MeTC7

MeTC7 is a vitamin D receptor (VDR) antagonist (IC₅₀=2.9μM). MeTC7 blocks VDR/RXRα, VDR/MYCN and VDR/PD-L1 signaling. MeTC7 inhibits tumor cell viability, colony formation and PD-L1 expression. MeTC7 can be used in research on neuroblastoma, ovarian cancer, acute myeloid leukemia and other tumors, as well as tumor immunotherapy^[1-4].

In vitro, treatment with 100-500nM MeTC7 for 48 hours reduced PD-L1 protein level, reduced cell viability, and reduced colony number and size in AML-1, MV-411 and THP-1 cells^[5]. Treatment with 100-500nM MeTC7 for 48 hours reduced PD-L1 surface expression and reduced cell viability in PANC-1 cells, KCKO cells and ES2 cells^[6]. Pretreatment with 10μM MeTC7 for 30 minutes followed by electric pulse stimulation for 24 hours increased IL-6 mRNA expression, increased p-STAT3/STAT3 ratio, and increased myostatin and C/EBPδ mRNA expression in C2C12 cells^[7].

In vivo, intraperitoneal injection of 10mg/kg MeTC7 for 7 days slowed tumor growth in NSG mice subcutaneously inoculated with ES2, SKOV-3 or D283 cells^[8]. Intraperitoneal injection of 10mg/kg MeTC7 three times weekly for 4 weeks increased the proportion of spleen Th17 cells and CD4⁺RORyt⁺ cells, elevated serum IL-17A and IL-22 levels, upregulated prostate RORyt mRNA expression, promoted prostate inflammatory cell infiltration, and reduced prostate VDR and p-ERK1/2 expression in NOD mouse experimental autoimmune prostatitis mode^l[9].

References:

[1] Liang L, Ruan Y, Yu X, et al. DKS26 Alleviates Ischemia-Reperfusion Injury-Induced Acute Kidney Injury by Stabilizing Vitamin D Receptors to Inhibit the Inflammatory Pathway of NF-κB P65. Int J Mol Sci. 2025 Mar 25;26(7):2985.

[2] Lee TW, Lee TI, Higa S, et al. Calcitriol deficiency reduces myocardial ATP production with disturbed mitochondrial dynamics and increased uncoupling protein 2 expression. Eur J Pharmacol. 2025 Sep 5;1002:177858.

[3] Dong L, Gao Y, Li Q, et al. Betulinic Acid Enema Alleviates Colitis by Targeting Vitamin D Receptor to Protect the Intestinal Mucosal Barrier and Modulate Mucosa-Associated Microbiota. Phytother Res. 2026 Jun 18.

[4] Isaac I, Patel L, Tran N,et al. Reengineering Endogenous Targeting Lipid Nanoparticles (ENDO) for Systemic Delivery of mRNA to Pancreas. Adv Mater. 2025 Oct;37(40):e2507657.

[5] Khazan N, Quarato ER, Singh NA, et al. Vitamin D Receptor Antagonist MeTC7 Inhibits PD-L1. Cancers. 2023 Jun 30;15(13):3432.

[6] Singh RK, Kim K, Rowswell-Turner RB, et al. Targeting Vitamin-D receptor(VDR) by a small molecule antagonist MeTC7 inhibits PD-L1 but controls TH-MYCN neuroblastoma growth PD-L1 independently. bioRxiv. 2020 Aug 17:2020.08.16.252940.

[7] Hashimoto S, Hosoi T, Yakabe M, et al. Exercise-induced vitamin D receptor and androgen receptor mediate inhibition of IL-6 and STAT3 in muscle. Biochem Biophys Rep. 2024;37:101621.

[8] Khazan N, Kim KK, Hansen JN, et al. Identification of a Vitamin-D Receptor Antagonist, MeTC7, which Inhibits the Growth of Xenograft and Transgenic Tumors In Vivo. J Med Chem. 2022 Apr 28;65(8):6039-55.

[9] Niu D, Yue SY, Wang X, et al. A high-glucose diet aggravates experimental autoimmune prostatitis via DHVD3/VDR/ERK axis-mediated Th17 differentiation. Asian J Androl. 2026;28:1-11.