CAS NO: | 146464-95-1 |
规格: | ≥98% |
包装 | 价格(元) |
10mg | 电议 |
25mg | 电议 |
50mg | 电议 |
100mg | 电议 |
250mg | 电议 |
500mg | 电议 |
Molecular Weight (MW) | 477.47 |
---|---|
Formula | C23H23N7O5 |
CAS No. | 146464-95-1(racemic); |
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 | |
Other info | Chemical Name: N -(4-{1-[(2,4-diaminopteridin-6-yl)methyl]but-3-yn-1-yl}benzoyl)-L-glutamic acid InChi Key: OGSBUKJUDHAQEA-WMCAAGNKSA-N InChi Code: InChI=1S/C23H23N7O5/c1-2-3-14(10-15-11-26-20-18(27-15)19(24)29-23(25)30-20)12-4-6-13(7-5-12)21(33)28-16(22(34)35)8-9-17(31)32/h1,4-7,11,14,16H,3,8-10H2,(H,28,33)(H,31,32)(H,34,35)(H4,24,25,26,29,30)/t14?,16-/m0/s1 SMILES Code: O=C(O)CC[C@@H](C(O)=O)NC(C1=CC=C(C(CC2=NC3=C(N)N=C(N)N=C3N=C2)CC#C)C=C1)=O |
Synonyms | PDX; Pralatrexate; 10-Propargyl-10-deazaaminopterin; trade name: Folotyn. |
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. Pralatrexate's 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 Cell Assay: Pralatrexate(Folotyn) is an antifolate, and structurally a folate analog. Its IC50 is < 300 nM in some cell lines. Based on preclinical studies, researchers believe that Pralatrexate selectively enters cells expressing reduced folate carrier type 1 (RFC-1), a protein that is overexpressed on certain cancer cells compared to normal cells. |
---|---|
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 | MV522 mice |
Formulation & Dosage | N/A |
References | Clin Cancer Res. 2010 Jul 15;16(14):3648-58; Cancer Chemother Pharmacol. 2009 Oct;64(5):993-9. |