Pralatrexate

Pralatrexate is a dihydrofolate reductase (DHFR) inhibitor (Ki = 13.4 pM) and antifolate. It inhibits growth of CCRF-CEM acute lymphocytic leukemia cells (IC50 = 0.04 µM), MDA-468, SK-BR-3, and ZR-75-1 breast cancer cells (IC50s = 0.11, 0.28, and 0.26 µM, respectively), and SK-LC8 and SK-LC16 non-small cell lung cancer cells (NSCLC, IC50s = 0.42 and 0.11 µM, respectively). In vivo, pralatrexate increases median survival from 21 to 40 days when administered in 4 doses of 15 mg/kg over 11 days in an H9 T cell lymphoma mouse xenograft model. Pralatrexate is transported into cells via the reduced folate carrier (RFC) and undergoes polyglutamation by folylpolyglutamate synthetase (FPGS) to a greater extent than methotrexate (Cay-13960) or pemetrexed (Cay-14269). Formulations containing pralatrexate have been used in the treatment of relapsed or refractory peripheral T cell lymphoma.Formal Name: N-[4-[1-[(2,4-diamino-6-pteridinyl)methyl]-3-butyn-1-yl]benzoyl]-L-glutamic acid. CAS Number: 146464-95-1. Synonyms: NSC 754230, PDX, 10-Propargyl-10-deazaaminopterin. Molecular Formula: C23H23N7O5. Formula Weight: 477.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 14 mg/ml, DMSO: 3 mg/ml, PBS (pH 7.2): 1 mg/ml. lambdamax: 241, 340 nm. SMILES: NC1=NC(N)=NC2=C1N=C(CC(CC#C)C3=CC=C(C(N[C@H](C(O)=O)CCC(O)=O)=O)C=C3)C=N2. 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. InChi Key: OGSBUKJUDHAQEA-WMCAAGNKSA-N.