| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
PfCLK3 (Plasmodium falciparum CLK3 kinase).
|
|---|---|
| ln Vitro |
In tests measuring liver invasion and development, TCMDC-135051 shown strong efficacy against Plasmodium berghei sporozoites, with a pEC50 value of 6.17 (EC50=0.40 μM) [1]. TCMDC-135051 exhibits near-equivalent inhibition of these two orthologs, with pIC50 values of 7.47 (IC50=0.033 μM) and 7.86 (IC50=0.013 μM), respectively, according to kinase tests utilizing recombinant PvCLK3 (P. vivax) and PbCLK3 (P. berghei) [1].
In vitro enzymatic assays demonstrate that TCMDC-135051 potently inhibits PfCLK3 kinase activity with high selectivity over human kinases. The compound shows significant antiparasiticidal activity against Plasmodium falciparum with an EC50 value of 320 nM. It effectively disrupts parasite transcription and prevents the trophozoite-to-schizont transition in the parasite life cycle. The compound exhibits low off-target toxicity in vitro, indicating a favorable selectivity profile for the parasite target over host cell proteins. |
| ln Vivo |
In vivo studies have demonstrated that TCMDC-135051 effectively reduces parasite transmission to mosquito vectors. The compound's ability to block the transition from trophozoite to schizont stages in the malaria parasite life cycle translates to reduced infectivity in animal models. While detailed pharmacokinetic and efficacy data in mammalian infection models are limited, the compound's potent antiplasmodial activity and transmission-blocking properties support its potential for further in vivo evaluation in malaria research.
|
| Enzyme Assay |
The inhibitory activity of TCMDC-135051 against PfCLK3 is typically assessed using kinase enzymatic assays. Recombinant PfCLK3 protein is incubated with a peptide substrate and ATP in the presence of varying concentrations of the test compound. The phosphorylation level of the substrate is measured using either radioactive ATP incorporation or fluorescence-based detection methods. IC50 values are calculated from dose-response curves to quantify the compound's potency against the target kinase. Selectivity against a panel of human kinases is assessed using similar biochemical assay formats.
|
| Cell Assay |
Antiparasitic activity is evaluated using in vitro cultures of Plasmodium falciparum (e.g., 3D7 strain). Parasite cultures are maintained in human erythrocytes under standard conditions. Serial dilutions of TCMDC-135051 are added to the cultures, and parasite growth is monitored after 48-72 hours of incubation using methods such as [3H]-hypoxanthine incorporation, SYBR Green I fluorescence, or microscopy-based counting. EC50 values are determined by plotting percentage inhibition against compound concentration. Cytotoxicity against mammalian cell lines is also assessed to evaluate selectivity.
|
| Animal Protocol |
In vivo efficacy of TCMDC-135051 is evaluated in mouse models of malaria infection, typically using Plasmodium berghei or Plasmodium yoelii. Mice are infected with parasitized erythrocytes and then treated with the compound via oral or intraperitoneal administration. Parasitemia is monitored by blood smear microscopy over several days post-treatment. Transmission-blocking activity is assessed by feeding mosquitoes on treated, infected mice and measuring oocyst formation in mosquito midguts.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of TCMDC-135051 have been characterized in preclinical species. The compound demonstrates oral bioavailability and brain penetration, supporting its potential for systemic and central nervous system applications. Key PK parameters include half-life, clearance, volume of distribution, and maximum concentration (Cmax) following administration. The compound's favorable drug-like properties, including moderate molecular weight (471.59) and appropriate lipophilicity, contribute to its pharmacokinetic profile, though detailed PK parameters are typically reported in the primary literature and product documentation.
|
| Toxicity/Toxicokinetics |
Toxicological evaluation of TCMDC-135051 indicates minimal off-target toxicity, suggesting a favorable safety profile for a research compound. In vitro cytotoxicity assays against mammalian cell lines show low toxicity at concentrations that are effective against Plasmodium falciparum. The compound's selectivity for the parasite kinase PfCLK3 over human kinases contributes to its reduced potential for off-target effects. Standard toxicology studies, including assessment of effects on cell viability, proliferation, and general cellular health, are typically conducted to establish the compound's safety window for research applications.
|
| References |
[1]. Alam MM, et al. Validation of the protein kinase PfCLK3 as a multistage cross-species malarial drug target. Science. 2019 Aug 30;365(6456). pii: eaau1682.
|
| Additional Infomation |
TCMDC-135051 is a research tool compound primarily used for studying malaria parasite biology, specifically the role of PfCLK3 in parasite transcription, development, and transmission. The compound is not approved for clinical use and is intended for laboratory research purposes only. Its mechanism of action involves inhibition of PfCLK3-mediated phosphorylation, which disrupts RNA processing and transcriptional regulation in Plasmodium falciparum. This compound is valuable for validating PfCLK3 as a potential drug target for malaria and for investigating the biology of parasite transmission.
|
| Molecular Formula |
C29H33N3O3
|
|---|---|
| Molecular Weight |
471.59062743187
|
| CAS # |
2413716-15-9
|
| Related CAS # |
TCMDC-135051 hydrochloride;2705545-47-5;TCMDC-135051 TFA;2571578-55-5
|
| PubChem CID |
139035060
|
| Appearance |
White to off-white solid powder
|
| Density |
1.173±0.06 g/cm3(Predicted)
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
35
|
| Complexity |
684
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O(C)C1C=CC(=CC=1C1=CC2C(=NC=CC=2C2=CC=C(C(=O)O)C(=C2)C(C)C)N1)CN(CC)CC
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~530.12 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (13.25 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 62.5 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1205 mL | 10.6024 mL | 21.2049 mL | |
| 5 mM | 0.4241 mL | 2.1205 mL | 4.2410 mL | |
| 10 mM | 0.2120 mL | 1.0602 mL | 2.1205 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
