DGK Inhibitor

BAY 2965501 is a potent and selective diacylglycerol kinase zeta (DGKζ) inhibitor. BAY 2965501 induces pERK activation. BAY 2965501 can be used for the research of cancer.

BMS-502 (Compound 22) is a potent dual inhibitor of diacylglycerol kinase (DGK) α and ζ with IC₅₀ of 4.6 nM and 2.1 nM. BMS-502 enhanced T cell immune responses in mice. BMS-502 can be used in tumor immunity related research.

BMS-684 is a selective DGKα inhibitor with an IC₅₀ of 15 nM. BMS-684 inhibits DGKα kinase activity with >100-fold selectivity over the related DGK type I family members DGKβ and DGKγ. BMS-684 does not inhibit any of the other seven DGK isozymes.

BMS-986408 is an orally active inhibitor of DGKα and DGKζ, with IC₅₀ values of 0.0003 μM and 0.002 μM, respectively. BMS-986408 activates intratumoral T cell responses, enhances the priming and expansion of tumor-reactive T cells in tumor-draining lymph nodes, and functions as an immunostimulant. BMS-986408 can be used in the research of tumors.

Alcudacigib (ASP1570; DGKζ-IN-1) TFA is an orally active diacylglycerol kinase ζ (DGKζ) inhibitor, with an IC₅₀ of 4.7 nM against human DGKζ and an IC₅₀ of 3.0 nM against mouse DGKζ. Alcudacigib TFA selectively inhibits the kinase activity of DGKζ and induces proteasome-dependent degradation of DGKζ protein. Alcudacigib TFA enhances the anti-tumor functions of T cells and NK cells. Alcudacigib TFA can be used for the research of advanced/metastatic solid tumors.

DGK-IN-10 (example 61) is a DGK inhibitor with IC₅₀ values of ≤ 10 nM for both DGKα and DGKζ. DGK-IN-10 can be used for the research of diseases including cancer.

INCB191358 is a selective and orally active inhibitor of diacylglycerol kinase α/ζ/ι (DGKα/ζ/ι ) with IC₅₀ values of 0.12, 0.36 and 0.36 nM. INCB191358 induces antigen-dependent T-cell activation, induces IL-2 production and enhances antitumor efficacy in combination with PD-1 blockade. INCB191358 can be used for the research of cancer, such as colon carcinoma.

(5Z,2E)-CU-3 is an isomer of CU-3 (HY-121638). 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.

Dioctanoylglycol (Ethylene glycol dicaprylate), a diacylglycerol analog, is a diacylglycerol kinase (DGK) inhibitor (K_i of 58 μM).

BMS-332 is a dual DGKα/ζ lipid kinase inhibitor, with IC₅₀s of 5 and 1 nM against DGKα and DGKζ, respectively. BMS-332 enhances the antigen-specific T cell response. BMS-332 reduces the viral load in the liver and spleen when combined with anti-PD-1 in chronic infection models. BMS-332 can be used for the study of T cell immune checkpoint strategy.

(S)-BAY 2965501 is the left-handed isomer of BAY 2965501 (HY-153343). BAY 2965501 is a potent and selective diacylglycerol kinase zeta (DGKζ) inhibitor. BAY 2965501 induces pERK activation. BAY 2965501 can be used for the research of cancer.

DGK-IN-1 is a DGK inhibitor (DGKa/DGKz IC₅₀: 0.65/0.25 μM). DGK-IN-1 is a T cell activator that can be used in cancer and viral infection research.

DGKα-IN-2 (example 48) is a DGKα inhibitor with the IC₅₀ of 0.9 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.

AMB639752 is a potent DGKα inhibitor. AMB639752 restores restimulation induced cell death (RICD) in SAP deficient lymphocytes by inhibiting DGKα in intact cells. AMB639752 can be used for X-linked lymphoproliferative disease 1(XLP-1) research.

Momordicine I is a cucurbitane-type triterpenoids. Momordicine I suppresses glioma growth by promoting apoptosis and impairing mitochondrial oxidative phosphorylation. Momordicine I inhibits glycolysis, lipid metabolism, induces autophagy in HNC cells to suppress head and neck cancer growth. Momordicine I alleviates isoproterenol-induced cardiomyocyte hypertrophy through suppression of PLA2G6 and DGK-ζ. Momordicine I exerts its cardiovascular benefits by upregulating nitric oxide, inhibiting the activity of angiotensin-converting enzyme (ACE), activating the PI3K/Akt pathway, reducing oxidative stress and inflammation. Momordicine I inhibits AKT1, IL-6, and SRC, suggesting its potential application in type 2 diabetes.

DGKζ-IN-4 is a DGK-zeta inhibitor. DGKζ-IN-4 can be used as an active component of pharmaceutical compositions. DGKζ-IN-4 is used to treat cancers associated with immune cell activation or cancers resistant to anti-PD-1 antibody/anti-PD-11 antibody research.

Alcudacigib (ASP1570; DGKζ-IN-1) is an orally active diacylglycerol kinase ζ (DGKζ) inhibitor, with an IC₅₀ of 4.7 nM against human DGKζ and an IC₅₀ of 3.0 nM against mouse DGKζ. Alcudacigib selectively inhibits the kinase activity of DGKζ and induces proteasome-dependent degradation of DGKζ protein. Alcudacigib enhances the anti-tumor functions of T cells and NK cells. Alcudacigib can be used for the research of advanced/metastatic solid tumors.

BMS-496 is adualDGKα/ζlipid kinase inhibitor, with theIC₅₀of 0.09 (DGKα) and 0.006 μM (DGKζ).

DGKα-IN-9 (example 298) is an inhibitor of DGKα.

(1R)-BMS-986408 is an orally active dual DGK α/ζ inhibitor that restores T cell-mediated anti-tumor immunity by enhancing T cell signaling.