WJM664 is a PfATP4 inhibitor. WJM664 exhibited potent asexual stage activity and high metabolic stability. Resistant selection and whole-genome sequencing revealed mutations in PfATP4, which was validated as the target by showing that analogs exhibited reduced potency against parasites with resistance conferring mutations in PfATP4, a metabolomic signature similar to that of the PfATP4 inhibitor KAE609, and inhibition of Na+-dependent ATPase activity consistent with on-target inhibition of PfATP4. WJM664 inhibited gamete development and blocked parasite transmission to mosquitoes but exhibited low efficacy in aPlasmodium berghei mouse model, which was attributed to ATP4 species differentiation and its moderate systemic exposure.
MedKoo Cat#: 128789
Name: WJM664
CAS#: N/A
Chemical Formula: C23H22ClFN4O4
Exact Mass: 472.1314
Molecular Weight: 472.90
Elemental Analysis: C, 58.42; H, 4.69; Cl, 7.50; F, 4.02; N, 11.85; O, 13.53
The following data is based on the product molecular weight 472.90 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
