AWZ1066S | CAS#2239272-16-1 | anti-Wolbachia

MedKoo Cat#: 555646 | Name: AWZ1066S

Description:

WARNING: This product is for research use only, not for human or veterinary use.

AWZ1066S is a highly specific anti-Wolbachia drug candidate for a short-course treatment of filariasis. 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.

Chemical Structure

AWZ1066S

CAS#2239272-16-1

Theoretical Analysis

MedKoo Cat#: 555646

Name: AWZ1066S

CAS#: 2239272-16-1

Chemical Formula: C19H19F3N6O

Exact Mass: 404.1572

Molecular Weight: 404.40

Elemental Analysis: C, 56.43; H, 4.74; F, 14.09; N, 20.78; O, 3.96

Price and Availability

Size	Price	Availability
25mg	USD 550.00	2 Weeks
50mg	USD 950.00	2 Weeks
100mg	USD 1,650.00	2 Weeks
200mg	USD 2,650.00	2 Weeks
1g	USD 5,850.00	2 Weeks
2g	USD 8,450.00	2 Weeks

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Related CAS #

2239272-16-1

Synonym

AWZ1066S; AWZ-1066S; AWZ 1066S; AWZ106S; AWZ-1066; AWZ 1066;

IUPAC/Chemical Name

(S)-2-(3-methylmorpholino)-N-((2-(trifluoromethyl)pyridin-3-yl)methyl)pyrido[2,3-d]pyrimidin-4-amine

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

SMILES Code

FC(C1=NC=CC=C1CNC2=C(C=CC=N3)C3=NC(N4[C@@H](C)COCC4)=N2)(F)F

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

AWZ1066S is an anti-Wolbachia drug candidate for a short-course treatment of filariasis, with an EC50 of 2.5 nM in cell assay.

In vitro activity:

AWZ1066 (racemic mixture) was active against Wolbachia in a cell-based assay with an EC50 of 2.6 ± 0.5 nM (Fig. 1B). In an orthogonal secondary in vitro assay utilizing microfilariae (mf) of the human parasite B. malayi, AWZ1066 reduced Wolbachia within the mf with an EC50 of 150 nM while having no effect on the viability and motility of the mf at up to the top testing concentration of 5 µM. Reference: Proc Natl Acad Sci U S A. 2019 Jan 22; 116(4): 1414–1419. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347715/

In vivo activity:

After 7 d of twice-daily treatment of AWZ1066S at either 100 or 50 mg/kg orally, Wolbachia load was reduced by >99% compared with control untreated animals, 18 wk post treatment (Kruskal–Wallis statistic 43.5, P < 0.0001; Fig. 2B). After AWZ1066S treatment, the peripheral blood microfilaremia began to decline from 6 wk post treatment. A state of amicrofilaremia (absence of mf in the blood) was evident from 14 wk post treatment in the 7-d AWZ1066S treatment groups, a state that was sustained until the end of the experiment at 18 wk post treatment. Thus, treatment with AWZ1066S for 7 d leads to sterilization and gradual depletion of mf with the assumption, based on extensive clinical trial data with doxycycline, that this will result in a “slow” killing of adult worms alongside an improved safety profile. Reference: Proc Natl Acad Sci U S A. 2019 Jan 22; 116(4): 1414–1419. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347715/

	Solvent	mg/mL	mM
Solubility
	DMSO	125.0	309.10

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 404.40 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

Formulation protocol:

1. Hong WD, Benayoud F, Nixon GL, Ford L, Johnston KL, Clare RH, Cassidy A, Cook DAN, Siu A, Shiotani M, Webborn PJH, Kavanagh S, Aljayyoussi G, Murphy E, Steven A, Archer J, Struever D, Frohberger SJ, Ehrens A, Hübner MP, Hoerauf A, Roberts AP, Hubbard ATM, Tate EW, Serwa RA, Leung SC, Qie L, Berry NG, Gusovsky F, Hemingway J, Turner JD, Taylor MJ, Ward SA, O'Neill PM. 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. doi: 10.1073/pnas.1816585116. Epub 2019 Jan 7. PMID: 30617067; PMCID: PMC6347715.

In vitro protocol:

In vivo protocol:

1: Hegde S, Marriott AE, Pionnier N, Steven A, Bulman C, Gunderson E, Vogel I, Koschel M, Ehrens A, Lustigman S, Voronin D, Tricoche N, Hoerauf A, Hübner MP, Sakanari J, Aljayyoussi G, Gusovsky F, Dagley J, Hong DW, O'Neill P, Ward SA, Taylor MJ, Turner JD. Combinations of the azaquinazoline anti-Wolbachia agent, AWZ1066S, with benzimidazole anthelmintics synergise to mediate sub- seven-day sterilising and curative efficacies in experimental models of filariasis. Front Microbiol. 2024 Feb 1;15:1346068. doi: 10.3389/fmicb.2024.1346068. PMID: 38362501; PMCID: PMC10867176. 2: Marriott AE, Dagley JL, Hegde S, Steven A, Fricks C, DiCosty U, Mansour A, Campbell EJ, Wilson CM, Gusovsky F, Ward SA, Hong WD, O'Neill P, Moorhead A, McCall S, McCall JW, Taylor MJ, Turner JD. Dirofilariasis mouse models for heartworm preclinical research. Front Microbiol. 2023 Jun 22;14:1208301. doi: 10.3389/fmicb.2023.1208301. PMID: 37426014; PMCID: PMC10324412. 3: Johnston KL, Hong WD, Turner JD, O'Neill PM, Ward SA, Taylor MJ. Anti- Wolbachia drugs for filariasis. Trends Parasitol. 2021 Dec;37(12):1068-1081. doi: 10.1016/j.pt.2021.06.004. Epub 2021 Jul 3. PMID: 34229954. 4: Hong WD, Benayoud F, Nixon GL, Ford L, Johnston KL, Clare RH, Cassidy A, Cook DAN, Siu A, Shiotani M, Webborn PJH, Kavanagh S, Aljayyoussi G, Murphy E, Steven A, Archer J, Struever D, Frohberger SJ, Ehrens A, Hübner MP, Hoerauf A, Roberts AP, Hubbard ATM, Tate EW, Serwa RA, Leung SC, Qie L, Berry NG, Gusovsky F, Hemingway J, Turner JD, Taylor MJ, Ward SA, O'Neill PM. 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. doi: 10.1073/pnas.1816585116. Epub 2019 Jan 7. PMID: 30617067; PMCID: PMC6347715.