SHIP1-IN-1 

SHIP1-IN-1 is an orally active, blood-brain barrier-permeable SHIP1 ligand. SHIP1-IN-1 exhibits IC₅₀ values of 384 μM and 177 μM against human SHIP1, and an IC₅₀ value of 379 μM against murine SHIP1. SHIP1-IN-1 alters the binding state of SHIP1 to phosphatidylinositol membranes, and regulates phosphoinositide pools and phosphorylated AKT levels. SHIP1-IN-1 enhances the uptake of myelin/membrane fragments and amyloid proteins by microglia, alters gene expression and reduces IL-1β levels. SHIP1-IN-1 can be used in studies related to Alzheimer's disease^[1][2].

SHIP1-IN-1 (compound 32) inhibits the human two‑domain SHIP1 protein construct with an IC₅₀ of 384 μM, the human five‑domain SHIP1 protein construct with an IC₅₀ of 177 μM, and the murine five‑domain SHIP1 protein construct with an IC₅₀ of 379 μM^[1].
SHIP1-IN-1 (1.0-10 μM) modulates the phosphoinositide association profile of the human five-domain SHIP1 protein, increasing relative binding to PI(3,4)P₂ at higher concentrations^[1].
SHIP1-IN-1 (60 min treatment at 37 °C; 3 min heating at 44.2 °C) engages full-length SHIP1 in HMC3 cells, reducing protein thermal stability with an AC₅₀ of 40.4 μM^[1].
SHIP1-IN-1 (15 min) modulates proximal SHIP1-dependent AKT signaling in IL-4-conditioned THP-1 cells, reducing the pAKT (S473)/tAKT ratio with an IC₅₀ of 4.0 μM and the pAKT (T308)/tAKT ratio with an IC₅₀ of 5.3 μM^[1].
SHIP1-IN-1 enhances pHrodo-myelin/membrane debris uptake in both BV2 murine microglia (EC₅₀ = 0.777 μM) and primary murine microglia (EC₅₀ = 0.484 μM), while reducing cell count and nuclear intensity with IC₅₀ values of 3.45 and 6.46 μM in BV2 cells, and 5.65 and 19.4 μM in primary microglia, respectively^[1].
SHIP1-IN-1 (50 nM-950 μM; 20 min pre-incubation with enzyme, 10 min reaction with substrate) inhibits purified SHIP1 Ptase-C2 domain activity with an IC₅₀ of 302 μM^[2].
SHIP1-IN-1 (Example 9) increases phagocytosis, reduces cell count, and alters nuclear intensity in primary mouse microglia in an in vitro high-content imaging assay^[2].

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

SHIP1-IN-1 (compound 32) (150 mg/kg; p.o.; three times at 12-h intervals) achieves brain exposure that alters IL-1β levels, indicating modulation of microglial activation and neuroinflammation in an amyloidosis mouse model of Alzheimer's disease^[1].

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

368.86

C₂₀H₂₁ClN₄O

3027375-00-1

ClC(C=CC=C1)=C1COC2=CN=CC(C3=CN(C4CCNCC4)N=C3)=C2

Room temperature in continental US; may vary elsewhere.

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

• [1]. Jesudason CD, et al. Optimization and Characterization of SHIP1 Ligands for Cellular Target Engagement and Activity in Alzheimer's Disease Models. bioRxiv [Preprint]. 2026 Jan 2:2025.12.31.697127.

  [2]. Richardson TI, et al. Crizotinib analogues as ship1 inhibitors useful to treat alzheimer's diseases. WO, WO2024015759A1. 2024-01-18.