Abstract: Described herein are MAT2A inhibitors and pharmaceutical compositions comprising said inhibitors. The subject compounds and compositions are useful for the treatment of a disease or disorder associated with MAT2A.

Abstract: The proposed model is a Variational Autoencoder having a learnable prior that is parametrized with a Tensor Train (VAE-TTLP). The VAE-TTLP can be used to generate new objects, such as molecules, that have specific properties and that can have specific biological activity (when a molecule). The VAE-TTLP can be trained in a way with the Tensor Train so that the provided data may omit one or more properties of the object, and still result in an object with a desired property.

Abstract: The disclosure provides for compounds and methods for modulating or inhibiting glutaminyl-peptide cyclotransferase-like protein (QPCTL). In one aspect, described herein are compounds of Formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa) (IIab), (IIba), and (IIbb), stereoisomer thereof, or salts or solvates thereof. Further provided herein are methods of treating a disease or a condition comprising administering a compound of Formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa) (IIab), (IIba), or (IIbb), a stereoisomer thereof, or a salt or solvate thereof.

Abstract: A TLR9 inhibitor includes a compound of general formula (I): wherein the meanings of the variables are explained in the specification, or a stereoisomeric form or a mixture of stereoisomeric forms, or pharmaceutically acceptable salts thereof. A pharmaceutical composition can include compounds of the invention, which can be used in a method for inhibiting TLR9 activity in vitro or in vivo. The method can be performed by administering the compound to a subject to inhibit TLR9 activity, which can be used to treat a disease or disorder associated with TLR9.

Abstract: A TNIK and/or MAP4K4 kinase inhibitor can include: Formula A, derivative, prodrug, salt, stereoisomer, tautomer polymorph, or solvate thereof, or having chirality at any chiral center, wherein: ring 1 is an aromatic ring with or without hetero atoms; ring 2 is a hetero aromatic ring; ring 3 includes at least one hetero aromatic ring and optionally at least one cycloaliphatic ring fused with the at least one hetero aromatic ring; ring 4 is an aromatic ring with or without hetero atoms; Y is a bond or a linker; Y1 is a linker; each n is independently 0, 1, or 2; each o is independently 0, 1, 2, 3, 4, or 5; each R1, R6, R11, and R12 is independently a substituent; and RA is a ring structure, straight aliphatics, or branched aliphatics, which can be substituted or unsubstituted, any with or without hetero atoms.

Abstract: Described herein are PHD inhibitors and pharmaceutical compositions comprising said inhibitors. The subject compounds and compositions are useful for the treatment of anemia.

Abstract: A method of inhibiting TNIK and/or MAP4K4 kinase can include: contacting the kinase with a compound of Formula A, wherein: ring 1 is an aromatic ring with or without hetero atoms; ring 2 is a hetero aromatic ring; ring 3 includes at least one hetero aromatic ring and optionally at least one cycloaliphatic ring fused with the at least one hetero aromatic ring; ring 4 is an aromatic ring with or without hetero atoms; Y is a bond or a linker; Y1 is a linker; each n is independently 0, 1, or 2; each o is independently 0, 1, 2, 3, 4, or 5; each R1, R6, R11, and R12 is independently a substituent; and RA is a ring structure, straight aliphatics, or branched aliphatics, which can be substituted or unsubstituted, any with or without hetero atoms.

Abstract: The disclosure provides for small molecules inhibitory compounds of ubiquitin specific protease 1 (USP1) and compositions comprising the same. The disclosure further provides methods for targeting ubiquitin specific protease 1 (USP1) and methods of treating diseases or disorders related to USP1, such as cancer.

Abstract: Described herein are PHD inhibitors and pharmaceutical compositions comprising said inhibitors. The subject compounds and compositions are useful for the treatment of inflammatory bowel disease.

Abstract: Provided herein are compounds, pharmaceutical compositions, and methods for treating a SARS-CoV-2 infection.

Abstract: A method is provided for generating new objects having given properties, such as a specific bioactivity (e.g., binding with a specific protein). In some aspects, the method can include: (a) receiving objects (e.g., physical structures) and their properties (e.g., chemical properties, bioactivity properties, etc.) from a dataset; (b) providing the objects and their properties to a machine learning platform, wherein the machine learning platform outputs a trained model; and (c) the machine learning platform takes the trained model and a set of properties and outputs new objects with desired properties. The new objects are different from the received objects. In some aspects, the objects are molecular structures, such as potential active agents, such as small molecule drugs, biological agents, nucleic acids, proteins, antibodies, or other active agents with a desired or defined bioactivity (e.g., binding a specific protein, preferentially over other proteins).

