Identification
- Summary
Talazoparib is a poly-ADP ribose polymerase inhibitor used to treat HER2-, BRCA mutated locally advanced or metastatic breast cancer.
- Brand Names
- Talzenna
- Generic Name
- Talazoparib
- DrugBank Accession Number
- DB11760
- Background
Talazoparib was approved by the FDA for use in germline BRCA mutated, HER2 negative, locally advanced or metastatic breast cancer on October 16, 2018 under the trade name Talzenna 3. Talzenna was granted approval based on the results of the EMBRACA trial in which talazoparib resulted in a mean 8.6 months progression-free survival time versus physician's choice chemotherapy which resulted in 5.6 months progression-free survival.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 380.359
Monoisotopic: 380.119715421 - Chemical Formula
- C19H14F2N6O
- Synonyms
- Talazoparib
- External IDs
- BMN 673
- BMN-673
- LT-673
Pharmacology
- Indication
Talazoparib is indicated for the treatment of deleterious or suspected deleterious germline BRCA mutated, HER2 negative locally advanced or metastatic breast cancer in adults Label.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
- Contraindications & Blackbox Warnings
- Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.
- Pharmacodynamics
Talazoparib prevents PARP-mediated repair of DNA damage in cancer cells, allowing accumulation of damage and PARP-DNA complexes Label. Repair related errors by error prone secondary repair pathways may also contribute to the cytotoxicity of talazoparib 2.
- Mechanism of action
Talazoparib binds to and inhibits PARP1 and PARP2 at the NAD+ binding site with a Ki of 1.2 and 0.87 nM, respectively 1. The inhibitory effect on PAR synthesis has an EC50 of 2.51 nM.
Target Actions Organism APoly [ADP-ribose] polymerase 1 inhibitorHumans APoly [ADP-ribose] polymerase 2 inhibitorHumans - Absorption
Talzenna capsules have a reach peak plasma concentration in 1-2 h Label. If taken with a high fat meal, Cmax decreases by 43%, Tmax increases by 1-4 h, and no change occurs in AUC.
- Volume of distribution
Talazoparib has a mean apparent volume of distribution of 420 L Label.
- Protein binding
Talazoparib is 74% bound to plasma proteins and independent of drug concentration Label.
- Metabolism
Talazoparib is metabolized via mono-oxidation, dehydrogenation, cysteine conjugation of a mono-desfluoro metabolite, and glucuronide conjugation Label. The overall contribution of metabolism to talazoparib elimination is minimal.
- Route of elimination
64.7% of talazoparib is excreted in the urine with 54.6% as unchanged drug Label. 19.7% is eliminated in the feces with 13.6% as unchanged drug.
- Half-life
The mean terminal plasma half life of Talzenna capsules is 90 h with a standard deviation of 58 h Label.
- Clearance
The mean apparent oral clearance of talazoparib is 6.45 L/h with an inter-individual variability of 31.1% Label. Apparent oral clearance is reduced by 14.4% in patients with mild renal impairment while mild hepatic impairment has no effect. No data is available in patients with moderate to severe renal or hepatic impairment.
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Talazoparib is clastogenic due to its pharmacological mechanism Label. Talazoparib does not appear to be mutagenic and no data is available on carcinogenicity.
In repeat-dose toxicity studies up to 3-months duration at doses ≥0.04 mg/kg/day in rats and ≥0.01 mg/kg/day in dogs resulted in decreased organ weights, luminal cellular debris, reduced sperm, and degeneration/atrophy in the testis and epididymis Label. These doses were equivalent to approximately 1.0 times and 0.2 times normal human exposure. Follicular atresia of the ovary was observed in rats at doses ≥1 mg/kg/day, equivalent to 9.5 times normal human exposure. While no fertility data exists these results suggest a potential for reduced fertility due to talazoparib exposure.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbemaciclib Abemaciclib may decrease the excretion rate of Talazoparib which could result in a higher serum level. Abrocitinib The serum concentration of Talazoparib can be increased when it is combined with Abrocitinib. Afatinib The serum concentration of Talazoparib can be increased when it is combined with Afatinib. Alectinib Alectinib may decrease the excretion rate of Talazoparib which could result in a higher serum level. Ambrisentan The serum concentration of Talazoparib can be increased when it is combined with Ambrisentan. Amiodarone The serum concentration of Talazoparib can be increased when it is combined with Amiodarone. Apalutamide The serum concentration of Talazoparib can be decreased when it is combined with Apalutamide. Apixaban The serum concentration of Talazoparib can be increased when it is combined with Apixaban. Arsenic trioxide The serum concentration of Talazoparib can be increased when it is combined with Arsenic trioxide. Articaine The risk or severity of methemoglobinemia can be increased when Talazoparib is combined with Articaine. Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - Food Interactions
- Take at the same time every day.
