WR99210

• CAT Number: I010084
• CAS Number: 47326-86-3
• Molecular Formula: C14H18Cl3N5O2
• Molecular Weight: 394.681
• Purity: ≥95%
• Target: dihydrofolate reductase inhibitor
• Solubility: Soluble in DMSO
• Storage: 0 - 4 °C for short term, or -20 °C for long term
• IUPAC Name: 6,6-dimethyl-1-[3-(2,4,5-trichlorophenoxy)propoxy]-1,3,5-triazine-2,4-diamine
• InChI: InChI=1S/C14H18Cl3N5O2/c1-14(2)21-12(18)20-13(19)22(14)24-5-3-4-23-11-7-9(16)8(15)6-10(11)17/h6-7H,3-5H2,1-2H3,(H4,18,19,20,21)
• InChIKey: MJZJYWCQPMNPRM-UHFFFAOYSA-N
• SMILES: CC1(N=C(N=C(N1OCCCOC2=CC(=C(C=C2Cl)Cl)Cl)N)N)C

WR99210 (Cat.No:I010084) is a dihydrofolate reductase inhibitor, which has promising in vitro activity against Mycobacterium avium complex (MAC). WR99210 has been shown to be effective against other mycobacteria. WR99210 is also a potent inhibitor of M. tuberculosis and Mycobacterium bovis BCG growth in vitro and that resistance to WR99210 occurred less frequently than resistance to either rifampin or isoniazid.

Reference

1:Transfection of Babesia bovis by Double Selection with WR99210 and Blasticidin-S and Its Application for Functional Analysis of Thioredoxin Peroxidase-1. Asada M, Yahata K, Hakimi H, Yokoyama N, Igarashi I, Kaneko O, Suarez CE, Kawazu S.PLoS One. 2015 May 11;10(5):e0125993. doi: 10.1371/journal.pone.0125993. eCollection 2015. PMID: 25962142 Free PMC Article2:Stable expression of green fluorescent protein and targeted disruption of thioredoxin peroxidase-1 gene in Babesia bovis with the WR99210/dhfr selection system. Asada M, Tanaka M, Goto Y, Yokoyama N, Inoue N, Kawazu S.Mol Biochem Parasitol. 2012 Feb;181(2):162-70. doi: 10.1016/j.molbiopara.2011.11.001. Epub 2011 Nov 15. PMID: 22108434 3:Conflicting requirements of Plasmodium falciparum dihydrofolate reductase mutations conferring resistance to pyrimethamine-WR99210 combination. Japrung D, Leartsakulpanich U, Chusacultanachai S, Yuthavong Y.Antimicrob Agents Chemother. 2007 Dec;51(12):4356-60. Epub 2007 Sep 17. PMID: 17875995 Free PMC Article4:An amino acid substitution in the Babesia bovis dihydrofolate reductase-thymidylate synthase gene is correlated to cross-resistance against pyrimethamine and WR99210. Gaffar FR, Wilschut K, Franssen FF, de Vries E.Mol Biochem Parasitol. 2004 Feb;133(2):209-19. PMID: 14698433 5:Novel Saccharomyces cerevisiae screen identifies WR99210 analogues that inhibit Mycobacterium tuberculosis dihydrofolate reductase. Gerum AB, Ulmer JE, Jacobus DP, Jensen NP, Sherman DR, Sibley CH.Antimicrob Agents Chemother. 2002 Nov;46(11):3362-9. PMID: 12384337 Free PMC Article6:Pyrimethamine and WR99210 exert opposing selection on dihydrofolate reductase from Plasmodium vivax. Hastings MD, Sibley CH.Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13137-41. Epub 2002 Aug 27. PMID: 12198181 Free PMC Article7:Novel alleles of the Plasmodium falciparum dhfr highly resistant to pyrimethamine and chlorcycloguanil, but not WR99210. Hankins EG, Warhurst DC, Sibley CH.Mol Biochem Parasitol. 2001 Sep 28;117(1):91-102. PMID: 11551635 8:Mutagenesis of dihydrofolate reductase from Plasmodium falciparum: analysis in Saccharomyces cerevisiae of triple mutant alleles resistant to pyrimethamine or WR99210. Ferlan JT, Mookherjee S, Okezie IN, Fulgence L, Sibley CH.Mol Biochem Parasitol. 2001 Mar;113(1):139-50. PMID: 11254962 9:Interaction of pyrimethamine, cycloguanil, WR99210 and their analogues with Plasmodium falciparum dihydrofolate reductase: structural basis of antifolate resistance. Rastelli G, Sirawaraporn W, Sompornpisut P, Vilaivan T, Kamchonwongpaisan S, Quarrell R, Lowe G, Thebtaranonth Y, Yuthavong Y.Bioorg Med Chem. 2000 May;8(5):1117-28. PMID: 10882022 10:The antimalarial triazine WR99210 and the prodrug PS-15: folate reversal of in vitro activity against Plasmodium falciparum and a non-antifolate mode of action of the prodrug. Kinyanjui SM, Mberu EK, Winstanley PA, Jacobus DP, Watkins WM.Am J Trop Med Hyg. 1999 Jun;60(6):943-7. PMID: 10403325