PERZINFOTEL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H13N2O5P
Molecular Weight	260.1837
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OP(O)(=O)CCN1CCCNC2=C1C(=O)C2=O

InChI

InChIKey=BDABGOLMYNHHTR-UHFFFAOYSA-N

InChI=1S/C9H13N2O5P/c12-8-6-7(9(8)13)11(3-1-2-10-6)4-5-17(14,15)16/h10H,1-5H2,(H2,14,15,16)

HIDE SMILES / InChI

Molecular Formula	C9H13N2O5P
Molecular Weight	260.1837
Charge	0
Count

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

Description
Sources: https://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=2&p_RefId=685790&p_IsPs=N

Perzinfotel (EAA-090) is a novel squaric acid amide derivative that has been identified as a potential treatment for ischemic brain damage resulting from stroke. EAA-090 is a competitive inhibitor at the NMDA-selective subtype of the glutamate receptor. The compound demonstrates potent inhibitory activity in both in vitro and in vivo models of NMDA-induced excitotoxicity and provides neuroprotective efficacy in several animal models of stroke. EAA-090 is unique among competitive NMDA antagonists in displaying a clear separation between predicted efficacious dose and doses that induce PCP-like psychotomimetic side effects in both animals and humans. This unique profile makes EAA-090 an exciting candidate for assessing the neuroprotective potential of the competitive NMDA mechanism.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
NMDA selective glutamate receptor complex 1 Target ID: GO:0017146 Sources: http://www.ncbi.nlm.nih.gov/pubmed/9457246	Antagonist 2778		28.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Stroke 144 Sources: http://adisinsight.springer.com/drugs/800009946	Primary		Preclinical	Unknown Approved Use Unknown
Neuropathic pain 26 Sources: http://adisinsight.springer.com/drugs/800009946	Palliative		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1210 ng/mL OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/rydapt-epar-public-assessment-report_en.pdf	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		MIDOSTAURIN unknown	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
15700 ng × h/mL OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/rydapt-epar-public-assessment-report_en.pdf	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		MIDOSTAURIN unknown	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
20 h OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/rydapt-epar-public-assessment-report_en.pdf	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		MIDOSTAURIN unknown	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.2% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207997s000lbl.pdf			MIDOSTAURIN plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
50 mg 2 times / day steady, oral Recommended Dose: 50 mg, 2 times / day Route: oral Route: steady Dose: 50 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207997Orig1Orig2s000lbl.pdf	unhealthy, 47 years (range: 18-60 years) n = 345 Health Status: unhealthy Condition: AML Age Group: 47 years (range: 18-60 years) Sex: M+F Population Size: 345 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207997Orig1Orig2s000lbl.pdf	Disc. AE: Renal insufficiency... AEs leading to discontinuation/dose reduction: Renal insufficiency (grade 3-4, 2 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207997Orig1Orig2s000lbl.pdf
50 mg 2 times / day steady, oral Recommended Dose: 50 mg, 2 times / day Route: oral Route: steady Dose: 50 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000MedR.pdf Page: p.75	unhealthy, 47 years (range: 18-60 years) n = 345 Health Status: unhealthy Condition: AML Age Group: 47 years (range: 18-60 years) Sex: M+F Population Size: 345 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000MedR.pdf Page: p.75	Disc. AE: Transaminases increased, Rash... AEs leading to discontinuation/dose reduction: Transaminases increased (4 patients) Rash (3 patients) Vomiting (3 patients) Arrhythmia (2 patients) Myocardial ischemia (2 patients) Nausea (2 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000MedR.pdf Page: p.75
300 mg 2 times / day multiple, oral Highest studied dose Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000MedR.pdf Page: p. 23	unhealthy, adult n = 29 Health Status: unhealthy Condition: AML Age Group: adult Population Size: 29 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000MedR.pdf Page: p. 23	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000MedR.pdf Page: p. 23

