Identification
- Summary
Talazoparib is a poly-ADP ribose polymerase inhibitor used to treat HER2-, BRCA mutated locally advanced or metastatic breast cancer and HRR gene-mutated metastatic castration-resistant prostate cancer.
- Brand Names
- Talzenna
- Generic Name
- Talazoparib
- DrugBank Accession Number
- DB11760
- Background
Talazoparib is an inhibitor of mammalian polyadenosine 5’-diphosphoribose polymerases (PARPs), enzymes responsible for regulating essential cellular functions, such as DNA transcription and DNA repair.4
Developed by Pfizer, talazoparib was first approved by the FDA in October 2018 2 and by the EMA in June 2019.5 It was approved by Health Canada in September 2020.6 Talazoparib is currently used in the treatment of BRCA-mutated breast cancer and HRR-mutated prostate cancer.4,6,7
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Talazoparib (DB11760)
- Weight
- Average: 380.359
Monoisotopic: 380.119715421 - Chemical Formula
- C19H14F2N6O
- Synonyms
- Talazoparib
- External IDs
- BMN 673
- BMN-673
- BMN673
- LT 006673
- LT-00673
- LT-673
- MDV-3800
Pharmacology
- Indication
Talazoparib is indicated for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer. This indication is approved by the FDA, EMA, and Health Canada.4,6,7
In the US, talazoparib is also indicated in combination with enzalutamide for the treatment of adult patients with HRR gene-mutated metastatic castration-resistant prostate cancer (mCRPC).4
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
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Hrr gene-mutated (hrrm) metastatic castration-resistant prostate cancer (mcrpc) Regimen in combination with: Enzalutamide (DB08899) •••••••••••• ••••• Treatment of Locally advanced breast cancer •••••••••••• ••••• Treatment of Metastatic breast cancer •••••••••••• ••••• - Contraindications & Blackbox Warnings
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Talazoparib is a cytotoxic and anti-tumour agent. In vitro, talazoparib caused cytotoxicity in cancer cell lines that harboured defects in DNA repair genes, including BRCA1 and BRCA2. Talazoparib mediated anti-tumour effects on patient-derived xenograft breast cancer models bearing mutated BRCA1 or mutated BRCA2 or wild type BRCA1 and BRCA2.2,4
- Mechanism of action
Poly(ADP-ribose) polymerases (PARPs) are multifunctional enzymes involved in essential cellular functions, such as DNA transcription and DNA repair. PARPs recognize and repair DNA single-strand breaks (SSBs) via the base excision repair (BER) pathway. DNA double-strand breaks (DSBs) are repaired via homologous recombination by tumour suppressor proteins encoded by BRCA1 and BRCA2.3,2
Talazoparib is a potent inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1 and PARP2.4 In vitro, talazoparib binds to PARP-1 and -2 isoforms with similar affinity.2 Inhibition of the BER pathway by talazoparib leads to the accumulation of unrepaired SSBs, which leads to the formation of DSBs, which is the most toxic form of DNA damage. While BRCA-dependent homologous recombination can repair DSBs in normal cells, this repair pathway is defective in cells with BRCA1/2 mutations, such as certain tumour cells.[A246015] Inhibition of PARP in cancer cells with BRCA mutations leads to genomic instability and apoptotic cell death. This end result is also referred to as synthetic lethality, a phenomenon where the combination of two defects - inhibition of PARP activity and loss of DSB repair by HR - that are otherwise benign when alone leads to detrimental results.1,3 By inhibiting PARP, talazoparib increases the formation of PARP-DNA complexes resulting in DNA damage, decreased cell proliferation, and apoptosis.4
Target Actions Organism APoly [ADP-ribose] polymerase 1 inhibitorHumans APoly [ADP-ribose] polymerase 2 inhibitorHumans - Absorption
After administration of talazoparib 1 mg orally once daily, the mean [% coefficient of variation (CV%)] AUC and maximum observed plasma concentration (Cmax) of talazoparib at steady-state was 208 (37%) ng x hr/mL and 16.4 (32%) ng/mL, respectively. The mean (CV%) steady-state Ctrough was 3.53 (61%) ng/mL.4 Steady state was reached within two to three weeks of therapy.2 The Tmax ranges from one to two hours.4
A high-fat, high-calorie food increased the mean Cmax by 46% and the median Tmax from one to four hours, without affecting the AUC. 4
- Volume of distribution
The mean apparent volume of distribution of talazoparib is 420 L.4
- Protein binding
In vitro, the protein binding of talazoparib is 74% and is independent of talazoparib concentration.4
- Metabolism
Talazoparib undergoes minimal hepatic metabolism. The metabolic pathways include mono-oxidation, dehydrogenation, cysteine conjugation of mono-desfluoro talazoparib, and glucuronide conjugation.4
- Route of elimination
The major route of elimination is renal excretion. Approximately 68.7% of the total administered radiolabeled dose of talazoparib was recovered in urine, where 54.6% of that dose was in the form of an unchanged drug. About 19.7% of the drug was recovered in feces, with 13.6% of the dose is unchanged.4
- Half-life
The mean terminal plasma half-life (±standard deviation) is 90 (±58) hours in patients with cancer.2,4
- Clearance
The mean apparent oral clearance is 6.45 L/h. The inter-subject variability is 31%.4
- Adverse Effects
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There is no information available regarding the acute toxicity (LD50) of talazoparib. There is no specific treatment in the event of talazoparib overdose, and symptoms of overdose have not been established. In the event of an overdose, discontinue treatment with talazoparib, consider gastric decontamination, follow general supportive measures, and treat symptomatically.4
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 The serum concentration of Talazoparib can be increased when it is combined with Abemaciclib. Abrocitinib The serum concentration of Talazoparib can be increased when it is combined with Abrocitinib. Adagrasib The serum concentration of Talazoparib can be increased when it is combined with Adagrasib. Afatinib The serum concentration of Talazoparib can be increased when it is combined with Afatinib. Alectinib The serum concentration of Talazoparib can be increased when it is combined with Alectinib. - Food Interactions
- Take at the same time every day.
