Compounds, compositions and methods are provided for the inhibition of ENPP1. Aspects of the subject methods include contacting a sample with a ENPP1 inhibitor to inhibit cGAMP hydrolysis activity of ENPP1. In some cases, the ENPP1 inhibitor is cell impermeable. Also provided are compositions and methods for treating cancer. Aspects of the methods include administering to a subject a therapeutically effective amount of a ENPP1 inhibitor to treat the subject for cancer. In certain cases, the cancer is a solid tumor cancer. Also provided are methods of administering radiation therapy to a subject either before or after administering an ENPP1 inhibitor. The radiation therapy can be administered at a dosage and/or frequency effective to reduce radiation damage to the subject. In certain cases, the method is performed in combination with a chemotherapeutic agent, or a checkpoint inhibitor, or both.

Compounds, compositions and methods are provided for the inhibition of ENPP1. Aspects of the subject methods include contacting a sample with a ENPP1 inhibitor to inhibit cGAMP hydrolysis activity of ENPP1. In some cases, the ENPP1 inhibitor is cell impermeable. Also provided are compositions and methods for treating cancer. Aspects of the methods include administering to a subject a therapeutically effective amount of a ENPP1 inhibitor to treat the subject for cancer. In certain cases, the cancer is a solid tumor cancer. Also provided are methods of administering radiation therapy to a subject either before or after administering an ENPP1 inhibitor. The radiation therapy can be administered at a dosage and/or frequency effective to reduce radiation damage to the subject. In certain cases, the method is performed in combination with a chemotherapeutic agent, or a checkpoint inhibitor, or both.

β-Ketophosphonic acid according to general formula I: ##STR00001##
in which A=an aliphatic C.sub.1-C.sub.18 radical which can be interrupted by —O—, —S—, —CO—O— or —O—CO—C—; n=1, 2, 3 or 4; m=1 or 2; X=absent or a C.sub.1-C.sub.10 radical which can be interrupted by —O—, —S—, —CO—C—, —O—CO—NH— or —CO—NR.sup.1—, wherein R.sup.1 is H or C.sub.1-C.sub.7-alkyl; and PG=a group which can undergo free radical polymerization. The β-ketophosphonic acids are suitable in particular for the preparation of dental materials.

Acidic monomer according to Formula I:

##STR00001##

in which A is a linear or branched aliphatic C.sub.1-C.sub.18-hydrocarbon group, which can be interrupted by one or more —O—, —S—, —CO—O—, —O—CO—NH—, —HN—CO—NH— or —CO—NR.sup.1—; R.sup.1 is H or a C.sub.1-C.sub.6 alkyl group; X is absent or is a linear or branched aliphatic C.sub.1-C.sub.10 hydrocarbon group, which can be interrupted by one or more —O—, —S—, —CO—O—, —O—CO—NH—, —HN—CO—NH— or —CO—NR.sup.2—; R.sup.2 is H or a C.sub.1-C.sub.6 alkyl group; PG is a radically polymerizable group, preferably vinyl, allyl, CH.sub.2═CR.sup.3—CO—Y— or R.sup.4O—CO—C(═CH.sub.2)—CH.sub.2—Y—; Y═O or NR.sup.5 or is absent; R.sup.3 is H or CH.sub.3; R.sup.4 is H or a C.sub.1-C.sub.7 alkyl group; R.sup.5 is H or a C.sub.1-C.sub.7 alkyl group; n is 1, 2, 3 or 4; m=1 or 2; p=1, 2 or 3; and q=1, 2 or 3. The monomers are particularly suitable as components of dental material.

The invention provides novel pyrophosphate synthase inhibitors of formula I and formula II as well salts thereof; the invention also provides compositions comprising such inhibitors and methods for their use. ##STR00001##

[Problem]

To provide an alkenyl phosphorus compound.

[Means to Solve the Problem]

The method for manufacturing an alkenyl phosphorus compound according to the present invention is a method in which a specific phosphorus compound and a specific alkynyl compound are reacted in the presence of a transition metal complex and a Lewis acid, thereby giving an alkenyl phosphorus compound.

Compounds, compositions and methods are provided for the inhibition of ENPP1. Aspects of the subject methods include contacting a sample with a ENPP1 inhibitor to inhibit cGAMP hydrolysis activity of ENPP1. In some cases, the ENPP1 inhibitor is cell impermeable. Also provided are compositions and methods for treating cancer. Aspects of the methods include administering to a subject a therapeutically effective amount of a ENPP1 inhibitor to treat the subject for cancer. In certain cases, the cancer is a solid tumor cancer. Also provided are methods of administering radiation therapy to a subject either before or after administering an ENPP1 inhibitor. The radiation therapy can be administered at a dosage and/or frequency effective to reduce radiation damage to the subject. In certain cases, the method is performed in combination with a chemotherapeutic agent, or a checkpoint inhibitor, or both.

Hydrocarbyl tin complexs of alkynyl phosphonic acid with antitumor activity and their application are provided. Tests are conducted to evaluate activity, showing that the provided complexs have much stronger activity than cisplatin. The provided hydrocarbyl tin complexs can be potential candidate as a clinical antitumor drug.

Compounds, compositions and methods are provided for the inhibition of ENPP1. Aspects of the subject methods include contacting a sample with a ENPP1 inhibitor to inhibit cGAMP hydrolysis activity of ENPP1. In some cases, the ENPP1 inhibitor is cell impermeable. Also provided are compositions and methods for treating cancer. Aspects of the methods include administering to a subject a therapeutically effective amount of a ENPP1 inhibitor to treat the subject for cancer. In certain cases, the cancer is a solid tumor cancer. Also provided are methods of administering radiation therapy to a subject either before or after administering an ENPP1 inhibitor. The radiation therapy can be administered at a dosage and/or frequency effective to reduce radiation damage to the subject. In certain cases, the method is performed in combination with a chemotherapeutic agent, or a checkpoint inhibitor, or both.

Compounds, compositions and methods are provided for the inhibition of ENPP1. Aspects of the subject methods include contacting a sample with a ENPP1 inhibitor to inhibit cGAMP hydrolysis activity of ENPP1. In some cases, the ENPP1 inhibitor is cell impermeable. Also provided are compositions and methods for treating cancer. Aspects of the methods include administering to a subject a therapeutically effective amount of a ENPP1 inhibitor to treat the subject for cancer. In certain cases, the cancer is a solid tumor cancer. Also provided are methods of administering radiation therapy to a subject either before or after administering an ENPP1 inhibitor. The radiation therapy can be administered at a dosage and/or frequency effective to reduce radiation damage to the subject. In certain cases, the method is performed in combination with a chemotherapeutic agent, or a checkpoint inhibitor, or both.