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
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)
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/14612527Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800012052
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
Sources: http://adisinsight.springer.com/drugs/800012052
Curator's Comment: # OSI Pharmaceuticals; Pfizer
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14612527 |
11.0 nM [IC50] | ||
Target ID: CHEMBL3107 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14612527 |
9.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | 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 | Co-administered | 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 |
T1/2
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) Sources: Page: p.85carboplatin |
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%) Sources: Page: p.85rash (grade 3, 20%) |
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) Sources: Page: p.85carboplatin |
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
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) Sources: Page: p.85carboplatin |
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) Sources: Page: p.85carboplatin |
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) Sources: Page: p.85carboplatin |
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 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17031646
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14612527
CP-547632 inhibits VEGF-stimulated autophosphorylation of VEGFR-2 in a whole cell assay with an IC(50) value of 6 nM.
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C1967
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252003-65-9
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C93263
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DB12962
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DTXSID00179866
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CHEMBL253969
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9811611
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W1B375O5M2
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)