Peringatan Keamanan

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.^L47236

Talazoparib

DB11760

small molecule approved investigational

Deskripsi

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.^L47236

Developed by Pfizer, talazoparib was first approved by the FDA in October 2018 ^A260346 and by the EMA in June 2019.^L47296 It was approved by Health Canada in September 2020.^L47301 Talazoparib is currently used in the treatment of BRCA-mutated breast cancer and HRR-mutated prostate cancer.L47236, L47301, L47306

Struktur Molekul 2D

Berat 380.359

Wujud solid

Peta Jejaring Molekuler

Obat Target Gen Interaksi Enzim Transporter Carrier

Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

1. Pendahuluan & Konsep

Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).

2. Sumber Data (Validasi)

Data Obat: Diekstraksi dari elemen drugbank-id dan name pada skema XML DrugBank.
Target Protein: Diambil dari elemen targets/target yang memuat polipeptida sasaran.
Genetik: Disinkronisasi dari sub-elemen gene-name dan varian snp-effects.
Genetik: Jumlah titik node dibatasi pada maksimal 10 (Slice=10) interaksi untuk menghindari tumpukan data.

3. Algoritma Visualisasi

Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.

4. Legenda Visual

Obat Utama (Pusat Analisis)

Target Protein (Mekanisme)

Gen (Faktor Genetik)

Metode ini mendukung analisis Precision Medicine dan evaluasi risiko Drug-Drug Interaction (DDI).

Profil Farmakokinetik

Waktu Paruh (Half-Life) The mean terminal plasma half-life (±standard deviation) is 90 (±58) hours in patients with cancer.[A260346, L47236]

Volume Distribusi The mean apparent volume of distribution of talazoparib is 420 L.[L47236]

Klirens (Clearance) The mean apparent oral clearance is 6.45 L/h. The inter-subject variability is 31%.[L47236]

Absorpsi

After administration of talazoparib 1 mg orally once daily, the mean % coefficient of variation (CV%) AUC and maximum observed plasma concentration (C_max) of talazoparib at steady-state was 208 (37%) ng x hr/mL and 16.4 (32%) ng/mL, respectively. The mean (CV%) steady-state C_trough was 3.53 (61%) ng/mL.^L47236 Steady state was reached within two to three weeks of therapy.^A260346 The T_max ranges from one to two hours.^L47236 A high-fat, high-calorie food increased the mean C_max by 46% and the median T_max from one to four hours, without affecting the AUC. ^L47236

Metabolisme

Talazoparib undergoes minimal hepatic metabolism. The metabolic pathways include mono-oxidation, dehydrogenation, cysteine conjugation of mono-desfluoro talazoparib, and glucuronide conjugation.^L47236

Rute Eliminasi

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.^L47236

Interaksi Makanan

2 Data

1. Take at the same time every day.
2. Take with or without food. A high-fat, high-calorie meal decreases Cmax and delays Tmax, but not to a clinically significant extent.

