BMMP is an anti- HIV-1 agent and hnRNP M modulator. BMMP modulates hnRNP M function to suppress CD44 mRNA expression. BMMP induces abnormal uncoating of the HIV viral core at the post-entry step. BMMP suppresses migration of TGF-β -stimulated lung carcinoma cells. BMMP suppresses HIV-1 reverse transcription and replication without inhibiting virion release. BMMP exerts anti-HIV-1 activity via a mechanism distinct from CA protein-binding heterocyclic compounds. BMMP can be used for the research of human immunodeficiency virus infection and non-small cell lung cancer [1] [2].
In Vitro, BMMP (20 μM; 2 d) does not reduce the viability of 293T or M8166 cells[1]. BMMP (20 μM; 3 d) inhibits full-cycle HIV-1 replication across 293T and M8166 cells to 30% of control levels[1]. BMMP (20 μM) does not affect the release of HIV-1 virions from 293T cells[1]. BMMP (20 μM; 1 d) does not significantly alter the infectivity of HIV-1 virions produced by 293T cells[1]. BMMP (20 μM; 1 d) potently inhibits early-phase HIV-1 infectivity in M8166 cells to less than 10% of control levels[1]. BMMP (20 μM; 2 d) does not affect HIV-1 reverse transcription but suppresses nuclear localization and integration of viral DNA in 293T cells, reducing 2-LTR DNA to 60% and Alu-LTR DNA to 46% of control levels[1]. BMMP (20 μM; 1 d) destabilizes HIV-1 CA protein in infected HeLa cells[1]. BMMP (20 μM; 1 d) does not change the nuclear localization of hnRNP M but reduces HIV-1 CA protein levels in infected HeLa cells[1]. BMMP (20 μM; 1 d) inhibits early-phase HIV-1 infectivity in both control and hnRNP M-knockdown HeLa cells, indicating hnRNP M is not involved in BMMP's anti-HIV activity[1]. BMMP (0.1-100 μM; 2 d) at 0.1-50 μM does not reduce A549 cell viability, while 100 μM BMMP shows mild toxicity[1]. BMMP (0.1-100 μM; 24 h total incubation with TGF-β stimulation) inhibits TGF-β-induced migration of A549 cells in a concentration-dependent manner, with near-complete inhibition at 20 μM[1]. BMMP (20 μM; 1 h, 3 h, 6 h, or 1 d incubation with TGF-β stimulation) slightly reduces vimentin mRNA levels but does not inhibit TGF-β-induced EMT marker changes in A549 cells[1]. BMMP (20 μM; 1 d incubation with TGF-β stimulation) reduces TGF-β-induced increases in CD44s, CD44v8, and CD44v10 mRNA levels in A549 cells[1]. BMMP (20 μM; 1 d incubation with TGF-β stimulation) reduces TGF-β-induced CD44 mRNA expression in A549 cells via hnRNP M, as the effect is abolished in hnRNP M-knockdown cells[1]. BMMP (20 μM; up to 100 hours) inhibits replication of HIV-1 NL4-3 strain in human T-lymphoblastoid M8166 cells[2]. BMMP does not directly interact with HIV-1 Pr55Gag or CA protein in a cell-free surface plasmon resonance assay[2].
References:
[1]. Kamo M, et al. Discovery of anti-cell migration activity of an anti-HIV heterocyclic compound by identification of its binding protein hnRNP M. Bioorg Chem. 2021;107:104627.
[2]. Kamo M, et al. Synthesis of the biotinylated anti-HIV compound BMMP and the target identification study. Bioorg Med Chem Lett. 2016;26(1):43-45.
In Vitro, BMMP (20 μM; 2 d) does not reduce the viability of 293T or M8166 cells[1]. BMMP (20 μM; 3 d) inhibits full-cycle HIV-1 replication across 293T and M8166 cells to 30% of control levels[1]. BMMP (20 μM) does not affect the release of HIV-1 virions from 293T cells[1]. BMMP (20 μM; 1 d) does not significantly alter the infectivity of HIV-1 virions produced by 293T cells[1]. BMMP (20 μM; 1 d) potently inhibits early-phase HIV-1 infectivity in M8166 cells to less than 10% of control levels[1]. BMMP (20 μM; 2 d) does not affect HIV-1 reverse transcription but suppresses nuclear localization and integration of viral DNA in 293T cells, reducing 2-LTR DNA to 60% and Alu-LTR DNA to 46% of control levels[1]. BMMP (20 μM; 1 d) destabilizes HIV-1 CA protein in infected HeLa cells[1]. BMMP (20 μM; 1 d) does not change the nuclear localization of hnRNP M but reduces HIV-1 CA protein levels in infected HeLa cells[1]. BMMP (20 μM; 1 d) inhibits early-phase HIV-1 infectivity in both control and hnRNP M-knockdown HeLa cells, indicating hnRNP M is not involved in BMMP's anti-HIV activity[1]. BMMP (0.1-100 μM; 2 d) at 0.1-50 μM does not reduce A549 cell viability, while 100 μM BMMP shows mild toxicity[1]. BMMP (0.1-100 μM; 24 h total incubation with TGF-β stimulation) inhibits TGF-β-induced migration of A549 cells in a concentration-dependent manner, with near-complete inhibition at 20 μM[1]. BMMP (20 μM; 1 h, 3 h, 6 h, or 1 d incubation with TGF-β stimulation) slightly reduces vimentin mRNA levels but does not inhibit TGF-β-induced EMT marker changes in A549 cells[1]. BMMP (20 μM; 1 d incubation with TGF-β stimulation) reduces TGF-β-induced increases in CD44s, CD44v8, and CD44v10 mRNA levels in A549 cells[1]. BMMP (20 μM; 1 d incubation with TGF-β stimulation) reduces TGF-β-induced CD44 mRNA expression in A549 cells via hnRNP M, as the effect is abolished in hnRNP M-knockdown cells[1]. BMMP (20 μM; up to 100 hours) inhibits replication of HIV-1 NL4-3 strain in human T-lymphoblastoid M8166 cells[2]. BMMP does not directly interact with HIV-1 Pr55Gag or CA protein in a cell-free surface plasmon resonance assay[2].
References:
[1]. Kamo M, et al. Discovery of anti-cell migration activity of an anti-HIV heterocyclic compound by identification of its binding protein hnRNP M. Bioorg Chem. 2021;107:104627.
[2]. Kamo M, et al. Synthesis of the biotinylated anti-HIV compound BMMP and the target identification study. Bioorg Med Chem Lett. 2016;26(1):43-45.