1. Neuronal Signaling
  2. Tau Protein
  3. TTBK1/2-IN-3

TTBK1/2-IN-3 (Compound 10) is a potent inhibitor of tau tubulin kinase 1 (TTBK1) and TTBK2, with IC50 values of 579 nM and 258 nM, respectively. TTBK1/2-IN-3 inhibits the phosphorylation of TDP-43. TTBK1/2-IN-3 reduces the expression of primary cilia on the surface of iPSCs.

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TTBK1/2-IN-3

TTBK1/2-IN-3 Chemical Structure

CAS No. : 2857982-34-2

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Description

TTBK1/2-IN-3 (Compound 10) is a potent inhibitor of tau tubulin kinase 1 (TTBK1) and TTBK2, with IC50 values of 579 nM and 258 nM, respectively. TTBK1/2-IN-3 inhibits the phosphorylation of TDP-43. TTBK1/2-IN-3 reduces the expression of primary cilia on the surface of iPSCs[1].

In Vitro

TTBK1/2-IN-3 is a dual inhibitor of the purified kinase domains of TTBK1 and TTBK2, with stronger inhibitory activity against TTBK2 than against TTBK1 (IC50 = 258 nM for TTBK2, IC50 = 579 nM for TTBK1)[1].
TTBK1/2-IN-3 binds to human TTBK1 and TTBK2 in live, intact HEK293 cells, with greater potency against TTBK2 than TTBK1 (IC50 = 4.8 μM for TTBK2, IC50 = 9.1 μM for TTBK1), and exhibits stronger activity in permeabilized cells[1].
TTBK1/2-IN-3 (5 μM; 48 h) reduces phosphorylated and total TDP-43 protein levels in SH-SY5Y neuroblastoma cells[1].
TTBK1/2-IN-3 (0.1-1 μM; 24-72 h) potently inhibits primary cilia formation in human induced pluripotent stem cells (iPSCs) in a time- and dose-dependent manner[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis[1]

Cell Line: Human SH-SY5Y neuroblastoma cells
Concentration: 5 μM; 0.1, 0.5, 1 μM
Incubation Time: 48 h
Result: Decreased phospho-TDP-43 expression by ~45% at 5 μM after 48 h compared to untreated controls.
Decreased total TDP-43 expression by ~60% at 5 μM after 48 h compared to untreated controls.
Showed no significant change in total TDP-43 at lower concentrations (0.1, 0.5, 1 μM) after 48 hours.
Molecular Weight

346.43

Formula

C21H22N4O

CAS No.
SMILES

CC(CC)(O)C#CC1=CC2=C(NC3=C2C4=C(C=NC(N)=N4)CCC3)C=C1

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TTBK1/2-IN-3
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