DGK Inhibitor

CU-3 is a DGKα inhibitor with an IC₅₀ of 0.6 μM. CU-3 competitively reduces DGKα’s affinity for ATP via binding to the enzyme’s catalytic region. CU-3 induces apoptosis in cancer cells. CU-3 promotes T-cell activation and enhances IL-2 production. CU-3 can be used for the research of hepatocellular carcinoma and cervical cancer.

DGK-IN-11 (Compound 1) is a diacylglycerol kinase (DGK) inhibitor. DGK-IN-11 exhibits inhibitory activity against DGKα and DGKγ. DGK-IN-11 regulates intracellular diacylglycerol levels and enhances T cell activation, cytokine production, and proliferation. DGK-IN-11 can be used for the study of cancer.

DGKα-IN-10 is an orally active and potent DGKα inhibitor with an IC₅₀ of 0.27 nM. DGKα-IN-10 can induce IL-2 release and T cells proliferation. DGKα-IN-10 can be used for the research of cancer, such as colon cancer.

DGKα-IN-8 (Example 51) is a DGKα inhibitor (IC₅₀=22.491 nM; EC₅₀=0.256 nM). DGKα-IN-8 can be used to study cancer, including solid tumors, and viral infections, such as HIV or hepatitis B virus infection.

DGKα-IN-9 is a diacylglycerol kinase alpha (DGKα) inhibitor. DGKα-IN-9 demonstrates a tumor growth inhibition in MC38 or or CT26 mouse tumor model. DGKα-IN-9 can be used for the study of cancer.

DGK-IN-8 (Example 34) is a DGK inhibitor, with IC₅₀ of ≤ 20 nM for DGKα and ζ. DGK-IN-8 can be used for cancer research.

DGKα-IN-4 (example 432) is a DGKα inhibitor with the IC₅₀ of 0.1 nM, extracted from patent WO2021105117. DGKα-IN-2 significantly enhances the anti-tumor effect of anti-PD-1 by increasing the proliferation and function of T cells. DGKα-IN-3 has the potential for cancer and immunology study.

DGKζ-IN-3 is a DGK-zeta-inhibitor. DGKζ-IN-3 is used in liquid and solid cancer and other diacylglycerol kinase zeta (DGK-ζ) regulation of diseases.

DGKζ-IN-10 (compound 349) is a DGKζ inhibitor, with an IC₅₀ ≤200 nM.

DGKα-IN-3 (example 25) is a DGKα inhibitor with the IC₅₀ of 283 nM, extracted from patent WO2021105115. DGKα-IN-2 significantly enhances the anti-tumor effect of anti-PD-1 by increasing the proliferation and function of T cells. DGKα-IN-2 has the potential for cancer and immunology study.

DGKα/ζ-IN-2 is a potent, orally active and selective dual DGKα/ζ inhibitor with IC₅₀ values of 23 nM (DGKα) and 1.2 nM (DGKζ). DGKα/ζ-IN-2 exhibits selectivity over other DGK isoforms, such as DGKβ and DGKγ. DGKα/ζ-IN-2 shows robust and dose-dependent immune activation in the presence of antigen presentation in an OT-1 murine model. DGKα/ζ-IN-2 can be used for antitumor immunity.

DGKζ-IN-7 (compound 97) is an oral active DGKζ inhibitor with the IC₅₀ of 33.4 nM. DGKζ-IN-6 inhibits the secretion of IL-2 and can be used for study of cancer and autoimmune diseases.

DGKζ-IN-5 is a DGKζ inhibitor (WO2023125681A1; compound A27a).

DGKα-IN-6 is a DGKα inhibitor with the IC₅₀ of 1.377 nM, extracted from patent WO2022271650 (compound 143). DGKα-IN-6 has the potential for cancer study.

DGK-IN-13 is a DGK inhibitor. DGK-IN-13 can be used for the research of cancer.

Cochlioquinone A is a ATP-competive diacylglycerol kinase inhibitor (K_i: 3.1 μM). Cochlioquinone A can be isolated from Drechslera sacchari.

DGKα/ζ-IN-1 (Compound II) is a DGK target inhibitor. DGKα/ζ-IN-1 can enhance the function of T cells, and has a synergistic effect with PD-1, which has therapeutic effects IN both immune and tumor.

DGK-IN-12 is a DGK inhibitor. DGK-IN-12 can be used for the research of cancer.

DGKζ-IN-9 (compound 73) is a DGKζ inhibitor, with an IC₅₀ ≤200 nM.

JNJ-3790339, a Ritanserin (HY-10791) analog, is a potent and selective diacylglycerol kinase (DGKα) inhibitor with an IC₅₀ of 9.6 μM. JNJ-3790339 has induction of toxicity in malignant cells, and improves ability to upregulate T cell activation.