- Take with or without food.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Talazoparib tosylate 02WK9U5NZC 1373431-65-2 QUQKKHBYEFLEHK-QNBGGDODSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Talzenna Capsule 1 mg Oral Pfizer Canada Ulc Not applicable Not applicable Canada Talzenna Capsule 0.5 mg/1 Oral Pfizer Laboratories Div Pfizer Inc 2022-01-31 Not applicable US Talzenna Capsule 1 mg/1 Oral Excella GmbH & Co. KG 2018-10-26 Not applicable US Talzenna Capsule 1 mg Oral Pfizer Europe Ma Eeig 2021-02-11 Not applicable EU Talzenna Capsule 0.25 mg Oral Pfizer Europe Ma Eeig 2021-02-11 Not applicable EU Talzenna Capsule 0.25 mg Oral Pfizer Canada Ulc Not applicable Not applicable Canada Talzenna Capsule 1 mg/1 Oral Pfizer Laboratories Div Pfizer Inc 2018-10-26 Not applicable US Talzenna Capsule 0.25 mg/1 Oral Excella GmbH & Co. KG 2018-10-26 Not applicable US Talzenna Capsule 0.25 mg Oral Pfizer Europe Ma Eeig 2021-02-11 Not applicable EU Talzenna Capsule 0.25 mg Oral Pfizer Europe Ma Eeig 2021-02-11 Not applicable EU
Categories
- ATC Codes
- L01XK04 — Talazoparib
- Drug Categories
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Substrates
- Enzyme Inhibitors
- Narrow Therapeutic Index Drugs
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Poly (ADP-ribose) polymerase (PARP) inhibitors
- Poly(ADP-ribose) Polymerase Inhibitors
- Pyridazines
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylquinolines. These are heterocyclic compounds containing a quinoline moiety substituted with a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Quinolines and derivatives
- Sub Class
- Phenylquinolines
- Direct Parent
- Phenylquinolines
- Alternative Parents
- Phthalazinones / Secondary alkylarylamines / Pyridazinones / Fluorobenzenes / Aralkylamines / Aryl fluorides / Triazoles / Heteroaromatic compounds / Lactams / Azacyclic compounds show 4 more
- Substituents
- 1,2,4-triazole / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Azole / Benzenoid / Fluorobenzene show 19 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 9QHX048FRV
- CAS number
- 1207456-01-6
- InChI Key
- HWGQMRYQVZSGDQ-HZPDHXFCSA-N
- InChI
- 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
- IUPAC Name
- (11S,12R)-7-fluoro-11-(4-fluorophenyl)-12-(1-methyl-1H-1,2,4-triazol-5-yl)-2,3,10-triazatricyclo[7.3.1.0^{5,13}]trideca-1,5,7,9(13)-tetraen-4-one
- SMILES
- CN1N=CN=C1[C@@H]1[C@H](NC2=C3C1=NNC(=O)C3=CC(F)=C2)C1=CC=C(F)C=C1
References
- Synthesis Reference
Wang B, Chu D, Feng Y, Shen Y, Aoyagi-scharber M, Post LE. Discovery and Characterization of (8S,9R)-5-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-3-one (BMN 673, Talazoparib), a Novel, Highly Potent, and Orally Efficacious Poly(ADP-ribose) Polymerase-1/2 Inhibitor, as an Anticancer Agent. J Med Chem. 2016;59(1):335-57.
