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. 2022 Apr 11;12(4):57.
doi: 10.1038/s41408-022-00664-y.

The preclinical efficacy of the novel hypomethylating agent NTX-301 as a monotherapy and in combination with venetoclax in acute myeloid leukemia

Byungho Lim  1 , Dabin Yoo  2 , Younghwa Chun  3 , Areum Go  3 , Kyung-Jin Cho  2 , Daeun Choi  2 , Myoung Eun Jung  2 , Ha Young Lee  3 , Rebecca J Boohaker  4 , Jin Soo Lee  3 , DooYoung Jung  3 , Gildon Choi  5
Affiliations

The preclinical efficacy of the novel hypomethylating agent NTX-301 as a monotherapy and in combination with venetoclax in acute myeloid leukemia

Byungho Lim et al. Blood Cancer J. .
No abstract available

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Conflict of interest statement

All researchers from the KRICT received research funds from Pinotbio Inc. DJ is the CEO, and YC, AG, HYL, and JSL are employees of Pinotbio Inc.

Figures

Fig. 1
Fig. 1. Preclinical models of AML demonstrated the improved therapeutic index of NTX-301.
A, B A Kaplan–Meier plot of the survival probability (A) and a plot showing times to endpoint (moribund or the last day of study) (B) of female NOD/SCID mice bearing MV4-11 tumors (n = 8 per group, six groups) upon treatment with NTX-301 [(1.5, 2.0, or 2.5 mg/kg) (p.o.)], DAC [(2.5 mg/kg) (i.p.)], or AZA [5.0 mg/kg (i.p.)]. C, D Tumor growth measured by the quantification of bioluminescence emission (photons/sec) (C) and bioluminescence images on day 42 (D) in female NOD/SCID mice bearing MV4-11 tumors (n = 8 per group, three groups) upon treatment with NTX-301 [(2.0 mg/kg) (p.o.)] or AZA [(5.0 mg/kg) (i.p.)]. E, F Bioluminescence images (E) and quantification of bioluminescence emission (photons/sec) (F) of female NOD/SCID mice (n = 6 per group, four groups) bearing luciferase-labeled MV4-11 tumors upon treatment with NTX-301 [(daily at 1.0 or 2.0 mg/kg) or 2x daily at 1.0 mg/kg (p.o.)]. G–I Tumor growth (G), cell number per gram tumor (H), and anti-CD33 staining intensity (I) of female NMRI nude mice bearing subcutaneous MOLM-13 tumors (n = 6 per group, five groups) upon NTX-301 treatment [(0.2, 0.4, 0.8, or 1.5 mg/kg) (i.p.)]. In G, the red arrows denote the time points of NTX-301 treatment. AZA azacitidine, DAC decitabine, NTX NTX-301; mpk mg/kg, p.o. oral administration, i.p. intraperitoneal administration. P-values (vs. vehicle) are specified and marked as follows: *p < 0.05; **p < 0.001; ***p < 0.0001.
Fig. 2
Fig. 2. NTX-301 conferred benefits in combination with VCX.
A GSEA plots showing significant enrichment of genes regulating sensitivity or resistance to VCX among transcriptome changes induced by 48 h of treatment with NTX-301 or DAC in MV4-11 cells. B Line plots showing the survival (%) of parental (Con) and TP53-knockdown (shp53) MV4-11 cells upon treatment with NTX-301 + VCX (left) or DAC + VCX (right) for 72 h. C Matrices showing the combination index (CI) values upon treatment with NTX-301+VCX or DAC + VCX for 72 h at the indicated concentrations in parental (top) and TP53-knockdown (bottom, shp53) MV4-11 cells. CI values < 1 (blue) indicate synergistic drug combination; darker blue colors are correlated with stronger the synergism, and CI values > 1 (gray) indicate no synergism. D Growth of MV4-11 tumors subcutaneously implanted into female BALB/c nude mice (n = 5 per group, eight groups) upon treatment with NTX-301 or AZA as a monotherapy or in combination with VCX. E Kaplan–Meier curves showing the survival probabilities of female NCG mice (n = 8 per group, six groups) intravenously injected with MV4-11 cells upon treatment with NTX-301 or AZA as a monotherapy or in combination with VCX. AZA azacitidine, DAC decitabine, NTX NTX-301, VCX venetoclax. *p < 0.05; **p < 0.01; ***p < 0.001.
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