ABBV-4083, a Tylosin A analog with improvements in anti-Wolbachia and anti-filarial activity and oral pharmacokinetic properties, is a novel macrofilaricidal agent which acts by targeting the worm-symbiont Wolbachia bacterium. Chemical modification of TylA leads tos; ABBV-4083 has been selected for clinical evaluation.There is a significant need for improved treatments for onchocerciasis and lymphatic filariasis, diseases caused by filarial worm infection. In particular, an agent able to selectively kill adult worms (macrofilaricide) would be expected to substantially augment the benefits of mass drug administration (MDA) with current microfilaricides, and to provide a solution to treatment of onchocerciasis / loiasis co-infection, where MDA is restricted.
Physicochemical Properties
| Molecular Formula | C53H82FNO17 |
| Molecular Weight | 1024.21310186386 |
| Exact Mass | 1023.556 |
| CAS # | 1809266-03-2 |
| Related CAS # | 1809266-03-2; 1401-69-0 (Tylosin A) |
| PubChem CID | 92045060 |
| Appearance | Typically exists as solid at room temperature |
| LogP | 3.1 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 19 |
| Rotatable Bond Count | 16 |
| Heavy Atom Count | 72 |
| Complexity | 1770 |
| Defined Atom Stereocenter Count | 21 |
| SMILES | CC[C@@H]1[C@H](/C=C(/C=C/C(=O)[C@@H](C[C@@H]([C@@H]([C@H]([C@@H](CC(=O)O1)O)C)O[C@H]2[C@@H]([C@H]([C@@H]([C@H](O2)C)O[C@H]3C[C@@]([C@H]([C@@H](O3)C)OCC4=CC=C(C=C4)F)(C)O)N(C)C)O)CC=O)C)\C)CO[C@H]5[C@@H]([C@@H]([C@@H]([C@H](O5)C)O)OC)OC |
| InChi Key | FVQGMXUKQAXPIP-JLTQGABHSA-N |
| InChi Code | InChI=1S/C53H82FNO17/c1-13-40-36(27-66-52-49(64-12)48(63-11)44(60)31(5)68-52)22-28(2)14-19-38(57)29(3)23-35(20-21-56)46(30(4)39(58)24-41(59)70-40)72-51-45(61)43(55(9)10)47(32(6)69-51)71-42-25-53(8,62)50(33(7)67-42)65-26-34-15-17-37(54)18-16-34/h14-19,21-22,29-33,35-36,39-40,42-52,58,60-62H,13,20,23-27H2,1-12H3/b19-14+,28-22+/t29-,30+,31-,32-,33+,35+,36-,39-,40-,42+,43-,44-,45-,46-,47-,48-,49-,50+,51+,52-,53-/m1/s1 |
| Chemical Name | 2-[(4R,5S,6S,7R,9R,11E,13E,15R,16R)-6-[(2R,3R,4R,5S,6R)-4-(dimethylamino)-5-[(2S,4R,5S,6S)-5-[(4-fluorophenyl)methoxy]-4-hydroxy-4,6-dimethyloxan-2-yl]oxy-3-hydroxy-6-methyloxan-2-yl]oxy-16-ethyl-4-hydroxy-15-[[(2R,3R,4R,5R,6R)-5-hydroxy-3,4-dimethoxy-6-methyloxan-2-yl]oxymethyl]-5,9,13-trimethyl-2,10-dioxo-1-oxacyclohexadeca-11,13-dien-7-yl]acetaldehyde |
| Synonyms | ABBV-4083; ABBV 4083; ABBV4083 |
| 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
| ln Vivo | In recovered female adults, ABBV-4083 (150 mg/kg once daily for 14 days) decreased mouse Wolbachia levels by more than 99.9% (measured 16 weeks after therapy commencement, pti). Circulating microfilariae levels started to drop at 7 weeks after surgery and were totally eliminated from 12 weeks after surgery until the study's conclusion at 16 weeks [1]. |
| Animal Protocol |
Animal/Disease Models: Female balb/c (Bagg ALBino) mouse or female gerbils are infected with Lactobacillus sigmodium larvae at 6-8 weeks of age through the bite of Bacchus mites [1]. Doses: 150 mg/kg. Doses: Oral administration starting at 14 weeks post-infection (pti), one time/day for 14 days. Experimental Results: Wolbachia levels (measured 16 weeks after the start of treatment, pti) were diminished by more than 99.9% in recovered female adults. Levels of circulating microfilariae diminished starting approximately 7 weeks postinoculation and were completely cleared from 12 weeks postinoculation to 16 weeks postinoculation at the end of this study. |
| References |
[1]. Discovery of ABBV-4083, a novel analog of Tylosin A that has potent anti-Wolbachia and anti-filarial activity. PLoS Negl Trop Dis. 2019 Feb 28;13(2):e0007159. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9764 mL | 4.8818 mL | 9.7636 mL | |
| 5 mM | 0.1953 mL | 0.9764 mL | 1.9527 mL | |
| 10 mM | 0.0976 mL | 0.4882 mL | 0.9764 mL |