- General References
- Wang B, Chu D, Feng Y, Shen Y, Aoyagi-Scharber M, Post LE: Discovery and Characterization of (8S,9R)-5-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-te trahydro-3H-pyrido[4,3,2-de]phthalazin-3-one (BMN 673, Talazoparib), a Novel, Highly Potent, and Orally Efficacious Poly(ADP-ribose) Polymerase-1/2 Inhibitor, as an Anticancer Agent. J Med Chem. 2016 Jan 14;59(1):335-57. doi: 10.1021/acs.jmedchem.5b01498. Epub 2015 Dec 23. [Article]
- Javle M, Curtin NJ: The role of PARP in DNA repair and its therapeutic exploitation. Br J Cancer. 2011 Oct 11;105(8):1114-22. doi: 10.1038/bjc.2011.382. [Article]
- Talazoparib FDA Approval [Link]
- FDA Approved Drug Products: TALZENNA (talazoparib) capsules [Link]
- External Links
- PubChem Compound
- 44819241
- PubChem Substance
- 347828114
- ChemSpider
- 28637772
- BindingDB
- 50084621
- 2099704
- ChEMBL
- CHEMBL3137320
- ZINC
- ZINC000072318110
- PDBe Ligand
- 2YQ
- Wikipedia
- Talazoparib
- PDB Entries
- 4pjt / 4pjv / 4und / 7kk3 / 7kkn
- FDA label
- Download (549 KB)
- MSDS
- Download (25 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 0.25 mg/1 Capsule Oral 0.5 mg/1 Capsule Oral 0.75 mg/1 Capsule Oral 1 mg/1 Capsule Oral 0.25 mg Capsule Oral 1 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9820985 No 2017-11-21 2029-07-27 US US8012976 No 2011-09-06 2029-10-19 US US8735392 No 2014-05-27 2031-10-20 US US8420650 No 2013-04-16 2029-07-27 US US10189837 No 2019-01-29 2031-10-20 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.101 mg/mL ALOGPS logP 2.93 ALOGPS logP 2.11 Chemaxon logS -3.6 ALOGPS pKa (Strongest Acidic) 9.48 Chemaxon pKa (Strongest Basic) 1.66 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 84.2 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 111.27 m3·mol-1 Chemaxon Polarizability 35.82 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets

- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This ...
- Gene Name
- PARP1
- Uniprot ID
- P09874
- Uniprot Name
- Poly [ADP-ribose] polymerase 1
- Molecular Weight
- 113082.945 Da
References
- Wang B, Chu D, Feng Y, Shen Y, Aoyagi-Scharber M, Post LE: Discovery and Characterization of (8S,9R)-5-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-te trahydro-3H-pyrido[4,3,2-de]phthalazin-3-one (BMN 673, Talazoparib), a Novel, Highly Potent, and Orally Efficacious Poly(ADP-ribose) Polymerase-1/2 Inhibitor, as an Anticancer Agent. J Med Chem. 2016 Jan 14;59(1):335-57. doi: 10.1021/acs.jmedchem.5b01498. Epub 2015 Dec 23. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Nad+ adp-ribosyltransferase activity
- Specific Function
- Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This ...
- Gene Name
- PARP2
- Uniprot ID
- Q9UGN5
- Uniprot Name
- Poly [ADP-ribose] polymerase 2
- Molecular Weight
- 66205.31 Da
References
- Wang B, Chu D, Feng Y, Shen Y, Aoyagi-Scharber M, Post LE: Discovery and Characterization of (8S,9R)-5-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-te trahydro-3H-pyrido[4,3,2-de]phthalazin-3-one (BMN 673, Talazoparib), a Novel, Highly Potent, and Orally Efficacious Poly(ADP-ribose) Polymerase-1/2 Inhibitor, as an Anticancer Agent. J Med Chem. 2016 Jan 14;59(1):335-57. doi: 10.1021/acs.jmedchem.5b01498. Epub 2015 Dec 23. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
Drug created at October 20, 2016 20:45 / Updated at August 19, 2021 10:28