TALAZOPARIB

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H14F2N6O
Molecular Weight	380.3509
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CN1N=CN=C1[C@@H]2[C@H](NC3=CC(F)=CC4=C3C2=NNC4=O)C5=CC=C(F)C=C5

InChI

InChIKey=HWGQMRYQVZSGDQ-HZPDHXFCSA-N

InChI=1S/C19H14F2N6O/c1-27-18(22-8-23-27)15-16(9-2-4-10(20)5-3-9)24-13-7-11(21)6-12-14(13)17(15)25-26-19(12)28/h2-8,15-16,24H,1H3,(H,26,28)/t15-,16-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C19H14F2N6O
Molecular Weight	380.3509
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

BMN-673 (8R,9S) is the (8R,9S) enantiomer of BMN-673, known as talazoparib. BMN 673 is a novel inhibitor of nuclear enzyme poly (ADP-ribose) polymerase (PARP) with potential antineoplastic activity.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Poly [ADP-ribose] polymerase-1 23	Inhibitor 8,504		1.2 nM [Ki]
Poly [ADP-ribose] polymerase 2 16	Inhibitor 8,504		0.87 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Unknown 2,596
Breast cancer 432	Primary	Approved 8,583	TALZENNA
Ovarian cancer 160	Primary	Phase III 665	Unknown

C_max

Value	Dose	Analyte	Population
9.97 ng/mL	1 mg single, oral	TALAZOPARIB plasma	Homo sapiens
19.8 ng/mL	1 mg 1 times / day steady-state, oral	TALAZOPARIB plasma	Homo sapiens
16.4 ng/mL	1 mg 1 times / day steady-state, oral	TALAZOPARIB plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
193 ng × h/mL	1 mg single, oral	TALAZOPARIB plasma	Homo sapiens
196 ng × h/mL	1 mg 1 times / day steady-state, oral	TALAZOPARIB plasma	Homo sapiens
208 ng × h/mL	1 mg 1 times / day steady-state, oral	TALAZOPARIB plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
90 h	1 mg 1 times / day steady-state, oral		TALAZOPARIB plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
26%	1 mg 1 times / day steady-state, oral		TALAZOPARIB plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
1 mg 1 times / day steady, oral Recommended	unhealthy, 31 - 75 years	Disc. AE: Anemia, Function liver abnormal... Other AEs: Myelosuppression...
1.1 mg 1 times / day multiple, oral MTD	unhealthy, unknown	Disc. AE: Thrombocytopenia, Thrombocytopenia...
1 mg 1 times / day multiple, oral Recommended	unhealthy, unknown	Other AEs: Decreased hemoglobin, Leukocyte count decreased...
1 mg 1 times / day multiple, oral Recommended	unhealthy, unknown	Disc. AE: Anemia, Accidental overdose...
1 mg 1 times / day multiple, oral Recommended	unhealthy, unknown	Other AEs: Anemia, Neutropenia...

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AEs

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AE	Significance	Dose	Population
Anemia	1 patient Disc. AE	1 mg 1 times / day steady, oral Recommended	unhealthy, 31 - 75 years
Function liver abnormal	2 patients Disc. AE	1 mg 1 times / day steady, oral Recommended	unhealthy, 31 - 75 years
Myelosuppression	23 patients	1 mg 1 times / day steady, oral Recommended	unhealthy, 31 - 75 years
Thrombocytopenia	grade 3, 16.67% Disc. AE	1.1 mg 1 times / day multiple, oral MTD	unhealthy, unknown
Thrombocytopenia	grade 4, 16.67% Disc. AE	1.1 mg 1 times / day multiple, oral MTD	unhealthy, unknown

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1,087	inhibitor 2,438	inhibitor 2,507	inhibitor 2,217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2,153 CYP2B6 926 CYP2C8 1,057 CYP2C19 2,057 CYP3A4/5 296 UGT1A1 246 UGT1A4 98 UGT1A6 136 UGT1A9 148 UGT2B7 197 UGT2B15 84 BSEP 550	P-gp 2,052 BCRP 697 OAT1 395 OAT3 391 OCT1 393 OCT2 434 OATP1B1 503 OATP1B3 435 MATE1 182 MATE2 98 BSEP 63 hepatic enzymes 2	CYP1A2 832 CYP2B6 669

