TCMDC-135051 TFA 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 | 585.61 Formula |
| Exact Mass | 471.252 |
| 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) |
| LogP | 3.5 |
| 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 |
| InChi Key | XKLPRHHLSQBUIC-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C29H33N3O3/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) |
| Chemical Name | 4-[2-[5-(diethylaminomethyl)-2-methoxyphenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl]-2-propan-2-ylbenzoic acid |
| 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.) |