Peringatan Keamanan

There are no data regarding overdosage with inavolisib.

Inavolisib

DB15275

small molecule approved investigational

Deskripsi

PIK3CA is one of the most frequently mutated oncogenes, with the resulting mutated p110? protein it encodes playing a central role in tumor cell proliferation.^A264563 Chemotherapeutic agents targeting the PI3K p110? catalytic subunit have shown antitumor activity and a manageable safety profile - some of which are in clinical use, like alpelisib - but preclinical studies have shown that PI3K pathway inhibition releases negative feedback and activates receptor tyrosine kinase signaling, reengaging the pathway and attenuating drug activity.^A264563 Newer PI3K inhibitors, like inavolisib, seek to mitigate this attenuation.

Inavolisib is an inhibitor of PI3K? that was approved by the FDA in October 2024 for the treatment of certain patients with advanced breast cancers.L51748,L51738

Struktur Molekul 2D

Berat 407.378

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 elimination half-life of inavolisib is 15 hours.[L51738]

Volume Distribusi The apparent volume of distribution of inavolisib is 155 liters.[L51738]

Klirens (Clearance) The total clearance of inavolisib is 8.8 L/h.[L51738]

Absorpsi

The absolute oral bioavailability of inavolisib is 76%.^L51738 At steady-state - attained by approximately day 5 - the AUC and C_max of inavolisib are 1010 h*ng/mL and 69 ng/mL, respectively.^L51738 The time to maximum plasma concentration (T_max) at steady-state is 3 hours.^L51738

Metabolisme

Inavolisib is primarily metabolized via hydrolysis.^L51738 In vitro, it appears minimally metabolized by CYP3A enzymes.^L51738

Rute Eliminasi

Following oral administration of a single radiolabeled dose of inavolisib, 49% of the administered dose was recovered in the urine (40% as unchanged parent drug) and 48% was recovered in the feces (11% as unchanged parent drug).^L51738

Interaksi Makanan

1 Data

1. Take with or without food. No clinically significant differences in inavolisib pharmacokinetics were observed following administration of inavolisib with a high-fat meal.

Interaksi Obat

0 Data

Tidak ada data.

Target Protein

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform PIK3CG

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform PIK3CA

Referensi & Sumber

Synthesis reference: Hanan EJ, Braun MG, Heald RA, MacLeod C, Chan C, Clausen S, Edgar KA, Eigenbrot C, Elliott R, Endres N, Friedman LS, Gogol E, Gu XH, Thibodeau RH, Jackson PS, Kiefer JR, Knight JD, Nannini M, Narukulla R, Pace A, Pang J, Purkey HE, Salphati L, Sampath D, Schmidt S, Sideris S, Song K, Sujatha-Bhaskar S, Ultsch M, Wallweber H, Xin J, Yeap S, Young A, Zhong Y, Staben ST: Discovery of GDC-0077 (Inavolisib), a Highly Selective Inhibitor and Degrader of Mutant PI3Kalpha. J Med Chem. 2022 Dec 22;65(24):16589-16621. doi: 10.1021/acs.jmedchem.2c01422. Epub 2022 Dec 1.

Artikel (PubMed)

PMID: 34544753
Song KW, Edgar KA, Hanan EJ, Hafner M, Oeh J, Merchant M, Sampath D, Nannini MA, Hong R, Phu L, Forrest WF, Stawiski E, Schmidt S, Endres N, Guan J, Wallin JJ, Cheong J, Plise EG, Lewis Phillips GD, Salphati L, Heffron TP, Olivero AG, Malek S, Staben ST, Kirkpatrick DS, Dey A, Friedman LS: RTK-Dependent Inducible Degradation of Mutant PI3Kalpha Drives GDC-0077 (Inavolisib) Efficacy. Cancer Discov. 2022 Jan;12(1):204-219. doi: 10.1158/2159-8290.CD-21-0072. Epub 2021 Sep 20.
PMID: 39437820
Sriravindrarajah A, Hurwitz J, Lim E, Greenfield JR: Hyperglycemia secondary to phosphatidylinositol-3 kinase (PI3K) inhibition. Endocrinol Diabetes Metab Case Rep. 2024 Oct 21;2024(4):24-0040. doi: 10.1530/EDM-24-0040. Print 2024 Oct 1.
PMID: 35022207
Vanhaesebroeck B, Burke JE, Madsen RR: Precision Targeting of Mutant PI3Kalpha in Cancer by Selective Degradation. Cancer Discov. 2022 Jan;12(1):20-22. doi: 10.1158/2159-8290.CD-21-1411.

Link

Contoh Produk & Brand

Produk: 2 • International brands: 0

Produk

Itovebi

Tablet, film coated • 9 mg/1 • Oral • US • Approved
Itovebi

Tablet, film coated • 3 mg/1 • Oral • US • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.