Interaksi Obat

337 Data

Ranolazine	The serum concentration of Talazoparib can be increased when it is combined with Ranolazine.
Lumacaftor	The serum concentration of Talazoparib can be increased when it is combined with Lumacaftor.
Vemurafenib	The serum concentration of Talazoparib can be increased when it is combined with Vemurafenib.
Apalutamide	The serum concentration of Talazoparib can be decreased when it is combined with Apalutamide.
Pitolisant	The serum concentration of Talazoparib can be increased when it is combined with Pitolisant.
Isavuconazole	The serum concentration of Talazoparib can be increased when it is combined with Isavuconazole.
Isavuconazonium	The serum concentration of Talazoparib can be increased when it is combined with Isavuconazonium.
Pravastatin	The serum concentration of Talazoparib can be increased when it is combined with Pravastatin.
Diethylstilbestrol	The serum concentration of Talazoparib can be increased when it is combined with Diethylstilbestrol.
Estradiol	The serum concentration of Talazoparib can be increased when it is combined with Estradiol.
Sulfasalazine	The serum concentration of Talazoparib can be increased when it is combined with Sulfasalazine.
Novobiocin	The serum concentration of Talazoparib can be increased when it is combined with Novobiocin.
Hesperetin	The serum concentration of Talazoparib can be increased when it is combined with Hesperetin.
Rabeprazole	The serum concentration of Talazoparib can be increased when it is combined with Rabeprazole.
Dexamethasone	The serum concentration of Talazoparib can be increased when it is combined with Dexamethasone.
Dasatinib	The serum concentration of Talazoparib can be increased when it is combined with Dasatinib.
Topiroxostat	The serum concentration of Talazoparib can be increased when it is combined with Topiroxostat.
Daidzin	The serum concentration of Talazoparib can be increased when it is combined with Daidzin.
Fusidic acid	The serum concentration of Talazoparib can be increased when it is combined with Fusidic acid.
Naringenin	The serum concentration of Talazoparib can be increased when it is combined with Naringenin.
Eltrombopag	The serum concentration of Talazoparib can be increased when it is combined with Eltrombopag.
Safinamide	The serum concentration of Talazoparib can be increased when it is combined with Safinamide.
Vismodegib	The serum concentration of Talazoparib can be increased when it is combined with Vismodegib.
Teriflunomide	The serum concentration of Talazoparib can be increased when it is combined with Teriflunomide.
Dabrafenib	The serum concentration of Talazoparib can be increased when it is combined with Dabrafenib.
Cannabidiol	The serum concentration of Talazoparib can be increased when it is combined with Cannabidiol.
Dasabuvir	The serum concentration of Talazoparib can be increased when it is combined with Dasabuvir.
Fostamatinib	The serum concentration of Talazoparib can be increased when it is combined with Fostamatinib.
Gilteritinib	The serum concentration of Talazoparib can be increased when it is combined with Gilteritinib.
Brigatinib	The serum concentration of Talazoparib can be increased when it is combined with Brigatinib.
Estradiol acetate	The serum concentration of Talazoparib can be increased when it is combined with Estradiol acetate.
Estradiol benzoate	The serum concentration of Talazoparib can be increased when it is combined with Estradiol benzoate.
Estradiol cypionate	The serum concentration of Talazoparib can be increased when it is combined with Estradiol cypionate.
Estradiol dienanthate	The serum concentration of Talazoparib can be increased when it is combined with Estradiol dienanthate.
Estradiol valerate	The serum concentration of Talazoparib can be increased when it is combined with Estradiol valerate.
Nabiximols	The serum concentration of Talazoparib can be increased when it is combined with Nabiximols.
Caffeine	The serum concentration of Talazoparib can be increased when it is combined with Caffeine.
Pantoprazole	The serum concentration of Talazoparib can be increased when it is combined with Pantoprazole.
Nelfinavir	The serum concentration of Talazoparib can be increased when it is combined with Nelfinavir.
Gefitinib	The serum concentration of Talazoparib can be increased when it is combined with Gefitinib.
Beclomethasone dipropionate	The serum concentration of Talazoparib can be increased when it is combined with Beclomethasone dipropionate.
Progesterone	The serum concentration of Talazoparib can be increased when it is combined with Progesterone.
Lansoprazole	The serum concentration of Talazoparib can be increased when it is combined with Lansoprazole.
Imatinib	The serum concentration of Talazoparib can be increased when it is combined with Imatinib.
Buprenorphine	The serum concentration of Talazoparib can be increased when it is combined with Buprenorphine.
Telmisartan	The serum concentration of Talazoparib can be increased when it is combined with Telmisartan.
Sunitinib	The serum concentration of Talazoparib can be increased when it is combined with Sunitinib.
Genistein	The serum concentration of Talazoparib can be increased when it is combined with Genistein.
Quercetin	The serum concentration of Talazoparib can be increased when it is combined with Quercetin.
Rilpivirine	The serum concentration of Talazoparib can be increased when it is combined with Rilpivirine.
Alectinib	The serum concentration of Talazoparib can be increased when it is combined with Alectinib.
Abemaciclib	The serum concentration of Talazoparib can be increased when it is combined with Abemaciclib.
Erlotinib	The serum concentration of Talazoparib can be increased when it is combined with Erlotinib.
