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In order to obtain noninvasively quantitative static mechanical properties of living tissue, we propose a new type of inverse problem by which the spatial distribution of the relative elastic modulus of the tissue can be estimated only from the deformation or strain measurement. The living tissue is modeled as a linear isotropic incompressible elastic medium which has the spatial distribution of the shear modulus, and the deformation or strain is supposedly measured ultrasonically. Assuming that there is no mechanical source in the region of interest, we derive a set of linear equations in which unknowns are the spatial derivatives of the relative shear modulus, and the coefficients are the strain and its spatial derivatives. By solving these equations, the spatial derivatives of the relative shear modulus are determined throughout the region, from which the spatial distribution of the relative shear modulus is obtained by spatial integration. The feasibility of this method was demonstrated using the simulated deformation data of the simple inclusion problem. The proposed method seems promising for the quantitative differential diagnosis on the lesion in the tissue in vivo.

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We report the discovery of a potent and isozyme-selective MTHFD2 inhibitor, DS18561882 (2). Through investigation of the substituents on our tricyclic coumarin scaffold (1,2,3,4-tetrahydrochromeno­[3,4-c]­pyridin-5-one), MTHFD2 inhibitory activity was shown to be elevated by incorporating an amine moiety at the 8-position and a methyl group at the 7-position of the initial lead 1. X-ray structure analysis revealed that a key interaction for enhanced potency was salt bridge formation between the amine moiety and the diphosphate linker of an NAD+ cofactor. Furthermore, ortho-substituted sulfonamide in place of benzoic acid of 1 significantly improved cell permeability and cell-based growth inhibition against a human breast cancer cell line. The thus-optimized DS18561882 showed the strongest cell-based activity (GI50 = 140 nM) in the class, a good oral pharmacokinetic profile, and thereby tumor growth inhibition in a mouse xenograft model upon oral administration.

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