MN 64

MN-64 is a type of flavone that act as a potent and selective tankyrase inhibitor (IC50 = 6 and 72 nM for TNKS1 and TNKS2, respectively). [1]

Tankytase (TNKS) is a member of poly ADP ribose polymerases (PARPs). There are two related homologue, TNKS1 and TNKS2 that are mostly located in the nuclear pore, cytoplasm, mitotic centrosomes and the Golgi apparatus. They involve in cellular functions such as regulation of cell proliferation and promoting telomere elongation in human cells. [1]

During an assay for screening flavone TNKS inhibitors, MN-64 is discovered for abrogating STF luciferase activity at 200nM and potently inhibiting TNKS1 with IC50 of 6nM. It also selectively inhibits TNKS1 and TNKS2 without affecting any other PARPs. Moreover, MN-64 is prominently more selective than other TNKS inhibitors such as XAV939. [1]

Reference:
1.  Narwal M, Koivunen J, Haikarainen T et al. Discovery of tankyrase inhibiting flavones with increased potency and isoenzyme selectivity. J Med Chem. 2013 Oct 24;56(20):7880-9.

Calibration setting numbers for dose calibrators for the PET isotopes (52)Mn, (64)Cu, (76)Br, (86)Y, (89)Zr, (124)I.[Pubmed:27152914]

Appl Radiat Isot. 2016 Jul;113:89-95.

For PET radionuclides, the radioactivity of a sample can be conveniently measured by a dose calibrator. These devices depend on a "calibration setting number", but many recommended settings from manuals were interpolated based on standard sources of other radionuclide(s). We conducted HPGe gamma-ray spectroscopy, resulting in a reference for determining settings in two types of vessels containing one of several PET radionuclides. Our results reiterate the notion that in-house, experimental calibrations are recommended for different radionuclides and vessels.

[Mn(III)Mn(IV)2Mo14O56](17-): A Mixed-Valence Meso-Polyoxometalate Anion Encapsulated by a 64-Nuclearity Silver Cluster.[Pubmed:27362281]

Inorg Chem. 2016 Jul 18;55(14):6833-5.

A 64-nuclearity silver cluster encapsulating a unique POM anion [Mn(III)Mn(IV)2Mo14O56](17-) has been synthesized. The formation of the templating core performs a reassembly process for increasing nuclearities from {MnMo9} to {Mn3Mo14}. It represents a rare inorganic meso anion containing mixed-valent Mn that is built up by d-{Mn(IV)Mo7} and l-{Mn(IV)Mo7} units connecting together through a {Mn(III)} fragment.

The field and temperature dependence of the magnetic and structural properties of the shape memory compound Ni(1.84)Mn(1.64)In(0.52).[Pubmed:22037587]

J Phys Condens Matter. 2011 Nov 16;23(45):456004.

Magnetization and high resolution neutron powder diffraction measurements have been made on the magnetic shape memory alloy Ni(1.84)Mn(1.64)In(0.52). The compound undergoes a broad structural phase transition, which on heating starts at approximately 150 K and finishes at approximately 215 K. On cooling there is a approximately 20 K hysteresis. The high temperature parent phase is cubic (a = 5.988 A) with the L2(1) structure in which the excess Mn atoms occupy the vacancies on the Ni and In sites. The magnetic moment is located mainly on the Mn atoms with the same magnitude on both the 4a (Mn) and 4b (In) sites. The low temperature martensite is monoclinic with parameters a = 4.405(2), b = 5.553(2), c = 12.950(2) A, beta = 86.47(10) degrees and space group P2/m. The magnetic properties of the martensitic phase are complex and indicate metamagnetic behaviour.

Discovery of tankyrase inhibiting flavones with increased potency and isoenzyme selectivity.[Pubmed:24116873]

J Med Chem. 2013 Oct 24;56(20):7880-9.

Tankyrases are ADP-ribosyltransferases that play key roles in various cellular pathways, including the regulation of cell proliferation, and thus, they are promising drug targets for the treatment of cancer. Flavones have been shown to inhibit tankyrases and we report here the discovery of more potent and selective flavone derivatives. Commercially available flavones with single substitutions were used for structure-activity relationship studies, and cocrystal structures of the 18 hit compounds were analyzed to explain their potency and selectivity. The most potent inhibitors were also tested in a cell-based assay, which demonstrated that they effectively antagonize Wnt signaling. To assess selectivity, they were further tested against a panel of homologous human ADP-ribosyltransferases. The most effective compound, 22 (MN-64), showed 6 nM potency against tankyrase 1, isoenzyme selectivity, and Wnt signaling inhibition. This work forms a basis for rational development of flavones as tankyrase inhibitors and guides the development of other structurally related inhibitors.

MN-64 is a potent tankyrase 1 inhibitor, with IC50s of 6 nM, 72 nM, 19.1 μM, and 39.4 μM for TNKS1, TNKS2, ARTD1 and ARTD2, respectively.

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