product name Pralatrexate
Description: Pralatrexate is an antifolate, and structurally a folate analog. Its IC50 is < 300 nM in some cell lines. Pralatrexate exhibits high affinity for reduced folate carrier-1 (RFC-1) with antineoplastic and immunosuppressive activities. Pralatrexate selectively enters cells expressing RFC-1; it competes for the folate binding site of DHFR, blocking tetrahydrofolate synthesis, which may result in depletion of nucleotide precursors, inhibition of DNA/RNA/protein synthesis, and apoptotic tumor cell death.
References: Clin Cancer Res. 2010 Jul 15;16(14):3648-58; Cancer Chemother Pharmacol. 2009 Oct;64(5):993-9.
477.47
Formula
C23H23N7O5
CAS No.
146464-95-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 28 mg/mL (58.6 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19410547
| In Vitro |
In vitro activity: Pralatrexate and bortezomib exhibits concentration- and time-dependent cytotoxicity against a broad panel of T-lymphoma cell lines. Pralatrexate shows synergism when combined with bortezomib in all cell lines studied. Pralatrexate also induces potent apoptosis and caspase activation when combined with bortezomib across the panel. Pralatrexate significantly modulates the expression of p27, NOXA, HH3, and RFC-1 as assessed by Western blot assays. Pralatrexate is rationally designed for improved cellular transport via RFC-1, and to have greater intracellular drug retention through the enhanced formation of polyglutamylated conjugates. Pralatrexate is thought to exert its pharmacological effect primarily through inhibition of DHFR, having an IC50 in the picomolar range. Pralatrexate demonstrates superior intracellular transport via the reduced folate carrier, and increased accumulation within cells by enhanced polyglutamylation. Pralatrexate exhibits antitumor activity that is superior to the activity of other antifolates. Pralatrexates enhanced activity relative to methotrexate (MTX) is due to its much more rapid rate of transport and polyglutamation, the former less important when the carrier is saturated Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | Pralatrexate treatment results in treatment-related toxicity in MV522 mice models, as determined by significant weight loss in some animals prior to death; however, remaining mice regains all lost weight by Day 35. |
| Animal model | |
| Formulation & Dosage | |
| References | Clin Cancer Res. 2010 Jul 15;16(14):3648-58; Cancer Chemother Pharmacol. 2009 Oct;64(5):993-9. |
