Novel PARP1/2 inhibitor mefuparib hydrochloride elicits potent in vitro and in vivo anticancer activity, characteristic of high tissue distribution.

The approval of poly(ADP-ribose) polymerase (PARP) inhibitor AZD2281 in 2014 marked the successful establishment of the therapeutic strategy targeting homologous recombination repair defects of cancers in the clinic. However, AZD2281 has poor water solubility, low tissue distribution and relatively weak in vivo anticancer activity, which appears to become limiting factors for its clinical use. In this study, we found that mefuparib hydrochloride (MPH) was a potent PARP inhibitor, possessing prominent in vitro and in vivo anticancer activity.

Parallel calibration revisited: the second direction for shrinkage estimation of regression coefficients can be as natural and necessary as the traditional one.

In the traditional framework of multivariate spectroscopic calibration, the most popular method, partial least squares (PLS), shrinks the regression coefficients based on the information of training sample concentrations. Motivated by the concept of parallel calibration, the second direction for shrinkage of regression coefficients, the direction towards unknown sample spectra is investigated in this paper. A different multivariate calibration method, parallel calibration model based on partial least squares, PCPLS is proposed.

Reactions of the dianion [1,1,1-(CO)3-2-Ph-closo-1,2-MnCB9H9]2- with transition-metal cations: facile insertion and then extrusion of cluster vertexes.

The manganacarborane dianion in [N(PPh(3))(2)][NEt(4)][1,1,1-(CO)(3)-2-Ph-closo-1,2-MnCB(9)H(9)] (1b) reacts with cationic transition metal-ligand fragments to give products in which the electrophilic metal groups (M') are exo-polyhedrally attached to the {closo-1,2-MnCB(9)} cage system via three-center two-electron B-H --> M' linkages and generally also by Mn-M' bonds. With {Cu(PPh(3))}(+), the Cu-Mn-Cu trimetallic species [1,6-{Cu(PPh(3))}-1,7-{Cu(PPh(3))}-6,7-(mu-H)(2)-1,1,1-(CO)(3)-2-Ph-closo-1,2-MnCB(9)H(7)] (3a) is formed, whereas reactions with {M'(dppe)}(2+) (M' = Ni, Pd; dppe = Ph(2)PCH(2)CH(2)PPh(2)) give [1,3-{Ni(dppe)}-3-(mu-H)-1,1,1-(CO)(3)-2-Ph-closo-1,2-MnCB(9)H(8)] (5a) and [1,3,6-{Pd(dppe)}-3,6-(mu-H)(2)-1,1,1-(CO)(3)-2-Ph-closo-1,2-MnCB(9)H(7)] (5b), both of which contain M'-Mn bonds. The latter reaction with M' = Pt affords [3,6-{Pt(dppe)}-3,6-(mu-H)(2)-1,1,1-(CO)(3)-2-Ph-closo-1,2-MnCB(9)H(7)] (6), which lacks a Pt-Mn connectivity.