Drug as perpetrator

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Target	Modality	Activity
BSEP 554	inhibitor 4,027	no
CYP1A2 2,333	inducer 1,966	no
CYP1A2 2,333	inhibitor 4,027	no
CYP2B6 1,160	inducer 1,966	no
CYP2B6 1,160	inhibitor 4,027	no

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Drug as victim

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Target	Modality	Activity
hepatic enzymes 2	substrate 4,014	minor
BSEP 63	substrate 4,014	no
MATE1 182	substrate 4,014	no
MATE2 98	substrate 4,014	no
OAT1 395	substrate 4,014	no

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2,263	inhibitor 2,237

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
AbMole Bioscience	1732	http://www.abmole.com/product.asp?id=1732
AbMole Bioscience	M1732	http://www.abmole.com/products/bmn673.html
Achemtek	0102-014244	http://www.achemtek.com/1207456-01-6
Acorn PharmaTech	ACN-053048	http://www.acornpharmatech.com/
AK Scientific, Inc. (AKSCI)	X5821	http://www.aksci.com/item_detail.php?cat=X5821

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PubMed

Title	Date	PubMed
No data available in table

Patents

Sample Use Guides

In Vivo Use Guide

Signs of activity of talazoparib were observed at 100 µg/day doses, and the maximum tolerated dose was 1.0 mg/day

Route of Administration: Oral

In Vitro Use Guide

Talazoparib (BMN 673) induces DNA damage at picomolar concentrations

Substance Class	Chemical
Record UNII	9QHX048FRV
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

talazoparib [INN]

Preferred Name

English

TALAZOPARIB

Official Name

English

BMN 673

Code

English

3H-PYRIDO(4,3,2-DE)PHTHALAZIN-3-ONE, 5-FLUORO-8-(4-FLUOROPHENYL)-2,7,8,9-TETRAHYDRO-9-(1-METHYL-1H-1,2,4-TRIAZOL-5-YL)-, (8S,9R)-

Systematic Name

English

TALAZOPARIB [USAN]

Common Name

English

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Classification Tree

Code System

Code

Enzyme Inhibitor

NCI_THESAURUS

C62554

Other antineoplastic agents

WHO-ATC

L01XX60

Established Pharmacologic Class

NDF-RT

N0000191623

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Code System

Code

Type

Description

USAN

BC-63

PRIMARY

DAILYMED

9QHX048FRV

PRIMARY

RXCUI

2099704

PRIMARY

CAS

1207456-01-6

PRIMARY

FDA UNII

9QHX048FRV

PRIMARY

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Related Record

Type

Details


					6D53G0FD0Z

PLASMA PROTEIN FRACTION (HUMAN)

BINDER->LIGAND

Comments:

In vitro, protein binding of talazoparib is 74% and is independent of talazoparib concentration.

Interaction Type:

BINDING

Amount:

74 % (average)


					02WK9U5NZC

TALAZOPARIB TOSYLATE

SALT/SOLVATE -> PARENT

Amount:


					76UB6O122H

ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 2

TRANSPORTER -> SUBSTRATE

Comments:

Co-administration with BCRP inhibitors may increase talazoparib exposure.


					22ES734693

MULTIDRUG RESISTANCE PROTEIN 1

TRANSPORTER -> SUBSTRATE

Comments:

Co-administration of talazoparib with certain P-gp inhibitors including amiodarone, carvedilol, clarithromycin, itraconazole, and verapamil in the clinical studies (PRP-001, PRP-002, ABRAZO and EMBRACA) increased talazoparib exposure by 44.7%, in conjunction with an increased rate of Talzenna dose reductions (41%).


					9QHX048FRV

TALAZOPARIB

EXCRETED UNCHANGED

Qualification:

FECAL

Amount:

54.6 % (average)

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Related Record

Type

Details


					9QHX048FRV

TALAZOPARIB

ACTIVE MOIETY

Amount:

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Name	Property Type	Amount
Tmax	PHARMACOKINETIC	[1 to 2] hours (average)

Biological Half-life	PHARMACOKINETIC	90 hours (average)

Volume of Distribution	PHARMACOKINETIC	420 LITERS (average)

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator