I can't tell you why, but I can confirm that I've had the same issue with this product. The IC50 in our tests (Dd2 strain) is in the micromolar range, much higher than it should be.

I suggest you find an alternative source. We've been using WR from D. Jacobus of Jacobus Pharmaceuticals.

Thank you Priscilla. Do you know whether Jacobus Phasrmaceuticals still producing WR99210?

Sorry, I do not. You'd have to contact them.

We actually had that problem and my feeling is the drug doesn't dissolve completely in DMSO, it always looks very cloudy and you can see particles in the solution even if you dilute more. I don't know if another provider is the solution, you can try and let us know ;) 

I'm currently using pyrimethamine instead since it also targets the dhfr gene, haven't had any problems with it

Thank you Pilar. We actually were using the product from Jacobus Pharmaceutical but it seems they are not manufacturing the drug anymore and the one from Sigma doesnt work. I think they best way is shifting to pyrimethmine. 

We are having the same problem with sigma's WR99210. What concentration of pyrimethamine are you using Hassan?

Actually, we are using pyrimethamine for in vivo experiment in mice with 70 µg/ml in drinking water. For in vitro experiment, maybe Pilar give us some help.

I am using the Sigma WR99120. The solution is cloudy at first in DMSO, but if you heat it for a couple of minutes at 37 C it gets clear. (solution 10 mM, approx. 5mg WR99120/1.2 mL DMSO (anhydrous).

Thank you Alexandre. Have you measured IC50 of WR99210 from sigma for P. falciparum?

I have not measured the IC50, however 2.5 nM is enough to kill P. falciparum parasites (3D7).  The issue with WR99120 in mice is that the compound is not soluble in water.

 I am facing the same problem. Is there any solution or update so far?

Unfortunately no solution yet Asim. Still we are dependent on WR99210 from Jacobus Pharmaceuticals

The WR99210 from Sigma does not work on P. falciparum at the recommended concentration (2.5-5 nM), whereas the same compound from Jacobus Pharmaceutical worked for me at that concentration for almost 8 years. It unlikely that solubility is an issue.

Sigma needs to address the problem.

One can yse pyrimethamine for P. falciparum. It works great in human serum medium, but its IC50 is much higher in albumax medium because of hypoxanthine. Hence, one has to determine IC50 of PYR for P. falciparum in albumax-hypoxanthine medium before deciding a concentration for selection.

Thanks Puran for the inputs.

There is an update on this topic

Preprint Isomerization of antimalarial drug WR99210 explains its inac...

Thanks Asim Azhar Siddiqui

Finally, we know why sigma WR99210 does not work. I hope Sigma consider modifying their product.