PAI-1-IN-1 is an orally active and specific PAI-1 inhibitor with an IC50 of <6.95 μM. PAI-1-IN-1 blocks the interaction between PAI-1 and serine proteases or LRP-1, and enhances plasmin generation. PAI-1-IN-1 restores macrophage efferocytosis and promotes macrophage polarization. PAI-1-IN-1 alleviates PAI-1 -mediated inhibition of Furin, promotes MT1-MMP maturation, activates the NOTCH1 signaling pathway, inhibits proliferation and induces apoptosis. PAI-1-IN-1 promotes skeletal muscle regeneration and alleviates inflammation in a mouse model of skeletal muscle injury. PAI-1-IN-1 can be used in research on skeletal muscle injury-induced inflammation and chronic myeloid leukemia [1] [2].
In Vivo, PAI-1-IN-1 (10 mg/kg; p.o.; daily; for 3-7 consecutive days) promotes skeletal muscle regeneration and alleviates inflammation in a cardiotoxin (CTX)-induced mouse model of skeletal muscle injury by downregulating pro-inflammatory cytokine expression, upregulating anti-inflammatory cytokine expression, and accelerating tissue repair. It enhances the phagocytic activity of macrophages (as a surrogate marker of efferocytosis), increasing the dextran uptake rate of macrophages by 14.5 percentage points[1].
In Vitro, PAI-1-IN-1 (2 h) enhances efferocytosis in mouse bone marrow-derived CCR2+Ly6C+ macrophages and J774.1-GFP cells via an LRP-1-dependent mechanism[1]. PAI-1-IN-1 (62.7 μM; 72 h) exerts direct anti-tumor effects on PAI-1/K562-1 and PAI-1/K562-2 chronic myeloid leukemia cells by inhibiting proliferation, inducing apoptosis, and regulating the Furin/NICD signaling pathway[2]. PAI-1-IN-1 upregulates the protein expression level of Furin and enhances the expression level of MT1-MMP on the cell surface[2].
References:
[1]. Ibrahim AA, et al. Inflammatory macrophage-derived plasminogen activator inhibitor-1 exacerbates inflammation through efferocytosis inhibition. Cell Death Discov. 2026;12(1):195. Published 2026 Mar 27.
[2]. Sasaki K, et al. TM5614, an Inhibitor of Plasminogen Activator Inhibitor-1, Exerts an Antitumor Effect on Chronic Myeloid Leukemia. Tohoku J Exp Med. 2022;257(3):211-224.
In Vivo, PAI-1-IN-1 (10 mg/kg; p.o.; daily; for 3-7 consecutive days) promotes skeletal muscle regeneration and alleviates inflammation in a cardiotoxin (CTX)-induced mouse model of skeletal muscle injury by downregulating pro-inflammatory cytokine expression, upregulating anti-inflammatory cytokine expression, and accelerating tissue repair. It enhances the phagocytic activity of macrophages (as a surrogate marker of efferocytosis), increasing the dextran uptake rate of macrophages by 14.5 percentage points[1].
In Vitro, PAI-1-IN-1 (2 h) enhances efferocytosis in mouse bone marrow-derived CCR2+Ly6C+ macrophages and J774.1-GFP cells via an LRP-1-dependent mechanism[1]. PAI-1-IN-1 (62.7 μM; 72 h) exerts direct anti-tumor effects on PAI-1/K562-1 and PAI-1/K562-2 chronic myeloid leukemia cells by inhibiting proliferation, inducing apoptosis, and regulating the Furin/NICD signaling pathway[2]. PAI-1-IN-1 upregulates the protein expression level of Furin and enhances the expression level of MT1-MMP on the cell surface[2].
References:
[1]. Ibrahim AA, et al. Inflammatory macrophage-derived plasminogen activator inhibitor-1 exacerbates inflammation through efferocytosis inhibition. Cell Death Discov. 2026;12(1):195. Published 2026 Mar 27.
[2]. Sasaki K, et al. TM5614, an Inhibitor of Plasminogen Activator Inhibitor-1, Exerts an Antitumor Effect on Chronic Myeloid Leukemia. Tohoku J Exp Med. 2022;257(3):211-224.