- Take with or without food. A high-fat, high-calorie meal decreases Cmax and delays Tmax, but not to a clinically significant extent.
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/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 Talzenna Capsule 0.1 mg/1 Oral Pfizer Laboratories Div Pfizer Inc 2023-06-21 Not applicable US
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
- 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]
- Hoy SM: Talazoparib: First Global Approval. Drugs. 2018 Dec;78(18):1939-1946. doi: 10.1007/s40265-018-1026-z. [Article]
- Bochum S, Berger S, Martens UM: Olaparib. Recent Results Cancer Res. 2018;211:217-233. doi: 10.1007/978-3-319-91442-8_15. [Article]
- FDA Approved Drug Products: TALZENNA (talazoparib) capsules, for oral use (June 2023) [Link]
- Pfizer Press Release: European Commission Approves TALZENNA® (talazoparib) for Patients with Inherited (Germline) BRCA-Mutated Locally Advanced or Metastatic Breast Cancer [Link]
- Health Canada Approved Drug Products: TALZENNA (Talazoparib) Oral Capsules [Link]
- EMA Approved Drug Products: TALZENNA (talazoparib) Oral 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
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment MCRPC 1 3 Active Not Recruiting Treatment Prostate Cancer 1 3 Completed Treatment BRCA 1 Gene Mutation / BRCA 2 Gene Mutation / Breast Neoplasms 1 3 Recruiting Treatment Advanced Malignant Neoplasm / Non-Small Cell Lung Cancer (NSCLC) / Ovarian Cancer / Solid Tumors / Urothelial Cancer 1 3 Terminated Treatment Ovarian Cancer 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 0.1 mg/1 Capsule Oral 0.25 mg/1 Capsule Oral 0.35 mg/1 Capsule Oral 0.5 mg/1 Capsule Oral 0.75 mg/1 Capsule Oral 1 mg/1 Capsule Oral 1.453 mg 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 US10780088 No 2020-09-22 2029-07-27 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 splash10-001i-0009000000-1eff4346bf91d0ab9a06 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-056r-0009000000-d6852a92f125c7601cbd Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-0009000000-ae3f4f2e7eed281bfe79 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-0009000000-ba83b1b6b5be43e9cf9d Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-01ti-0069000000-89f9f29acfc5ca983f20 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-002r-3349000000-673477b0c4c2c7f71c47 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 194.31976 predictedDeepCCS 1.0 (2019) [M+H]+ 196.71535 predictedDeepCCS 1.0 (2019) [M+Na]+ 202.62785 predictedDeepCCS 1.0 (2019)
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]
- FDA Approved Drug Products: TALZENNA (talazoparib) capsules, for oral use (June 2023) [Link]
- 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]
- FDA Approved Drug Products: TALZENNA (talazoparib) capsules, for oral use (June 2023) [Link]
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
References
- Bruin MAC, Sonke GS, Beijnen JH, Huitema ADR: Pharmacokinetics and Pharmacodynamics of PARP Inhibitors in Oncology. Clin Pharmacokinet. 2022 Dec;61(12):1649-1675. doi: 10.1007/s40262-022-01167-6. Epub 2022 Oct 11. [Article]
- Elmeliegy M, Lang I, Smolyarchuk EA, Chung CH, Plotka A, Shi H, Wang D: Evaluation of the effect of P-glycoprotein inhibition and induction on talazoparib disposition in patients with advanced solid tumours. Br J Clin Pharmacol. 2020 Apr;86(4):771-778. doi: 10.1111/bcp.14178. Epub 2020 Jan 7. [Article]
- FDA Approved Drug Products: TALZENNA (talazoparib) capsules, for oral use (June 2023) [Link]
- 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
References
- Bruin MAC, Sonke GS, Beijnen JH, Huitema ADR: Pharmacokinetics and Pharmacodynamics of PARP Inhibitors in Oncology. Clin Pharmacokinet. 2022 Dec;61(12):1649-1675. doi: 10.1007/s40262-022-01167-6. Epub 2022 Oct 11. [Article]
- Elmeliegy M, Lang I, Smolyarchuk EA, Chung CH, Plotka A, Shi H, Wang D: Evaluation of the effect of P-glycoprotein inhibition and induction on talazoparib disposition in patients with advanced solid tumours. Br J Clin Pharmacol. 2020 Apr;86(4):771-778. doi: 10.1111/bcp.14178. Epub 2020 Jan 7. [Article]
- FDA Approved Drug Products: TALZENNA (talazoparib) capsules, for oral use (June 2023) [Link]
Drug created at October 20, 2016 20:45 / Updated at July 18, 2023 22:56