Pafuramidine

• CAT Number: I002416
• CAS Number: 186953-56-0
• Molecular Formula: C20H20N4O3
• Molecular Weight: 364.40
• Purity: ≥95%
• Synonyms: N/’-methoxy-4-[5-[4-[(Z)-N/’-methoxycarbamimidoyl]phenyl]furan-2-yl]benzenecarboximidamide
• Target: Antibiotic
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IC50: 4.5 nM (In vitro inhibitory activity against Trypanosoma brucei rhodesiense) [4]
• IUPAC Name: N'-methoxy-4-[5-[4-[(Z)-N'-methoxycarbamimidoyl]phenyl]furan-2-yl]benzenecarboximidamide
• InChI: InChI=1S/C20H20N4O3/c1-25-23-19(21)15-7-3-13(4-8-15)17-11-12-18(27-17)14-5-9-16(10-6-14)20(22)24-26-2/h3-12H,1-2H3,(H2,21,23)(H2,22,24)
• InChIKey: UKOQVLAXCBRRGH-UHFFFAOYSA-N
• SMILES: CO/N=C(\N)/C1=CC=C(C=C1)C2=CC=C(O2)C3=CC=C(C=C3)/C(=N/OC)/N

Pafuramidine（Cat No.:I002416）is a prodrug of furamidine (DB75) developed for the treatment of African sleeping sickness (Trypanosoma brucei) and Pneumocystis jirovecii pneumonia. Once metabolized, it acts as a DNA minor-groove binder, interfering with the replication and transcription of pathogenic DNA. Pafuramidine is particularly effective in early-stage sleeping sickness due to its oral bioavailability and ability to target the parasite without crossing the blood-brain barrier. Its favorable safety and efficacy profiles make it a promising candidate in combating neglected tropical diseases and advancing research on antiparasitic therapies.

Reference

1:Efficacy and Safety of Pafuramidine versus Pentamidine Maleate for Treatment of First Stage Sleeping Sickness in a Randomized, Comparator-Controlled, International Phase 3 Clinical Trial. Pohlig G, Bernhard SC, Blum J, Burri C, Mpanya A, Lubaki JP, Mpoto AM, Munungu BF, N/’tombe PM, Deo GK, Mutantu PN, Kuikumbi FM, Mintwo AF, Munungi AK, Dala A, Macharia S, Bilenge CM, Mesu VK, Franco JR, Dituvanga ND, Tidwell RR, Olson CA.PLoS Negl Trop Dis. 2016 Feb 16;10(2):e0004363. doi: 10.1371/journal.pntd.0004363. eCollection 2016 Feb. PMID: 26882015 Free PMC Article2:Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies. Burri C, Yeramian PD, Allen JL, Merolle A, Serge KK, Mpanya A, Lutumba P, Mesu VK, Bilenge CM, Lubaki JP, Mpoto AM, Thompson M, Munungu BF, Manuel F, Josenando T, Bernhard SC, Olson CA, Blum J, Tidwell RR, Pohlig G.PLoS Negl Trop Dis. 2016 Feb 16;10(2):e0004362. doi: 10.1371/journal.pntd.0004362. eCollection 2016 Feb. PMID: 26881924 Free PMC Article3:Pharmacology of DB844, an orally active aza analogue of pafuramidine, in a monkey model of second stage human African trypanosomiasis. Thuita JK, Wang MZ, Kagira JM, Denton CL, Paine MF, Mdachi RE, Murilla GA, Ching S, Boykin DW, Tidwell RR, Hall JE, Brun R.PLoS Negl Trop Dis. 2012;6(7):e1734. doi: 10.1371/journal.pntd.0001734. Epub 2012 Jul 24. PMID: 22848769 Free PMC Article4:Phase I/II evaluation of the prophylactic antimalarial activity of pafuramidine in healthy volunteers challenged with Plasmodium falciparum sporozoites. Nyunt MM, Hendrix CW, Bakshi RP, Kumar N, Shapiro TA.Am J Trop Med Hyg. 2009 Apr;80(4):528-35. PMID: 19346370 Free PMC Article5:Efficacy of the novel diamidine compound 2,5-Bis(4-amidinophenyl)- furan-bis-O-Methlylamidoxime (Pafuramidine, DB289) against Trypanosoma brucei rhodesiense infection in vervet monkeys after oral administration. Mdachi RE, Thuita JK, Kagira JM, Ngotho JM, Murilla GA, Ndung/’u JM, Tidwell RR, Hall JE, Brun R.Antimicrob Agents Chemother. 2009 Mar;53(3):953-7. doi: 10.1128/AAC.00831-08. Epub 2008 Dec 8. PMID: 19064893 Free PMC Article6:Pafuramidine for Pneumocystis jiroveci pneumonia in HIV-infected individuals. Chen D, Marsh R, Aberg JA.Expert Rev Anti Infect Ther. 2007 Dec;5(6):921-8. Review. PMID: 18039076 7:Human enteric microsomal CYP4F enzymes O-demethylate the antiparasitic prodrug pafuramidine. Wang MZ, Wu JQ, Bridges AS, Zeldin DC, Kornbluth S, Tidwell RR, Hall JE, Paine MF.Drug Metab Dispos. 2007 Nov;35(11):2067-75. Epub 2007 Aug 20. PMID: 17709372 Free PMC Article