molt-3

TJ191 is a selective anti-cancer agent, targeting low TβRIII-expressing malignant T-cell leukemia lymphoma cells.

Myriceric acid B is a potent HIV-1 entry inhibitor targeting gp41 and a lead compound for developing novel anti-HIV-1 drugs. It scavenges DPPH free radicals with an IC50 value of 21.8 μM, inhibits aromatase activity with an IC50 value of 6.8 μM, and exhibits cytotoxic activity towards the MOLT-3 cell line with an IC50 value of 3.9 μM.

5-Bromouridine is a brominated analog of the nucleoside uridine .1It can be incorporated into RNA and subsequently detected by antibodies against bromodeoxyuridine .25-Bromouridine decreases the viability of HL-60 and MOLT-4 cells (LC50s = 10 and 20 μM, respectively). It induces apoptosis and halts the cell cycle at the S phase in HL-60 cells. It is photoreactive, and UV irradiation has been used to cross-link RNA containing 5-bromouridine to proteins in the study of of RNA-protein interactions.1,35-Bromouridine can also be incorporated into RNA using 5-bromouridine 5'-triphosphate . 1.Tanner, N.K., Hanna, M.M., and Abelson, J.Binding interactions between yeast tRNA ligase and a precursor transfer ribonucleic acid containing two photoreactive uridine analoguesBiochemistry27(24)8852-8861(1988) 2.Li, X., Patel, R., Melamed, M.R., et al.The cell cycle effects and induction of apoptosis by 5-bromouridine in cultures of human leukaemic MOLT-4 and HL-60 cell lines and mitogen-stimulated normal lymphocytesCell Prolif.27(6)307-319(1994) 3.Gott, J.M., Willis, M.C., Koch, T.H., et al.A specific, UV-induced RNA-protein cross-link using 5-bromouridine-substituted RNABiochemistry30(25)6290-6295(1991)

Nornidulin is a depsidone originally isolated from [A. nidulans] with antibacterial activity against [M. tuberculosis] and [M. ranoe], and antifungal activity against [T. tonsurans] and [M. audouini]. It inhibits the growth of methicillin-resistant [S. aureus] (MRSA; MIC = 2 μg ml) and has larvicidal activity toward Artemia (LC50 = 1.7 μg ml). Nornidulin exhibits cytotoxic activity in MOLT-3 cells (IC50 = 35.7 μM) but not in HuCCA-1, HepG2, or A549 cells (IC50s = >116.4 μM).

Cyclopentenylcytosine (CPC), a nucleoside analog, effectively inhibits CTP synthetase, leading to reduced levels of cytidine triphosphate (CTP) and deoxycytidine triphosphate (dCTP) in leukemic cells. Furthermore, it enhances the phosphorylation of 1-β-D-arabinorubosylmannosylcytidine (araC) and increases its DNA intercalation activity. In the human T lymphocyte line MOLT-3, cyclopentenylcytosine triggers apoptosis and necrosis in a dose (50-300 nM) and time (8-16 h) dependent manner. When used in conjunction with araC, cyclopentenylcytosine augments the induction of both apoptosis and necrosis, amplifying its cytotoxic effects on T lymphoblasts.

Nidulin is a depsidone originally isolated from A. nidulans. It is active against the bacteria M. tuberculosis and M. ranoe, as well as the fungi T. tonsurans and M. audouini. It also inhibits the growth of methicillin-resistant S. aureus (MRSA; MIC = 4 μg/ml) and has larvicidal activity toward Artemia (LC50 = 2.8 μg/ml). Nidulin is cytotoxic to MOLT-3 cells (IC50 = 21.2 μM) but not HuCCA-1, HepG2, or A549 cells (IC50s = >112.7 μM). It inhibits aromatase with an IC50 value of 11.2 μM.

KZR-616, a first-in-class inhibitor of the immunoproteasome, selectively targets the LMP7 (IC50: 39/57 nM=hLMP7/mLMP7) and LMP2 (IC50: 131/179 nM=hLMP7/mLMP7) subunits of the immunoproteasome. KZR-616 has the potential for the research of multiple autoimmune diseases[1][2]. KZR-616 also inhibits MECL-1 subunit (IC50=623 nM) and constitutive proteasome β5 subunit (IC50=688 nM). KZR-616 maintains LMP7 and LMP2 selective inhibition in MOLT-4 cells. KZR-616 (250 nM) shows a comparable cytokine inhibition profile peripheral blood mononuclear cells (PBMC)[1].KZR-616 is an immunoproteasome-selective inhibitor identified based on the optimization of ONX-0914 and PR-924 [3]. KZR-616 (5 mg/kg; i.v.; dosing was repeated on days 6, 8, 11, and 13) shows efficacy in the anticollagen antibody induced arthritis (CAIA) model[1]. [1]. Johnson HWB, et al. Required Immunoproteasome Subunit Inhibition Profile for Anti-Inflammatory Efficacy and Clinical Candidate KZR-616 ((2 S,3 R)- N-(( S)-3-(Cyclopent-1-en-1-yl)-1-(( R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)-3-hydroxy-3-(4-methoxyphenyl)-2-(( S)-2-(2-morpholinoacetamido)propanamido)propenamide). J Med Chem. 2018 Dec 27;61(24):11127-11143. [2]. Muchamuel T, et al. FRI0296 Kzr-616, a selective inhibitor of the immunoproteasome, blocks the disease progression in multiple models of systemic lupus erythematosus (SLE). Annals of the Rheumatic Diseases 2018;77:685. [3]. Xi J, et al. Immunoproteasome-selective inhibitors: An overview of recent developments as potential drugs for hematologic malignancies and autoimmune diseases. Eur J Med Chem. 2019;182:111646.

6β,7β-Epoxyasteriscunolide A, a sesquiterpenoid, exhibits cytotoxicity against HL-60 and MOLT-3 leukemia cell lines, with half maximal inhibitory concentrations (IC50s) ranging from 4.1 to 5.4 μM [1].