Lysine-specific demethylase 1A (LSD1, also named KDM1A) is a demethylase that can remove methyl groups from histones H3K4me1/2 and H3K9me1/2. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, and is associated with inferior prognosis. Pharmacological inhibition of LSD1 has been reported to significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. This review will present the structural aspects of LSD1, its role in carcinogenesis, a comparison of currently available approaches for screening LSD1 inhibitors, a classification of LSD1 inhibitors, and its potential as a drug target in cancer therapy.

The rhodium(iii) complex 1 was identified as a potent Wee1 inhibitor in vitro and in cellulo. It decreased Wee1 activity and unscheduled mitotic entry, and induced cell damage and death in TP53-mutated triple-negative breast cancer cells. 1 represents a promising scaffold for further development of more potent metal-based Wee1 antagonists.

Metalation of 2,6-lutidine-functionalized bis(phosphoranimines) (Me3SiNPPr i 2CH2)2C5H3N-2,6 (2) using MgBu2 in THF yielded the magnesium compound [Mg{(Me3SiNPPr i 2CH)2C5H3N-2,6}THF] (3). Further reaction of 3 with 1 equiv of SnCl2 afforded the tin(II) compound [{2-{Sn{C(Pr i 2PNSiMe3)}}-6-{Sn{CH(Pr i 2PNSiMe3)}Cl}}C5H3N]2 (4). Treatment of 2 with 2 equiv of Pb{N(SiMe3)2}2 afforded the lead(II) compound [{2-{Pb{C(Pr i 2PNSiMe3)}}-6-{Pb{CH(Pr i 2PNSiMe3)}N(SiMe3)2}}C5H3N]2 (5). X-ray structural analysis revealed that 4 and 5 consist of a 1,3-dimetallacyclobutane and two metal(II) alkyl moieties. Similar reaction of 3 with 1 equiv of GeCl2(dioxane), however, yielded the germanium(II) compound (6) without forming a similar 1,3-digermacyclobutane ring.

In the literature, very few ytterbium(III) complexes have been reported to display promising anti-cancer activities without photoactivation or conjugation to cytotoxic counterparts/radionuclides. By employing porphyrinato ligands, which provide a rigid molecular scaffold for the ytterbium(III) ion and enhance cellular-uptake efficacy, we have prepared and structurally characterized a series of ytterbium(III) porphyrin complexes showing potent anti-cancer activities with cytotoxic IC 50 values down to the sub-micromolar range. The notable example is an ytterbium(III) octaethylporphyrin complex (1) which exists as a dimeric hydroxyl-bridged complex [Yb 2 (OEP) 2 (m-OH) 2 ] (where H 2 OEP ¼ octaethylporphyrin) in CH 2 Cl 2 solution and in solid state, and as monomeric [Yb(OEP)(DMSO)(OH)(OH 2 )] in DMSO/aqueous solution. Unlike various anti-cancer lanthanide complexes which are proposed to target cellular DNA, transcriptomics data, bioinformatics connectivity map analysis and biochemical experiments altogether indicate that 1 exerts its anti-cancer effect through apoptosis that is highly associated with the endoplasmic reticulum stress pathway.