TTBK1-IN-2 (compound 29) is a potent inhibitor of Tau-Tubulin kinase (TTBK1) with IC50 of 0.24 and 4.22 µM, respectively. TTBK1-IN-2 showed good brain penetration in vivo and was able to reduce TDP-43 phosphorylation not only in cell culture but also in the spinal cord of transgenic TDP-43 mice.

Physicochemical Properties

Molecular Formula	C18H13CLN4O
Molecular Weight	336.78
Exact Mass	336.077
CAS #	2765453-51-6
PubChem CID	162679313
Appearance	Off-white to light yellow solid powder
LogP	4.7
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	24
Complexity	397
Defined Atom Stereocenter Count	0
InChi Key	RWRSKMSFZCQDMQ-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H13ClN4O/c19-12-1-5-14(6-2-12)24-15-7-3-13(4-8-15)23-18-16-9-10-20-17(16)21-11-22-18/h1-11H,(H2,20,21,22,23)
Chemical Name	N-[4-(4-chlorophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine
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 Note: This product requires protection from light (avoid light exposure) during transportation and storage.
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

References

[1]. Nozal V, et al. TDP-43 Modulation by Tau-Tubulin Kinase 1 Inhibitors: A New Avenue for Future Amyotrophic Lateral Sclerosis Therapy. J Med Chem. 2022;65(2):1585-1607.

Solubility Data

Solubility (In Vitro)

DMSO: 50 mg/mL (148.46 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.42 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 25.0 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: ≥ 2.5 mg/mL (7.42 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline 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	2.9693 mL	14.8465 mL	29.6930 mL
	5 mM	0.5939 mL	2.9693 mL	5.9386 mL
	10 mM	0.2969 mL	1.4846 mL	2.9693 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.