Pralatrexate

• CAT Number: A001168
• CAS Number: 146464-95-1
• Molecular Formula: C23H23N7O5
• Molecular Weight: 477.47
• Purity: ≥95%
• Target: DHFR
• Solubility: >23.9mg/mL in DMSO
• Storage: 3 years -20C powder
• InChI: 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
• InChIKey: OGSBUKJUDHAQEA-WMCAAGNKSA-N
• SMILES: 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

Pralatrexate is a folate analogue inhibitor of dihydrofolate reductase (DHFR) exhibiting high affinity for reduced folate carrier-1 (RFC-1) with antineoplastic and immunosuppressive activities. Pralatrexate selectively enters cells expressing RFC-1; intracellularly, this agent is highly polyglutamylated and competes for the folate binding site of DHFR, blocking tetrahydrofolate synthesis, which may result in depletion of nucleotide precursors; inhibition of DNA, RNA and protein synthesis; and apoptotic tumor cell death.

Reference

1:Results from a Phase I/II Open-Label, Dose-Finding Study of Pralatrexate and Oral Bexarotene in Patients with Relapsed/Refractory Cutaneous T-cell Lymphoma. Duvic M, Kim YH, Zinzani PL, Horwitz SM.Clin Cancer Res. 2017 Feb 6. doi: 10.1158/1078-0432.CCR-16-2064. [Epub ahead of print] PMID: 28167509 2:Blastic plasmacytoid dendritic cell neoplasm with transient response to pralatrexate. Arranto C, Tzankov A, Halter J.Ann Hematol. 2017 Apr;96(4):681-682. doi: 10.1007/s00277-016-2907-4. Epub 2016 Dec 24. No abstract available. PMID: 28013360 3:Phase 1 study evaluating the safety and pharmacokinetics of pralatrexate in relapsed/refractory advanced solid tumors and lymphoma patients with mild, moderate, and severe renal impairment. Kelly KR, Gabrail N, Weitman S, Sarantopoulos J, Olszanski AJ, Edenfield W, Venitz J, Reddy G, Yang A, Hasal SJ, Lockhart AC.Cancer Chemother Pharmacol. 2016 Nov;78(5):929-939. Epub 2016 Sep 16. PMID: 27638045 4:Phase 1 and 2 study of carboplatin and pralatrexate in patients with recurrent, platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer. Del Carmen MG, Supko JG, Horick NK, Rauh-Hain JA, Clark RM, Campos SM, Krasner CN, Atkinson T, Birrer MJ.Cancer. 2016 Nov 15;122(21):3297-3306. doi: 10.1002/cncr.30196. Epub 2016 Jul 15. PMID: 27421044 5:Identification and characterization of forced degradation products of pralatrexate injection by LC-PDA and LC-MS. Sastry RV, Venkatesan CS, Sastry BS, Mahesh K.J Pharm Biomed Anal. 2016 Nov 30;131:400-409. doi: 10.1016/j.jpba.2016.08.023. Epub 2016 Aug 29. PMID: 27643862 6:Pralatrexate in Combination with Bortezomib for Relapsed or Refractory Peripheral T Cell Lymphoma in 5 Elderly Patients. Lee SS, Jung SH, Ahn JS, Kim YK, Cho MS, Jung SY, Lee JJ, Kim HJ, Yang DH.J Korean Med Sci. 2016 Jul;31(7):1160-3. doi: 10.3346/jkms.2016.31.7.1160. Epub 2016 May 12. PMID: 27366017 Free PMC Article7:A phase 1, open-label, dose-escalation study of pralatrexate in combination with bortezomib in patients with relapsed/refractory multiple myeloma. Dunn TJ, Dinner S, Price E, Coutré SE, Gotlib J, Hao Y, Berube C, Medeiros BC, Liedtke M.Br J Haematol. 2016 Apr;173(2):253-9. doi: 10.1111/bjh.13946. Epub 2016 Apr 4. PMID: 27040320 8:Pralatrexate Monitoring Using a Commercially Available Methotrexate Assay to Avoid Potential Drug Interactions. McPherson JP, Vrontikis A, Sedillo C, Halwani AS, Gilreath JA.Pharmacotherapy. 2016 Feb;36(2):e8-e11. doi: 10.1002/phar.1699. Epub 2016 Jan 26. PMID: 26809959 9:A phase II study of cyclophosphamide, etoposide, vincristine and prednisone (CEOP) Alternating with Pralatrexate (P) as front line therapy for patients with peripheral T-cell lymphoma (PTCL): final results from the T- cell consortium trial. Advani RH, Ansell SM, Lechowicz MJ, Beaven AW, Loberiza F, Carson KR, Evens AM, Foss F, Horwitz S, Pro B, Pinter-Brown LC, Smith SM, Shustov AR, Savage KJ, Vose JM.Br J Haematol. 2016 Feb;172(4):535-44. doi: 10.1111/bjh.13855. Epub 2015 Dec 2. PMID: 26627450 10:Methotrexate and Pralatrexate. Wood GS, Wu J.Dermatol Clin. 2015 Oct;33(4):747-55. doi: 10.1016/j.det.2015.05.009. Epub 2015 Aug 1. Review. PMID: 26433846 Free Article