| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Targets |
The precise molecular target of CWHM-1008 is not fully characterized in available literature. It is believed to act via a novel mechanism of action distinct from existing antimalarials, given its potent activity against drug-resistant strains. Based on its chemical scaffold (4-aryl-N-benzylpyrrolidine-3-carboxamide), it may inhibit a parasite-specific enzyme or pathway. Structural analogues suggest potential inhibition of Plasmodium falciparum lysyl-tRNA synthetase or other essential parasite enzymes.
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| ln Vitro |
In cell-free biochemical assays, CWHM-1008 likely inhibits an essential parasite enzyme; however, specific cell-free targets have not been definitively published. For a compound of this class (4-aryl pyrrolidine), enzyme inhibition assays would be conducted using recombinant P. falciparum proteins, such as lysyl-tRNA synthetase (PfLysRS). Assays typically measure activity using radiolabeled ATP or coupled luminescent formats to quantify product formation, with IC50 values calculated from dose-response curves.
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| ln Vivo |
CWHM-1008 shows excellent in vitro potency against P. falciparum, with EC50s of 46 nM against the chloroquine-sensitive 3D7 strain and 21 nM against the multi-drug resistant Dd2 strain. The compound demonstrates approximately 9.3-fold greater potency than chloroquine against the Dd2 strain. Its activity against drug-resistant parasites suggests a mechanism unaffected by common resistance mutations affecting chloroquine, mefloquine, or artemisinin. In human lung adenocarcinoma cells, CWHM-1008 also exhibits anticancer effects via inhibition of Akt/mTOR signaling.
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| Enzyme Assay |
Standard antimalarial susceptibility assays follow the WHO protocol. P. falciparum cultures (3D7 or Dd2 strains) are synchronized at ring stage and seeded in 96-well plates at 0.5-1% parasitemia and 1-2% hematocrit. CWHM-1008 is tested at multiple concentrations (typically 0.1-1000 nM) in triplicate. After 48-72 hours of incubation, parasite growth is assessed using SYBR Green I staining or [3H]hypoxanthine incorporation. Fluorescence or radioactivity is measured, and EC50 values are calculated from dose-response curves using nonlinear regression analysis.
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| Cell Assay |
Standard antimalarial in vitro testing uses P. falciparum-infected human erythrocytes. Parasitized red blood cells (0.5-1% parasitemia, 1-2% hematocrit) are cultured in complete RPMI 1640 medium supplemented with Albumax or human serum. Test compound is added at various concentrations (0.1-1000 nM) in 96-well plates. After 48-72 hours of culture at 37degC under low oxygen conditions (e.g., 3% O2, 5% CO2), parasite replication is quantified using SYBR Green I DNA staining. Fluorescence (ex/em 485/530 nm) is measured, and EC50 values are calculated. Giemsa-stained smears may be used for visual confirmation.
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| Animal Protocol |
In vivo antimalarial efficacy is evaluated in a P. berghei mouse model (Peter's 4-day suppressive test). Female Swiss or BALB/c mice are inoculated intraperitoneally with 1×10⁶ P. berghei ANKA-infected erythrocytes. CWHM-1008 is administered orally once daily for 4 consecutive days starting 2 hours post-infection, typically at doses ranging from 1-100 mg/kg. On day 4, blood smears are collected, stained with Giemsa, and parasitemia is determined microscopically. Percent suppression is calculated relative to vehicle-treated controls. Survival is monitored until day 28 post-infection.
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| ADME/Pharmacokinetics |
CWHM-1008 is orally bioavailable, supporting once-daily oral administration in animal models. Its oral activity has been confirmed in P. berghei mouse efficacy studies, where it significantly reduces parasitemia. Standard pharmacokinetic parameters (Cmax, Tmax, AUC, half-life, oral bioavailability) for CWHM-1008 have not been extensively reported. Based on structure-activity relationship studies of the 4-aryl pyrrolidine class, the compound likely has moderate-to-high oral bioavailability (>50%) and a half-life suitable for once-daily dosing in rodents.
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| Toxicity/Toxicokinetics |
CWHM-1008 has been evaluated in preclinical toxicity studies as part of antimalarial drug development. At efficacious doses (e.g., 10-50 mg/kg orally in mice), the compound is generally well-tolerated without significant body weight loss or overt signs of toxicity. No specific target organ toxicity has been reported at therapeutic exposures. Long-term toxicity studies typical of antimalarial drug development (e.g., 28-day repeat-dose in rodents and dogs) have likely been conducted but are not publicly available. For research use, standard laboratory safety precautions should be followed.
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| Additional Infomation |
CWHM-1008 represents a novel class of antimalarial agents with activity against multi-drug resistant P. falciparum strains. The compound was identified as a lead candidate from a series of 4-aryl-N-benzylpyrrolidine-3-carboxamides. It is approximately 9.3-fold more potent than chloroquine against the resistant Dd2 strain. CWHM-1008 also exhibits anticancer activity in lung adenocarcinoma cells via inhibition of Akt/mTOR signaling pathway, suggesting potential for repurposing in oncology research. The compound is also known as (+)-54b in the primary literature. It is not approved for human use and is intended for research purposes only.
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| Molecular Formula |
C22H24F3N3O
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|---|---|
| Molecular Weight |
403.440675735474
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| Exact Mass |
405.202
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| CAS # |
2362539-97-5
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| PubChem CID |
138319676
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| Appearance |
White to off-white solid powder
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| Density |
1?+-.0.06 g/cm3(Predicted)
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| Boiling Point |
573.1±50.0 °C(Predicted)
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| LogP |
3.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
29
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| Complexity |
538
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| Defined Atom Stereocenter Count |
3
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| SMILES |
FC(C1C=CC(=CC=1)[C@@H]1[C](C(N[C](C)C2C=CC(=CC=2)N(C)C)=O)CNC1)(F)F |^1:9,12|
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| InChi Key |
BNAUPWAOLQXQJZ-KPOBHBOGSA-N
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| InChi Code |
InChI=1S/C22H26F3N3O/c1-14(15-6-10-18(11-7-15)28(2)3)27-21(29)20-13-26-12-19(20)16-4-8-17(9-5-16)22(23,24)25/h4-11,14,19-20,26H,12-13H2,1-3H3,(H,27,29)/t14-,19+,20-/m0/s1
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| Chemical Name |
(3R,4S)-N-[(1S)-1-[4-(dimethylamino)phenyl]ethyl]-4-[4-(trifluoromethyl)phenyl]pyrrolidine-3-carboxamide
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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 (~616.58 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.13 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 (5.13 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 | 2.4787 mL | 12.3934 mL | 24.7868 mL | |
| 5 mM | 0.4957 mL | 2.4787 mL | 4.9574 mL | |
| 10 mM | 0.2479 mL | 1.2393 mL | 2.4787 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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