytopenia	grade 3, 6.7% DLT	250 mg 2 times / day multiple, oral RP2D	unhealthy, ADULT n = 15
Pulmonary embolism	grade 4, 6.7% DLT	250 mg 2 times / day multiple, oral RP2D	unhealthy, ADULT n = 15

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Sourcing

Sourcing

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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

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PubMed

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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

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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
Record UNII	I05QZ0S4V3
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CP-724714

Code

English

ACETAMIDE, 2-METHOXY-N-(3-(4-((3-METHYL-4-((6-METHYL-3-PYRIDINYL)OXY)PHENYL)AMINO)-6-QUINAZOLINYL)-2-PROPEN-1-YL)-

Systematic Name

English

2-METHOXY-N-((2E)-3-(4-((3-METHYL-4-((6-METHYL-3-PYRIDINYL)OXY)PHENYL)AMINO)-6-QUINAZOLINYL)-2-PROPEN-1-YL)ACETAMIDE

Systematic Name

English

CP-724,714

Code

English

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Classification Tree

Code System

Code

Protein Kinase Inhibitor

NCI_THESAURUS

C1967

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Code System

Code

Type

Description

PUBCHEM

9874913

PRIMARY

ChEMBL

CHEMBL483321

PRIMARY

DRUG BANK

DB12302

PRIMARY

CAS

383432-38-0

PRIMARY

EPA CompTox

DTXSID401026009

PRIMARY

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Related Record

Type

Details


					D9MYY7U9N1

CP-724714 SESQUISUCCINATE

SALT/SOLVATE -> PARENT

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Related Record

Type

Details


					I05QZ0S4V3

CP-724714

ACTIVE MOIETY

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SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Doses

AEs

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2