Pralatrexate

Research use only, not for human use.

An antifolate that fuctions as a dihydrofolate reductase inhibitor for treatment of several malignancies.

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.

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.

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.

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

Cell Cycle/DNA Damage

Antifolate

DHFR

Cancer

Chemotherapeutic

146464-95-1

477.4726

C23H23N7O5

>98% (HPLC)

10 mM in DMSO

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|

L-Glutamic acid, N-[4-[1-[(2,4-diamino-6-pteridinyl)methyl]-3-butyn-1-yl]benzoyl]-

(-20℃)

With Ice Pack

≥ 2 years