AEs

AE	Significance	Dose	Population
Renal insufficiency	grade 3-4, 2 patients Disc. AE	50 mg 2 times / day steady, oral Recommended Dose: 50 mg, 2 times / day Route: oral Route: steady Dose: 50 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207997Orig1Orig2s000lbl.pdf	unhealthy, 47 years (range: 18-60 years) n = 345 Health Status: unhealthy Condition: AML Age Group: 47 years (range: 18-60 years) Sex: M+F Population Size: 345 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207997Orig1Orig2s000lbl.pdf
Arrhythmia	2 patients Disc. AE	50 mg 2 times / day steady, oral Recommended Dose: 50 mg, 2 times / day Route: oral Route: steady Dose: 50 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000MedR.pdf Page: p.75	unhealthy, 47 years (range: 18-60 years) n = 345 Health Status: unhealthy Condition: AML Age Group: 47 years (range: 18-60 years) Sex: M+F Population Size: 345 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000MedR.pdf Page: p.75
Myocardial ischemia	2 patients Disc. AE	50 mg 2 times / day steady, oral Recommended Dose: 50 mg, 2 times / day Route: oral Route: steady Dose: 50 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000MedR.pdf Page: p.75	unhealthy, 47 years (range: 18-60 years) n = 345 Health Status: unhealthy Condition: AML Age Group: 47 years (range: 18-60 years) Sex: M+F Population Size: 345 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000MedR.pdf Page: p.75
Nausea	2 patients Disc. AE	50 mg 2 times / day steady, oral Recommended Dose: 50 mg, 2 times / day Route: oral Route: steady Dose: 50 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000MedR.pdf Page: p.75	unhealthy, 47 years (range: 18-60 years) n = 345 Health Status: unhealthy Condition: AML Age Group: 47 years (range: 18-60 years) Sex: M+F Population Size: 345 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000MedR.pdf Page: p.75
Rash	3 patients Disc. AE	50 mg 2 times / day steady, oral Recommended Dose: 50 mg, 2 times / day Route: oral Route: steady Dose: 50 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000MedR.pdf Page: p.75	unhealthy, 47 years (range: 18-60 years) n = 345 Health Status: unhealthy Condition: AML Age Group: 47 years (range: 18-60 years) Sex: M+F Population Size: 345 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000MedR.pdf Page: p.75
Vomiting	3 patients Disc. AE	50 mg 2 times / day steady, oral Recommended Dose: 50 mg, 2 times / day Route: oral Route: steady Dose: 50 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000MedR.pdf Page: p.75	unhealthy, 47 years (range: 18-60 years) n = 345 Health Status: unhealthy Condition: AML Age Group: 47 years (range: 18-60 years) Sex: M+F Population Size: 345 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000MedR.pdf Page: p.75
Transaminases increased	4 patients Disc. AE	50 mg 2 times / day steady, oral Recommended Dose: 50 mg, 2 times / day Route: oral Route: steady Dose: 50 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000MedR.pdf Page: p.75	unhealthy, 47 years (range: 18-60 years) n = 345 Health Status: unhealthy Condition: AML Age Group: 47 years (range: 18-60 years) Sex: M+F Population Size: 345 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000MedR.pdf Page: p.75

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	inhibitor 1767 inducer 389	inhibitor 1852 substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP2A6 707 CYP2B6 810 CYP3A4/5 278 P-gp 1461 BCRP 699 MRP2 383 OATP1B1 788 OATP1B3 706 OAT1 599 OAT3 642	CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2C19 991 CYP2E1 667 CYP3A5 395 CYP1A1 349 CYP3A 191 P-gp 1537 MRP2 205	CYP1A2 701 CYP2B6 547 CYP2C8 168 CYP2C19 293 CYP3A 129 MRP2 111

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	no	CGP52421 1
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	no	CGP62221 1
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	no	CGP52421 1
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	no	CGP62221 1
MRP2 475	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	no	CGP52421 1
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	no
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	no	CGP62221 1
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	no	CGP52421 1
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	no	CGP62221 1
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes [IC50 0.5 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes [IC50 0.5 uM]
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes [IC50 0.5 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes [IC50 1 uM]	CGP62221 1
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes [IC50 1 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes [IC50 1.5 uM]	CGP62221 1
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	yes [IC50 1.5 uM]
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	yes [IC50 1.7 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes [IC50 3 uM]
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	yes [IC50 5 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes [IC50 5 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes [IC50 5 uM]	CGP62221 1
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes [IC50 5 uM]	CGP52421 1
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	yes [IC50 5 uM]
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes	CGP52421 1
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes	CGP62221 1
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes	CGP52421 1
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes	CGP52421 1
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes	CGP62221 1
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes	CGP52421 1
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes	CGP62221 1
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes	CGP52421 1
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes	CGP62221 1
CYP2C8 965	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes
CYP2C8 965	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes	CGP52421 1
CYP2C8 965	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes	CGP62221 1
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes	CGP52421 1
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes	CGP52421 1
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes	CGP62221 1
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes	CGP52421 1
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes	CGP62221 1
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes	CGP52421 1
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes	CGP62221 1
CYP3A 298	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes
CYP3A 298	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes	CGP52421 1
CYP3A 298	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes	CGP62221 1
MRP2 475	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=8 Page: 8.0	yes
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	yes
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	yes	CGP52421 1
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	yes	CGP62221 1
PXR 46	activator 214 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	yes
PXR 46	activator 214 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	yes	CGP52421 1
PXR 46	activator 214 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=32 Page: 32.0	yes	CGP62221 1

