Peringatan Keamanan

Doses of PX-12 up to 226 mg/m2 were shown to be well tolerated and had minimal toxicity

PX-12

DB05448

small molecule investigational

Deskripsi

PX-12 (1-methylpropyl 2-imidazolyl disulfide) is a small-molecule inhibitor of Trx-1 (thioredoxin-1), stimulates apoptosis, down-regulates HIF-1? and vascular endothelial growth factor (VEGF) and inhibits tumor growth in animal models. Since high levels of Trx-1 have been associated with colorectal, gastric and lung cancers, PX-12 is indicated as a potential cancer treatment in combination with chemotherapy for patients with advanced metastatic cancer. Initial trials correlated doses of Px-12 with increased patient survival.

Struktur Molekul 2D

Berat 188.314

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) -

Volume Distribusi -

Klirens (Clearance) -

Absorpsi

the optimum PD dose was identified as 96 mg/m2 as a 3-hr infusion

Metabolisme

Data metabolisme tidak tersedia.

Rute Eliminasi

Data eliminasi belum tersedia.

Interaksi Obat

0 Data

Tidak ada data.

Target Protein

Thioredoxin TXN

Thioredoxin reductase 1, cytoplasmic TXNRD1

Referensi & Sumber

Artikel (PubMed)

PMID: 15701837
Jordan BF, Runquist M, Raghunand N, Gillies RJ, Tate WR, Powis G, Baker AF: The thioredoxin-1 inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) decreases vascular permeability in tumor xenografts monitored by dynamic contrast enhanced magnetic resonance imaging. Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):529-36.
PMID: 17805439
Bayes M, Rabasseda X, Prous JR: Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2007 Jun;29(5):359-73.
PMID: 17404093
Ramanathan RK, Kirkpatrick DL, Belani CP, Friedland D, Green SB, Chow HH, Cordova CA, Stratton SP, Sharlow ER, Baker A, Dragovich T: A Phase I pharmacokinetic and pharmacodynamic study of PX-12, a novel inhibitor of thioredoxin-1, in patients with advanced solid tumors. Clin Cancer Res. 2007 Apr 1;13(7):2109-14.
PMID: 17209529
Galmarini CM: Drug evaluation: the thioredoxin inhibitor PX-12 in the treatment of cancer. Curr Opin Investig Drugs. 2006 Dec;7(12):1108-15.
PMID: 17115210
Kiviharju K, Moilanen U, Leisola M, Eerikainen T: A chemostat study of Streptomyces peucetius var. caesius N47. Appl Microbiol Biotechnol. 2007 Jan;73(6):1267-74. Epub 2006 Nov 7.
PMID: 16459166
Baker AF, Dragovich T, Tate WR, Ramanathan RK, Roe D, Hsu CH, Kirkpatrick DL, Powis G: The antitumor thioredoxin-1 inhibitor PX-12 (1-methylpropyl 2-imidazolyl disulfide) decreases thioredoxin-1 and VEGF levels in cancer patient plasma. J Lab Clin Med. 2006 Feb;147(2):83-90.
PMID: 15148527
Bayes M, Rabasseda X, Prous JR: Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Apr;26(3):211-44.
PMID: 12847685
Bergink AP, van Meurs JB, Loughlin J, Arp PP, Fang Y, Hofman A, van Leeuwen JP, van Duijn CM, Uitterlinden AG, Pols HA: Estrogen receptor alpha gene haplotype is associated with radiographic osteoarthritis of the knee in elderly men and women. Arthritis Rheum. 2003 Jul;48(7):1913-22.

Menampilkan 8 dari 10 artikel.

Contoh Produk & Brand

Produk: 0 • International brands: 0

Belum ada data produk/brand untuk obat ini pada database. Jalankan import DrugBank untuk mengisi field produk/brand.

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.