AWZ1066S is a novel, potent and highly specific anti-Wolbachia drug candidate for a short-course treatment of filariasis, with an EC50 of 2.5 nM in cell assay. AWZ1066S shows superior efficacy to existing anti-Wolbachia therapies in validated preclinical models of infection and has DMPK characteristics that are compatible with a short therapeutic regimen of 7 days or less. This candidate molecule is well-positioned for onward development and has the potential to make a significant impact on communities affected by filariasis.
Physicochemical Properties
| Molecular Formula | C19H19F3N6O |
| Molecular Weight | 404.388973474503 |
| Exact Mass | 404.157 |
| Elemental Analysis | C, 56.43; H, 4.74; F, 14.09; N, 20.78; O, 3.96 |
| CAS # | 2239272-16-1 |
| Related CAS # | 2239272-16-1; |
| PubChem CID | 135240137 |
| Appearance | Solid powder |
| LogP | 3 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 10 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 29 |
| Complexity | 539 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | C[C@H]1COCCN1C2=NC3=C(C=CC=N3)C(=N2)NCC4=C(N=CC=C4)C(F)(F)F |
| InChi Key | IZFVCNUAPFSNCO-LBPRGKRZSA-N |
| InChi Code | InChI=1S/C19H19F3N6O/c1-12-11-29-9-8-28(12)18-26-16-14(5-3-7-24-16)17(27-18)25-10-13-4-2-6-23-15(13)19(20,21)22/h2-7,12H,8-11H2,1H3,(H,24,25,26,27)/t12-/m0/s1 |
| Chemical Name | (S)-2-(3-methylmorpholino)-N-((2-(trifluoromethyl)pyridin-3-yl)methyl)pyrido[2,3-d]pyrimidin-4-amine |
| Synonyms | AWZ1066S; AWZ-1066S; AWZ 1066S; AWZ106S; AWZ-1066; AWZ 1066; |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | anti-Wolbachia(EC50=121 nM) |
| ln Vitro | Anti-Wolbachia activity of AWZ1066S has an EC50 value of 121 nM.AWZ1066S does not exhibit time-dependent inhibition across the five major human CYP450 isoforms (CYP1A, CYP2C9, CYP2C19, CYP2D6, CYP3A), but it does have weak CYP2C9 inhibitory activity (IC50 value: 9.7 μM) and weak CYP3A4 induced activity (IC50 value: 37 uM)[1]. |
| ln Vivo | AWZ1066S (oral; 50, 100 mg/kg; bid; for 7 days) has high anti-Wolbachia efficacy.AWZ1066S (i.v or p.o; 5, 10, 85, 90 242 mg/kg) can oral delivery and has good aqueous solubility and metabolic stability[1]. |
| References |
[1]. AWZ1066S, a highly specific anti-Wolbachia drug candidate for a short-course treatment of filariasis. Proc Natl Acad Sci U S A. 2019 Jan 22;116(4):1414-1419. |
| Additional Infomation | Anti-Wolbachia Agent AWZ1066S is an orally bioavailable synthetic compond that is active against the bacterium Wolbachia and that can potentially be used to treat diseases caused by namatodes of the family Filariodidea, such as lymphatic filariasis and onchocerciasis. Upon oral administration, the anti-Wolbachia agent AWZ1066S specifically kills Wolbachia through an as of yet not fully identified mechanism of action (MoA). In filarial nematodes-infected humans, adult worms need Wolbachia in order to grow, reproduce, and survive. Targeting Wolbachia may indirectly kill the adult parasitic worms and prevent filariasis. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~125 mg/mL (~309.11 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.14 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.14 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (5.14 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4729 mL | 12.3643 mL | 24.7286 mL | |
| 5 mM | 0.4946 mL | 2.4729 mL | 4.9457 mL | |
| 10 mM | 0.2473 mL | 1.2364 mL | 2.4729 mL |