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=31 Page: 31.0	major	CGP52421 1
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=31 Page: 31.0	major	CGP62221 1
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=31 Page: 31.0	no
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=31 Page: 31.0	no
CYP2B6 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=31 Page: 31.0	no
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=31 Page: 31.0	no
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=31 Page: 31.0	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=31 Page: 31.0	no
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=31 Page: 31.0	no
CYP3A5 395	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=31 Page: 31.0	no
MRP2 205	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=31 Page: 31.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=31 Page: 31.0	no
CYP1A1 349	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=31 Page: 31.0	yes	CGP52421 1
CYP1A1 349	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=31 Page: 31.0	yes	CGP62221 1
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=31 Page: 31.0	yes	CGP62221 1
CYP3A 191	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=31 Page: 31.0	yes	CGP52421 1
CYP3A 191	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=31 Page: 31.0	yes	CGP62221 1
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=7 Page: 7.0	yes		yes (co-administration study) Comment: Coadministration of ketoconazole (400 mg daily for 10 days) with a single dose of Rydapt (50 mg) on Day 6 increased AUCinf of midostaurin by 10.4-fold and CGP62221 by 3.5-fold and area under the curve over time to last measurable concentrations (AUC0-t) of CGP52421 by 1.2-fold compared to a single Rydapt dose coadministered with placebo. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000ClinPharmR.pdf#page=7 Page: 7.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207997Orig1Orig2s000PharmR.pdf#page=2 Page: 2.0

Sourcing

Vendor/Aggregator	ID	URL
Chem Scene	CS-0014908	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0014908
Compound Cloud	6918236
MedChem Express	HY-19168	https://www.medchemexpress.com/search.html?q=HY-19168&ft=&fa=&fp=
MuseChem	I008642	https://www.musechem.com/product/I008642.html
eMolecules	36772575	https://orderbb.emolecules.com/search/#?query=36772575
mcule	MCULE-6354289466	https://mcule.com/MCULE-6354289466/

PubMed

Title	Date	PubMed
Effects of the N-methyl-D-aspartate receptor antagonist perzinfotel [EAA-090; [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)-ethyl]phosphonic acid] on chemically induced thermal hypersensitivity.	2005 Jun	15764736
Effects of perzinfotel on the minimum alveolar concentration of isoflurane in dogs.	2007 Dec	18052733
Functional identification of NR2 subunits contributing to NMDA receptors on substance P receptor-expressing dorsal horn neurons.	2008 Oct 10	18847474
Effects of intravenous administration of perzinfotel, fentanyl, and a combination of both drugs on the minimum alveolar concentration of isoflurane in dogs.	2009 Dec	19951116
Prodrugs of perzinfotel with improved oral bioavailability.	2009 Feb 12	19146418
Effects of perzinfotel on the minimum alveolar concentration of isoflurane in dogs when administered as a preanesthetic via various routes or in combination with butorphanol.	2010 Jun	20513173
Effects of perzinfotel, butorphanol tartrate, and a butorphanol-perzinfotel combination on the minimum alveolar concentration of isoflurane in cats.	2010 Nov	21034317

Patents

Sample Use Guides

In Vivo Use Guide

30-100 mg/kg orally (rats) 10-30 mg/kg intravenous (dogs)

Route of Administration: Oral

In Vitro Use Guide

IC50 28 nM (inhibited [(3)H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid binding to NMDA receptors). IC50 477 nM (decreased the duration of spontaneous synaptic currents and inhibited NMDA-activated currents in rat hippocampal neurons).

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:31:11 GMT 2023` Edited by `admin` on `Fri Dec 15 16:31:11 GMT 2023`
Record UNII	FX5AUU7Z8T
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

PERZINFOTEL

Official Name

English

EAA-090

Code

English

perzinfotel [INN]

Common Name

English

[2-(8,9-Dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)ethyl]phosphonic acid

Systematic Name

English

PERZINFOTEL [USAN]

Common Name

English

PHOSPHONIC ACID, (2-(8,9-DIOXO-2,6-DIAZABICYCLO(5.2.0)NON-1(7)-EN-2-YL)ETHYL)-

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1509