TPT-260  (Synonyms: TPU260)

TPT-260 (TPU260), a thiophene thiourea derivative, is a retromer complex stabilizer against thermal denaturation (K_d = ~5 µM). TPT-260 increases the levels of retromer proteins, shifts amyloid-precursor protein (APP) away from the endosome, and decreases the pathogenic processing of APP. TPT-260 inhibits TLR4 upregulation, IKKβ phosphorylation, NF-κB p65 nuclear translocation, and NLRP3 inflammasome formation. TPT-260 improves retromer-mediated cargo trafficking, reduces brain infarct area, and decreases amyloid plaque deposition. TPT-260 exhibits minimal cytotoxicity to primary microglia at tested concentrations. TPT-260 can be used for the research of inflammatory bowel disease, ischemic stroke and Alzheimer's disease^[1][2][3][4].

TPT-260 (10 μM) improves Occludin recycling and epithelial barrier function in Caco-2 cells but has no effect on VMP1-knockdown Caco-2 cells, indicating VMP1 is required for the Target Reagent's activity^[1].
TPT-260 (5-20 μM) has no cytotoxic effect on primary mouse microglia, as measured by cell viability and LDH release assays^[2].
TPT-260 (5-20 μM) protects primary mouse microglia from LPS (HY-D1056)/Nigericin (HY-127019)-induced cytotoxicity, as shown by restored cell viability and reduced LDH release^[2].
TPT-260 (5-20 μM) inhibits LPS/Nigericin-induced inflammasome formation in primary mouse microglia, as measured by reduced ASC speck formation^[2].
TPT-260 (5-20 μM) inhibits LPS/Nigericin-induced nuclear translocation of NF-κB p65 in primary mouse microglia, as measured by reduced nuclear p65 fluorescence intensity^[2].
TPT-260 (5-20 μM) inhibits LPS (HY-D1056)/Nigericin (HY-127019)-induced upregulation of pro-inflammatory gene expression (Nlrp3, Tnfa, Il1b) in primary mouse microglia^[2].
TPT-260 (5-20 μM) attenuates LPS/Nigericin-induced activation of the TLR4-IKKβ-NF-κB pathway in primary mouse microglia, as shown by reduced levels of pathway-related proteins and pro-inflammatory IL-1β^[2].
TPT-260 (5 μM; 48 h) increases plasma membrane expression of NHE3 in Caco-2/bbe cells, raising surface NHE3 to 142.4% of control^[3].
TPT-260 (5 μM; 48 h) increases levels of core retromer proteins VPS35 and VPS26 in Caco-2/bbe cells, and prevents the Cholera toxin (CT)-induced reduction in these retromer proteins when given either concurrently with CT or prior to CT exposure^[3].
TPT-260 (5 μM; 48 h) increases plasma membrane expression of NHE3 in polarized Caco-2/bbe-HA-NHE3 cells, and reverses the CT-induced reduction in NHE3 surface expression when given either concurrently with CT or prior to CT exposure^[3].
TPT-260 (5 μM; 48 h) partially reduces forskolin-induced fluid secretion in 3D human duodenal enteroids by stimulating NHE3-mediated fluid absorption^[3].
TPT-260 (R55) binds to retromer complex with a K_d of ~5 μM^[4].
TPT-260 (48 h) increases Vps35 levels with an EC₅₀ of ~3.3 μM in primary hippocampal neurons^[4].
TPT-260 (48 h) significantly reduces the levels of both endogenous Aβ40 and Aβ42 in hippocampal neurons^[4].
TPT-260 inhibits Aβ levels with an IC₅₀ of ~12 μM in hippocampal neurons^[4].
TPT-260 significantly reduces the levels of both endogenous β-CTF and sAPPβ, and increases sAPPα levels in hippocampal neurons^[4].

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

TPT-260 (5 mg/kg; i.p.; single dose 24 hours prior to MCAO surgery) significantly reduces brain infarct volume, lowers neuroinflammatory marker levels, and improves neurological function in ischemic stroke model mice by inhibiting NF-κB signaling and M1 microglial activation^[2].

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

260.40

C₈H₁₂N₄S₃

769856-81-7

NC(SCC1=CC=C(CSC(N)=N)S1)=N

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Zhao J, et al. Loss of VMP1 Impairs Tight Junction Recycling and Aggravates Intestinal Barrier Dysfunction in Inflammatory Bowel Disease. Adv Sci (Weinh). Published online February 27, 2026.  [Content Brief]

  [2]. Qian J, et al. Therapeutic Potential of TPT-260 in Ischemic Stroke: An Investigation Into Its Anti-Inflammatory Effects and Impact on Microglial Activation. J Inflamm Res. 2025 Mar 1;18:3055-3066.  [Content Brief]

  [3]. Singh V, et al. Cholera toxin inhibits SNX27-retromer-mediated delivery of cargo proteins to the plasma membrane. J Cell Sci. 2018;131(16):jcs218610. Published 2018 Aug 17.  [Content Brief]

  [4]. Mecozzi VJ, et al. Pharmacological chaperones stabilize retromer to limit APP processing. Nat Chem Biol. 2014 Jun;10(6):443-9.  [Content Brief]