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| 5mg |
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| Targets |
TCMDC-135051 targets the protein kinase PfCLK3, an essential kinase in Plasmodium falciparum involved in transcriptional regulation and parasite development. Inhibition of PfCLK3 disrupts transcriptional processes and prevents the transition from trophozoite to schizont stages, thereby blocking parasite replication and transmission. The compound has an EC50 of 320 nM against Plasmodium falciparum.
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| ln Vitro |
In a liver invasion and development assay, TCMDC-135051 hydrochloride demonstrates strong action against P. berghei sporozoites, with a pEC50 value of 6.17 (EC50=0.40 μM). TCMDC-135051 hydrochloride exhibits near-equipotent inhibition at these two orthologs, according to kinase tests employing recombinant PvCLK3 (P. vivax) and PbCLK3 (P. berghei), with pIC50 values of 7.47 (IC50=0.033 μM) and 7.86 (IC50=0.013 μM), respectively[1].
In vitro, TCMDC-135051 HCl is a potent and selective inhibitor of PfCLK3 with low off-target toxicity. It has anti-parasitic activity against Plasmodium falciparum with an EC50 of 320 nM. The compound effectively hinders the transition of the parasite from trophozoite to schizont stages and disrupts transcriptional processes. |
| ln Vivo |
In vivo activity data for TCMDC-135051 are not extensively documented in publicly available literature. The compound is being studied as a promising lead compound for drug discovery against malaria. Its ability to reduce transmission to mosquito vectors suggests potential for blocking malaria transmission in vivo. Further studies are needed to fully characterize its in vivo efficacy.
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| Enzyme Assay |
The in vitro kinase inhibition assay for TCMDC-135051 involves measuring its inhibitory effect on PfCLK3 kinase activity. Recombinant PfCLK3 enzyme is incubated with varying concentrations of TCMDC-135051, ATP, and a peptide substrate. The extent of phosphorylation is measured using radiometric or fluorescence-based detection methods. The compound is a potent and selective inhibitor of PfCLK3 with low off-target toxicity.
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| Cell Assay |
In vitro cellular assays for TCMDC-135051 involve treating cultured Plasmodium falciparum parasites with varying concentrations of the compound. Parasite growth and development are assessed by microscopy to monitor the transition from trophozoite to schizont stages. Parasite viability is measured using SYBR Green or similar assays. The EC50 for anti-parasitic activity is determined from dose-response curves, with TCMDC-135051 showing an EC50 of 320 nM.
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| Animal Protocol |
In vivo animal experiments for TCMDC-135051 would typically use mouse models of malaria infection. Animals are infected with Plasmodium falciparum or Plasmodium berghei and treated with TCMDC-135051 via appropriate routes. Parasitemia is monitored by blood smears. Transmission to mosquito vectors is assessed by feeding mosquitoes on infected animals. The compound reduces transmission to mosquito vectors. Specific protocols are not extensively documented in public literature.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of TCMDC-135051 have not been extensively characterized in publicly available literature. The hydrochloride salt form enhances solubility and stability for laboratory use. As a small molecule kinase inhibitor, it is expected to have reasonable oral bioavailability. Specific PK parameters including half-life, Cmax, and metabolic pathways would be available from preclinical studies.
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| Toxicity/Toxicokinetics |
Toxicological data for TCMDC-135051 are limited in publicly available sources. The compound is described as having low off-target toxicity. However, systematic toxicology studies including acute, repeated-dose, genotoxicity, and reproductive toxicity have not been well documented. Standard safety pharmacology studies would be required for therapeutic development.
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| 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.
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| Additional Infomation |
TCMDC-135051 hydrochloride (CAS#: 2705545-47-5) is a potent and selective inhibitor of the Plasmodium falciparum protein kinase PfCLK3. It has anti-parasitic activity with an EC50 of 320 nM, prevents trophozoite to schizont transition, disrupts transcription, and reduces transmission to mosquito vectors. TCMDC-135051 is not approved for clinical use and remains a research compound for malaria drug discovery.
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| Exact Mass |
507.229
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| CAS # |
2705545-47-5
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| Related CAS # |
TCMDC-135051;2413716-15-9;TCMDC-135051 TFA;2571578-55-5
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| PubChem CID |
146673038
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
36
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| Complexity |
684
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCN(CC)CC1=CC(=C(C=C1)OC)C2=CC3=C(C=CN=C3N2)C4=CC(=C(C=C4)C(=O)O)C(C)C.Cl
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| InChi Key |
PVXALYWEXUVTGW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H33N3O3.ClH/c1-6-32(7-2)17-19-8-11-27(35-5)25(14-19)26-16-24-21(12-13-30-28(24)31-26)20-9-10-22(29(33)34)23(15-20)18(3)4;/h8-16,18H,6-7,17H2,1-5H3,(H,30,31)(H,33,34);1H
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| Chemical Name |
4-[2-[5-(diethylaminomethyl)-2-methoxyphenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl]-2-propan-2-ylbenzoic acid;hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : 83.33 mg/mL (164.02 mM)
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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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