TNG917 is a potent, selective EHMT1/2 inhibitor with oral activity. TNG917 reduces H3K9me2 -mediated transcriptional repression, restores interferon-stimulated gene expression, promotes the secretion of T-cell chemokines such as CXCL10, and converts immunologically cold tumors into T-cell inflamed tumors. TNG917 is applicable to studies on immunologically cold tumors, colorectal cancer, anti-tumor immunity, interferon signaling pathways and epigenetic immune escape [1] [2].
In Vivo, TNG917 (3-30 mg/kg, p.o.; once daily) inhibits the growth of HT29 human colon cancer xenografts in immunodeficient NOG mice, with tumor growth inhibition rates of approximately 50% and 84% observed in the 10 and 30 mg/kg dose groups, respectively[1]. TNG917 (10-100 mg/kg, p.o.; once daily for 5 consecutive days) exhibits dose-dependent plasma exposure in female C57BL/6 mice bearing MC38 tumors, and reduces H3K9me2 levels in tumor tissues at 2 and 8 h after the final administration[1]. Combination treatment with TNG917 (3, 30 mg/kg, p.o.; once daily for 6 consecutive days) and Pembrolizumab (10 mg/kg, i.p.; once weekly for a total of 3 times) increases the infiltration of total T cells, CD8+ T cells, CD4+ T cells and M1 macrophages, and reduces M2 macrophages within CT26 tumors[1]. Combination treatment with TNG917 (30 mg/kg, p.o.) and Pembrolizumab (10 mg/kg, i.p.) induces chemokines such as Ccl8, Ccl5 and Ccl3, as well as interferon-stimulated gene-related signals in CT26 tumor tissues[1].
In Vitro, TNG917 dose-dependently reduces H3K9me2 levels in cells, with a cellular potency IC50 of approximately 2 nM, and induces CXCL10 secretion with an AC50 of approximately 5 nM[1]. TNG917 (1-10 μM) is a selective inhibitor of EHMT1/2, and exerts no significant inhibitory effect on the other 37 tested methyltransferases at concentrations of 1 μM and 10 μM[1]. TNG917 relieves H3K9-mediated transcriptional repression, restores the expression of interferon-stimulated genes, and induces the secretion of T cell chemokines such as CXCL10[2]. TNG917 (1 μM) upregulates interferon-stimulated genes in human colorectal cancer cell line HT29, mimicking the phenotype of EHMT1/2 double knockout[1].
References:
[1]. Lu A, et al. TNG917 is a clinical-grade, potent and selective inhibitor of EHMT1/2 for the treatment of immune cold tumors. Poster Abstract 3242. 2024.
[2]. Lu AZ, et al. TNG917 is a Potent and Selective Inhibitor of Histone Lysine Methyltransferases EHMT1/2 that Enhances Anti-Tumor Immunity and Immunotherapy Efficacy. Cancer research. 2026 Jun 10.
In Vivo, TNG917 (3-30 mg/kg, p.o.; once daily) inhibits the growth of HT29 human colon cancer xenografts in immunodeficient NOG mice, with tumor growth inhibition rates of approximately 50% and 84% observed in the 10 and 30 mg/kg dose groups, respectively[1]. TNG917 (10-100 mg/kg, p.o.; once daily for 5 consecutive days) exhibits dose-dependent plasma exposure in female C57BL/6 mice bearing MC38 tumors, and reduces H3K9me2 levels in tumor tissues at 2 and 8 h after the final administration[1]. Combination treatment with TNG917 (3, 30 mg/kg, p.o.; once daily for 6 consecutive days) and Pembrolizumab (10 mg/kg, i.p.; once weekly for a total of 3 times) increases the infiltration of total T cells, CD8+ T cells, CD4+ T cells and M1 macrophages, and reduces M2 macrophages within CT26 tumors[1]. Combination treatment with TNG917 (30 mg/kg, p.o.) and Pembrolizumab (10 mg/kg, i.p.) induces chemokines such as Ccl8, Ccl5 and Ccl3, as well as interferon-stimulated gene-related signals in CT26 tumor tissues[1].
In Vitro, TNG917 dose-dependently reduces H3K9me2 levels in cells, with a cellular potency IC50 of approximately 2 nM, and induces CXCL10 secretion with an AC50 of approximately 5 nM[1]. TNG917 (1-10 μM) is a selective inhibitor of EHMT1/2, and exerts no significant inhibitory effect on the other 37 tested methyltransferases at concentrations of 1 μM and 10 μM[1]. TNG917 relieves H3K9-mediated transcriptional repression, restores the expression of interferon-stimulated genes, and induces the secretion of T cell chemokines such as CXCL10[2]. TNG917 (1 μM) upregulates interferon-stimulated genes in human colorectal cancer cell line HT29, mimicking the phenotype of EHMT1/2 double knockout[1].
References:
[1]. Lu A, et al. TNG917 is a clinical-grade, potent and selective inhibitor of EHMT1/2 for the treatment of immune cold tumors. Poster Abstract 3242. 2024.
[2]. Lu AZ, et al. TNG917 is a Potent and Selective Inhibitor of Histone Lysine Methyltransferases EHMT1/2 that Enhances Anti-Tumor Immunity and Immunotherapy Efficacy. Cancer research. 2026 Jun 10.