Pralatrexate

SKU: orb1226226

Description

An antifolate that fuctions as a dihydrofolate reductase inhibitor for treatment of several malignancies.Chemotherapeutic Agents Approved(In Vitro):Pralatrexate (100 pM-200 μM; 48-72 hours; T-lymphoma cell lines) treatment exhibits concentration- and time-dependent cytotoxicity against a broad panel of T-lymphoma cell lines. The IC50 values at 48 and 72 hours, respectively, are as follows: H9 cells, 1.1 nM and 2.5 nM; P12 cells, 1.7 nM and 2.4 nM; CEM cells, 3.2 nM and 4.2 nM; PF-382 cells, 5.5 nM and 2.7 nM; KOPT-K1 cells, 1 nM and 1.7 nM; DND-41 cells, 97.4 nM and 1.2 nM; and HPB-ALL cells, 247.8 nM and 0.77 nM. HH cells are relatively resistant after 48 hours of exposure, with the IC50 at 72 hours being 2.8 nM.Pralatrexate (2-5.5 nM; 48-72 hours; H9, HH, P12 and PF382 cells) treatment induces potent apoptosis, and caspase-8 and caspase-9 activation.Pralatrexate (3 nM; 16-48 hours; H9 and P12 cells) treatment clearly increases p27 levels and increases the accumulation of educed folate carrier type 1 (RFC-1) in cells.(In Vivo):The addition of Pralatrexate (15 mg/kg; intraperitoneal injection; on days 1, 4, 8, and 11; SCID-beige mice) to Bortezomib (0.5 mg/kg) enhanced efficacy compared with either drug alone.

Key Properties

• CAS Number: 146464-95-1
• MW: 477.4726
• Purity: >98% (HPLC)
• Formula: C₂₃H₂₃N₇O₅
• SMILES: NC1=NC(N)=C2N=C(CC(CC#C)C3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=NC2=N1 |r,c:15,17,32,35,t:1,4,6,13|
• Target: Antifolate
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  Animal model: SCID-beige mice (5-7-week-old) injected with HH cells. Dosage: 15 mg/kg. Administration: Intraperitoneal injection; on days 1, 4, 8, and 11. Result: Showed superior efficacy in T-cell malignancies.
• In Vitro:
  Cell Cytotoxicity Assay Cell line: T-lymphoma cell lines. Concentration: 100 pM-200 μM. Incubation time: 48 hours, 72 hours. Result: Exhibited concentration- and time-dependent cytotoxicity against a broad panel of T-lymphoma cell lines. Apoptosis Analysis Cell line: H9, HH, P12 and PF382 cells. Concentration: 2 nM, 3 nM, 4 nM, 5.5 nM Incubation time: 48 hours, 72 hours. Result: Induced potent apoptosis and caspase activation. Western blot analysis. Cell line: H9 and P12 cells. Concentration: 3 nM. Incubation time: 16 hours, 24 hours, 48 hours. Result: Clearly increased p27 levels and increased the accumulation of RFC-1 in cells.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

NSC 754230 | PDX | 10-Propargyl-10-deazaaminopterin

Quick Database Links

Gene Symbol

Antifolate