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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 of CP-724714 SESQUISUCCINATE

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
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

Curator's Comment: CP 724714 was originated through a collaboration between OSI Pharmaceuticals and Pfizer. # OSI Pharmaceuticals and Pfizer

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
32.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
4900 ng/mL
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
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
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
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
11900 ng × h/mL
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
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
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
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
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
4.34 h
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
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
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

Doses

DosePopulationAdverse 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: 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: 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: 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: Page: p.1241
DLT: Hyperbilirubinemia, ALT increased...
Dose limiting toxicities:
Hyperbilirubinemia (grade 3, 20%)
ALT increased (grade 3, 20%)
Sources: 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: 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: Page: p.1241
DLT: thrombocytopenia, Pulmonary embolism...
Dose limiting toxicities:
thrombocytopenia (grade 3, 6.7%)
Pulmonary embolism (grade 4, 6.7%)
Sources: Page: p.1241
AEs

AEs

AESignificanceDosePopulation
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: 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: 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: 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: 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: 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: 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: 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: Page: p.1241
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Role of hepatic transporters in the disposition and hepatotoxicity of a HER2 tyrosine kinase inhibitor CP-724,714.
2009 Apr
Patents

Patents

Sample Use Guides

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
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 Fri Dec 15 15:59:09 GMT 2023
Edited
by admin
on Fri Dec 15 15:59:09 GMT 2023
Record UNII
D9MYY7U9N1
Record Status Validated (UNII)
Record Version
  • Download
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 Fri Dec 15 15:59:09 GMT 2023 , Edited by admin on Fri Dec 15 15:59:09 GMT 2023
PRIMARY
CAS
543681-31-8
Created by admin on Fri Dec 15 15:59:09 GMT 2023 , Edited by admin on Fri Dec 15 15:59:09 GMT 2023
PRIMARY
FDA UNII
D9MYY7U9N1
Created by admin on Fri Dec 15 15:59:09 GMT 2023 , Edited by admin on Fri Dec 15 15:59:09 GMT 2023
PRIMARY
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