Taurocholic acid	The serum concentration of Talazoparib can be increased when it is combined with Taurocholic acid.
Dovitinib	The serum concentration of Talazoparib can be increased when it is combined with Dovitinib.
Paritaprevir	The serum concentration of Talazoparib can be increased when it is combined with Paritaprevir.
Fostemsavir	The serum concentration of Talazoparib can be increased when it is combined with Fostemsavir.
Avanafil	The serum concentration of Talazoparib can be increased when it is combined with Avanafil.
Tivozanib	The serum concentration of Talazoparib can be increased when it is combined with Tivozanib.
Cholesterol	Cholesterol may increase the excretion rate of Talazoparib which could result in a lower serum level and potentially a reduction in efficacy.
Venlafaxine	Venlafaxine may increase the excretion rate of Talazoparib which could result in a lower serum level and potentially a reduction in efficacy.
Levothyroxine	The serum concentration of Talazoparib can be decreased when it is combined with Levothyroxine.
Trazodone	The serum concentration of Talazoparib can be decreased when it is combined with Trazodone.
Rifampin	The serum concentration of Talazoparib can be decreased when it is combined with Rifampicin.
St. John's Wort	The serum concentration of Talazoparib can be decreased when it is combined with St. John's Wort.
Prednisolone phosphate	The serum concentration of Talazoparib can be decreased when it is combined with Prednisolone phosphate.
Dexamethasone acetate	The serum concentration of Talazoparib can be increased when it is combined with Dexamethasone acetate.
Vandetanib	The serum concentration of Talazoparib can be increased when it is combined with Vandetanib.
Palbociclib	The serum concentration of Talazoparib can be increased when it is combined with Palbociclib.
Dacomitinib	The serum concentration of Talazoparib can be increased when it is combined with Dacomitinib.
Glasdegib	The serum concentration of Talazoparib can be increased when it is combined with Glasdegib.
Fluconazole	The serum concentration of Talazoparib can be increased when it is combined with Fluconazole.
Erythromycin	The serum concentration of Talazoparib can be increased when it is combined with Erythromycin.
Sildenafil	The serum concentration of Talazoparib can be increased when it is combined with Sildenafil.
Reserpine	The serum concentration of Talazoparib can be increased when it is combined with Reserpine.
Sorafenib	The serum concentration of Talazoparib can be increased when it is combined with Sorafenib.
Loxapine	The serum concentration of Talazoparib can be increased when it is combined with Loxapine.
Quinine	The serum concentration of Talazoparib can be increased when it is combined with Quinine.
Ritonavir	The serum concentration of Talazoparib can be increased when it is combined with Ritonavir.
Toremifene	The serum concentration of Talazoparib can be increased when it is combined with Toremifene.
Verapamil	The serum concentration of Talazoparib can be increased when it is combined with Verapamil.
Tamoxifen	The serum concentration of Talazoparib can be increased when it is combined with Tamoxifen.
Mifepristone	The serum concentration of Talazoparib can be increased when it is combined with Mifepristone.
Vardenafil	The serum concentration of Talazoparib can be increased when it is combined with Vardenafil.
Tacrolimus	The serum concentration of Talazoparib can be increased when it is combined with Tacrolimus.
Conivaptan	The serum concentration of Talazoparib can be increased when it is combined with Conivaptan.
Quinidine	The serum concentration of Talazoparib can be increased when it is combined with Quinidine.
Zonisamide	The serum concentration of Talazoparib can be increased when it is combined with Zonisamide.
Tipranavir	The serum concentration of Talazoparib can be increased when it is combined with Tipranavir.
Ketoconazole	The serum concentration of Talazoparib can be increased when it is combined with Ketoconazole.
Amiodarone	The serum concentration of Talazoparib can be increased when it is combined with Amiodarone.
Carvedilol	The serum concentration of Talazoparib can be increased when it is combined with Carvedilol.
Itraconazole	The serum concentration of Talazoparib can be increased when it is combined with Itraconazole.
Propafenone	The serum concentration of Talazoparib can be increased when it is combined with Propafenone.
Clarithromycin	The serum concentration of Talazoparib can be increased when it is combined with Clarithromycin.
Saquinavir	The serum concentration of Talazoparib can be increased when it is combined with Saquinavir.
Lapatinib	The serum concentration of Talazoparib can be increased when it is combined with Lapatinib.
Paliperidone	The serum concentration of Talazoparib can be increased when it is combined with Paliperidone.
Mibefradil	The serum concentration of Talazoparib can be increased when it is combined with Mibefradil.
Lopinavir	The serum concentration of Talazoparib can be increased when it is combined with Lopinavir.

Target Protein

Poly [ADP-ribose] polymerase 1 PARP1

Poly [ADP-ribose] polymerase 2 PARP2

Referensi & Sumber

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-pyrido4,3,2-dephthalazin-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.

Artikel (PubMed)

PMID: 21989215
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.
PMID: 30506138
Hoy SM: Talazoparib: First Global Approval. Drugs. 2018 Dec;78(18):1939-1946. doi: 10.1007/s40265-018-1026-z.
PMID: 30069770
Bochum S, Berger S, Martens UM: Olaparib. Recent Results Cancer Res. 2018;211:217-233. doi: 10.1007/978-3-319-91442-8_15.

Link

Contoh Produk & Brand

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Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.