MYCi361

MYCi361 (NUCC-0196361) is a MYC inhibitor with the Kd of 3.2 μM for binding to MYC. MYCi361 (NUCC-0196361) suppresses tumor growth and enhances anti-PD1 immunotherapy[1].

Research Areas >> Cancer

Signaling Pathways >> Apoptosis >> c-Myc

MYCi361 inhibits the viability of MYC-dependent cancer cells including prostate cancer (MycCaP, LNCaP, and PC3), leukemia (MV4-11), lymphoma (HL-60 and P493-6), and neuroblastoma (SK-N-B2) with low-micromolar IC50 values[1]. Cell Proliferation Assay[1] Cell Line: The prostate cancer (MycCaP, LNCaP, and PC3), leukemia (MV4-11), lymphoma (HL-60 and P493-6), and neuroblastoma (SK-N-B2). Concentration: 1.4-5.0 μM Incubation Time: 5 days Result: IC50s of 2.9, 1.4, 1.6, 2.6, 5.0, 2.1, and 4.9 μM for prostate cancer (MycCaP, LNCaP, and PC3), leukemia (MV4-11), lymphoma (HL-60 and P493-6), and neuroblastoma (SK-N-B2), respectively.

MYCi361 inhibits MYC-dependent tumor growth in vivo. MYCi361 treatment (100 mg/kg/day for 2 days; then 70 mg/kg/day for 9 days) induces tumor regression in FVB or NSG male mice[1]. MYCi361 has moderate terminal elimination half-life of 44 and 20 h for intraperitoneal (i.p.) or oral (p.o.) dosing in mice, respectively[1]. MYCi361 suppresses tumor growth in mice, increases tumor immune cell infiltration, upregulates PD-L1 on tumors, and sensitizes tumors to anti-PD1 immunotherapy. However, MYCi361 demonstrates a narrow therapeutic index. An improved analog, MYCi975 shows better tolerability[1]. Animal Model: FVB or NSG male mice of 6-8 weeks of age and 25 g bearing established MycCaP tumors[1] Dosage: 50 mg/kg and 70 mg/kg Administration: Treatment i.p. initially at 50 mg/kg twice daily for 2 days, then 70 mg/kg/day for 9 days Result: Induced tumor regression. Animal Model: C57BL/6 mice[1] Dosage: 50 mg/kg (Pharmacokinetic analysis) Administration: Treated p.o. or i.p.; 24 hours Result: Intraperitoneal (i.p.) or oral (p.o.) dosing in mice indicated plasma half-lives of 44 and 20 h, respectively, with maximum plasma concentrations (Cmax) of 27,200 ng/mL (46 μM) i.p. and 13,867 ng/mL (23 μM) p.o..

[1]. Han H, et al. Small-Molecule MYC Inhibitors Suppress Tumor Growth and Enhance Immunotherapy. Cancer Cell. 2019 Nov 11;36(5):483-497.e15.