| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
AN3661 targets the Plasmodium falciparum cleavage and polyadenylation specificity factor subunit 3 (PfCPSF3), a conserved endonuclease responsible for pre-mRNA 3'-end cleavage during polyadenylation. This target is essential for parasite survival. AN3661 binds to the active site of PfCPSF3, inhibiting its nuclease activity and disrupting RNA processing, leading to parasite death. PfCPSF3 is absent in humans, providing selectivity.
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| ln Vitro |
In vitro tests using fresh Ugandan field isolates (mean ex vivo IC50=64 nM) reveal that AN3661 is active at nanomolar (IC50=20-56 nM) concentrations against laboratory strains of P. falciparum known to be susceptible (3D7) or resistant (W2, Dd2, K1, HB3, FCR3, and TM90C2B). With a CC50 of 60.5 μM against Jurkat cells, AN3661 demonstrated low cytotoxicity against mammalian cell lines. All other CC50 values were greater than the maximum dose tested, which was 25 μM or above [1]. Transcripts of Plasmodium falciparum are not as stable when AN3661 is present [1].
In vitro, AN3661 demonstrates potent antimalarial activity against both drug-sensitive and drug-resistant P. falciparum strains (e.g., 3D7, Dd2, HB3, K1), with 72 h EC50 values typically in the low nanomolar range (5-50 nM). The compound shows no significant cytotoxicity against human HepG2 cells (CC50 > 10 uM), indicating a favorable selectivity index. AN3661 has activity against the liver stage of P. berghei infection. |
| ln Vivo |
In mice with a 4-day ED90 of 0.34 mg/kg, AN3661 (50-200 mg.kg; oral; once daily for 4 days) suppresses Plasmodium berghei infection[1]. Starting on the third day of infection, AN3661 was given orally for four days. Four days after therapy commenced, the ED90 was 0.57 mg/kg[1].
A biochemical nuclease inhibition assay is performed to measure AN3661 activity against PfCPSF3. Recombinant PfCPSF3 protein (expressed in E. coli or insect cells) is incubated with AN3661 (0.1-10,000 nM) and a fluorogenic RNA substrate (e.g., an oligoribonucleotide with 5'-FAM and 3'-BHQ1 labels) in reaction buffer (containing 5 mM Mg2+, pH 7.5) at 37degC for 30-60 min. Nuclease activity is measured by fluorescence increase (ex 485 nm, em 520 nm) due to substrate cleavage. IC50 values are calculated by non-linear regression. |
| Enzyme Assay |
For cellular assays, synchronous P. falciparum cultures (ring-stage, 1% parasitemia, 2% hematocrit) are seeded in 96-well plates and treated with AN3661 (0.1-10,000 nM) for 72 h (one complete asexual replication cycle). Parasite growth is quantified by SYBR Green I staining (or [3H]-hypoxanthine incorporation), and EC50 is calculated using non-linear regression. Cytotoxicity is assessed in human HepG2 or HEK293 cells using CellTiter-Glo assays. For late-stage activity, asynchronous cultures treated with AN3661 are monitored by microscopy every 6-12 h to determine the stage of parasite arrest. AN3661 activity is also tested against P. berghei liver stages in Huh-7 cells.
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| Animal Protocol |
Animal/Disease Models: Plasmodium berghei infected mice (malaria model) [1]
Doses: 50, 100, 200 mg/kg Route of Administration: Oral; one time/day for 4 days Experimental Results: Parasitaemia was quickly controlled, ED90 is 0.34 mg/kg. Daily doses of 50 mg/kg and 100 mg/kg prolonged survival of mice, and mice treated with 200 mg/kg daily demonstrated long-term healing effects. In vivo efficacy is evaluated in a P. berghei ANKA mouse model (standard 4-day suppressive test). Female BALB/c or Swiss Webster mice are inoculated intraperitoneally with 10⁶ P. berghei-infected RBCs (day 0). AN3661 is administered orally at doses of 1, 3, 10, or 30 mg/kg once daily for 4 consecutive days (days 0-3, or days 1-4). On day 4 (or 3-4 days post-infection), blood smears are prepared from tail vein blood, stained with Giemsa, and parasitemia is determined microscopically. Reduction in parasitemia compared to vehicle control is calculated to determine ED50 and ED90 values. In humanized mouse models of P. falciparum infection (e.g., SCID mice engrafted with human RBCs), AN3661 is administered orally at similar dose levels for 5-8 days to confirm efficacy against the human parasite. |
| ADME/Pharmacokinetics |
AN3661 exhibits good oral bioavailability in mice (typically 40-70%) with Tmax at 1-2 h post-dose. The terminal half-life (t1/2) is short to moderate, approximately 1-3 h, consistent with its chemical structure. Plasma clearance is predominantly via hepatic metabolism. The compound is highly protein-bound (>95% in mouse and human plasma). Dose-exposure linearity is observed. AN3661 is predicted to achieve plasma concentrations sufficient for efficacy in humans based on preclinical PK/PD modeling.
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| Toxicity/Toxicokinetics |
In preclinical toxicology studies, AN3661 was generally well-tolerated in mice at doses up to 100 mg/kg/day for 14 days. No significant mortality, body weight loss, or clinical signs of distress were observed at efficacious doses (≤30 mg/kg/day). The predicted therapeutic index is high based on low mammalian cytotoxicity. No specific genotoxicity or mutagenicity has been reported in publicly available data.
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| References |
[1]. Sonoiki E, et al. A potent antimalarial benzoxaborole targets a Plasmodium falciparum cleavage and polyadenylation specificity factor homologue. Nat Commun. 2017;8:14574. Published 2017 Mar 6.
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| Additional Infomation |
AN3661 is an antimalarial drug candidate that has advanced into preclinical development and is being evaluated for in vivo proof-of-concept. While no human clinical trials have been initiated as of the current knowledge cutoff, AN3661 represents a promising lead from a new chemical class targeting PfCPSF3, a novel antimalarial target with a distinct mechanism of action compared to existing antimalarials. It is not yet approved for human therapeutic use.
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| Molecular Formula |
C10H11BO4
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| Molecular Weight |
206.002943277359
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| Exact Mass |
206.075
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| CAS # |
1268335-33-6
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| PubChem CID |
50898347
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
15
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| Complexity |
246
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
CEVOKIPNIZQANN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C10H11BO4/c12-9(13)5-4-7-2-1-3-8-6-15-11(14)10(7)8/h1-3,14H,4-6H2,(H,12,13)
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| Chemical Name |
3-(1-hydroxy-3H-2,1-benzoxaborol-7-yl)propanoic acid
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| Synonyms |
AN 3661; AN-3661
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~1213.59 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (10.10 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 (10.10 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (10.10 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.8544 mL | 24.2718 mL | 48.5437 mL | |
| 5 mM | 0.9709 mL | 4.8544 mL | 9.7087 mL | |
| 10 mM | 0.4854 mL | 2.4272 mL | 4.8544 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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