The invention features compounds (e.g., macrocyclic compounds) capable of modulating biological processes, for example through binding to a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein (e.g., a eukaryotic target protein such as a mammalian target protein or a fungal target protein or a prokaryotic target protein such as a bacterial target protein). These compounds bind endogenous intracellular presenter proteins, such as the FKBPs or cyclophilins, and the resulting binary complexes selectively bind and modulate the activity of intracellular target proteins. Formation of a tripartite complex among the presenter protein, the compound, and the target protein is driven by both protein-compound and protein-protein interactions, and both are required for modulation of the targeted protein's activity.

The present invention provides an agent for treating malignant tumor, comprising a compound of formula (1):

##STR00001##

wherein R.sup.1 to R.sup.4 are hydrogen atom, halogen, or etc., Y is optionally-substituted alkylene group or etc.

The present invention provides an agent for treating malignant tumor, comprising a compound of formula (1):

##STR00001##

wherein R.sup.1 to R.sup.4 are hydrogen atom, halogen, or etc., Y is optionally-substituted alkylene group or etc.

The present invention provides an agent for treating malignant tumor, comprising a compound of formula (1): ##STR00001## wherein R.sup.1 to R.sup.4 are hydrogen atom, halogen, or etc., Y is optionally-substituted alkylene group or etc.

The present invention provides an agent for treating malignant tumor, comprising a compound of formula (1): ##STR00001## wherein R.sup.1 to R.sup.4 are hydrogen atom, halogen, or etc., Y is optionally-substituted alkylene group or etc.

The present invention features improved compounds, especially the compound having the structure (1). Compositions and methods of identifying patients having cancer using biomarkers (e.g., PDE3A, PDE3B, SLFN12 and/or CREB3L1) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention.

##STR00001##

In one aspect, the invention relates to compounds having the formula:

##STR00001##

where R.sup.1-R.sup.6, a, b, and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

In one aspect, the invention relates to compounds having the formula:

##STR00001##

where R.sup.1-R.sup.6, a, b, and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

A first compound having an atom in an oxidized state is reacted with a bis(trimethylsilyl) six-membered ring system or related compound to form a second compound having the atom in a reduced state relative to the first compound. The atom in an oxidized state is selected from the group consisting of Groups 2-12 of the Periodic Table, the lanthanides, As, Sb, Bi, Te, Si, Ge, Sn, and Al.

Irreversible inhibitors of G12C mutant K-Ras protein are provided. Also disclosed are methods to modulate the activity of G12C mutant K-Ras protein and methods of treatment of disorders mediated by G12C mutant K-Ras protein.