TCMDC-135051 is a potent and highly selective protein kinase PfCLK3 inhibitor with low off-target toxicity. TCMDC-135051 TFA prevents trophozoite-to-schizont transition, disrupts transcription and reduces transmission to the mosquito vector. TCMDC-135051 TFA has antiparasiticidal activity (EC50=320 nM).

Physicochemical Properties

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)

Biological Activity

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].

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.

Solubility Data

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.