Abstract: The proposed model is a Variational Autoencoder having a learnable prior that is parametrized with a Tensor Train (VAE-TTLP). The VAE-TTLP can be used to generate new objects, such as molecules, that have specific properties and that can have specific biological activity (when a molecule). The VAE-TTLP can be trained in a way with the Tensor Train so that the provided data may omit one or more properties of the object, and still result in an object with a desired property.

Abstract: The disclosure provides TNIK and/or MAP4K4 kinases inhibitors for the treatment of disease. In one aspect, disclosed herein are kinase inhibitors having a structure of Formula (A), (A*), (I), (IIA), or (IIB). Further described herein are pharmaceutical composition comprising these compounds and methods of using these compounds. In one aspect, disclosed herein are methods of treating a disease or condition by administering the kinases inhibitors described herein.

Abstract: The disclosure provides TNIK and/or MAP4K4 kinases inhibitors for the treatment of disease. In one aspect, disclosed herein are kinase inhibitors having a structure of Formula (A), (A*), (I), (IIA), or (IIB). Further described herein are pharmaceutical composition comprising these compounds and methods of using these compounds. In one aspect, disclosed herein are methods of treating a disease or condition by administering the kinases inhibitors described herein.

Abstract: A DDR1 inhibitor compound can have a structure of Formula A, derivative thereof, prodrug thereof, salt thereof, stereoisomer thereof, tautomer thereof, polymorph thereof, or solvate thereof, or having any chirality at any chiral center, ring A is a ring structure; ring B is a ring structure; the X1, X2, X3, X4, and X5 are each independently a carbon or a hetero atom with or without a substituent; the Y is a linker; and each R1, R2, R3, R5, and R6 is independently a substituent; and each n is an integer, such as from 0 to the maximum number of allowed substituents on the linker or ring, wherein R5 and/or R6 is optionally nothing.

Abstract: A method for generating an object includes: providing a dataset having object data and condition data; processing the object data to obtain latent object data and latent object-condition data; processing the condition data to obtain latent condition data and latent condition-object data; processing the latent object data and the latent object-condition data to obtain generated object data; processing the latent condition data and latent condition-object data to obtain generated condition data; comparing the latent object-condition data to the latent condition-object data to determine a difference; processing the latent object data and latent condition data and one of the latent object-condition data or latent condition-object data to obtain a discriminator value; and selecting a selected object based on the generated object data.

Abstract: A method of treating senescence in a subject can include applying a senoremediation drug treatment protocol to the subject in order to rescue one or more first cells in the subject, wherein the senoremediation drug treatment protocol is derived from a computational transcriptome analysis of the tissue or organ of the subject. The method can include applying a senolytic drug treatment protocol to the subject in order to remove one or more second cells in the subject. The method can include introducing stem cells into a tissue and/or organ of the subject in order to rejuvenate one or more tissue cells in the tissue and/or one or more organ cells in the organ. The method can include carrying out a reinforcement step that includes one or more actions that prevent further senescence or degradation of the tissue or organ.

Abstract: A method for inhibiting TLR9 includes contacting the TLR9 with compound of general formula (I): wherein the meanings of the variables are explained in the specification, or a stereoisomeric form or a mixture of stereoisomeric forms, or pharmaceutically acceptable salts thereof. A pharmaceutical composition can include compounds of the invention, which can be used in a method for inhibiting TLR9 activity in vitro or in vivo. The method can be performed by administering the compound to a subject to inhibit TLR9 activity, which can be used to treat a disease or disorder associated with TLR9.

Abstract: A method for inhibiting TLR7 and/or TLR8 receptors includes contacting the receptor with compound of general formula (I): wherein the meanings of the variables are explained in the specification, or a stereoisomeric form or a mixture of stereoisomeric forms, or pharmaceutically acceptable salts thereof. A pharmaceutical composition can include compounds of the invention, which can be used in a method for inhibiting TLR7 receptors and/or TLR8 receptors. The method can be performed by administering the compound to a subject to inhibit TLR7, TLR8, or TLR7/8 activity, which can be used to treat a disease or disorder associated with the receptors.

Abstract: The present invention provides gero-protective pharmaceutical compositions and methods, the compositions being adapted to enhance at least one of cell survival and cell metabolism in a mammalian subject, the pharmaceutical compositions include at least two of Withaferin a or its structural analogs, coumestrol, ginsenoside, quinidine, silymarin, licochalcone a, lipoic acid and apigenin, in a pharmaceutically effective amount.