DAPK Inhibitor

TC-DAPK 6 is a potent, ATP-competitive, and highly selective DAPK inhibitor (IC₅₀=69 and 225 nM against DAPK1 and DAPK3, respectively, with 10 μM ATP).

HS38 is a potent, selective, and ATP-competitive inhibitor of death-associated protein kinase 1 (DAPK1) and zipper-interacting protein kinase (ZIPK, also called DAPK3), with K_ds of 300 nM and 280 nM, respectively. HS38 is also a PIM3 inhibitor with an IC₅₀ of 200 nM. HS38 can be used for the research of smooth muscle related disorders.

3MB-PP1, a bulky purine analog, is a Polo-like kinase 1 (Plk1) inhibitor. 3MB-PP1 blocks mitotic progression and cell division arise through target Plk1 in in cells expressing analog-sensitive Plk1 alleles. 3MB-PP1 specifically inhibits the activity of analog-sensitive Ssn3 (Cdk8). 3MB-PP1 inhibits Leu93 Mutant Zipper-interacting protein kinase (Leu93-ZIPK; IC₅₀=2 μM). 3MB-PP1 can be used for the research of hypha formation of Candida albicans and cell division.

DRAK2-IN-1, compound 16, is a potent, selective and ATP-competitive DRAK2 inhibitor with IC₅₀and K_ivalues of 3 nM and 0.26 nM, respectively. DRAK2-IN-1 also has inbitory effect on DRAK1 (IC₅₀=51 nM).

HS148 (compound 22) is a selective DAPK3 inhibitor with an K_i value of 119 nM.

GW296115 is a multi-target inhibitor with the following IC₅₀ values against its targets: 8.4 nM for BRSK2, 21 nM for BRSK1, 1.8 μM for PDGFRβ, 5.5 nM for STK17B/DRAK2, 28 nM for DRAK1, 20 nM for PHKG1, and 89 nM for DCAMKL3. GW296115 downregulates the phosphorylation of S317 site on ULK1 and S351 site on P62, which are AMPK substrates driven by BRSK2. GW296115 does not alter the phosphorylation level of AMPK at T172, reduces nutrient deprivation-mediated Autophagy and autophagosome formation, and enhances Apoptosis. GW296115 exhibits anticancer activity against triple-negative breast cancer. GW296115 is applicable for breast cancer-related research.

DAPK-IN-1 is a DAPK1 and DAPK3 inhibitor. DAPK-IN-1 is applicable to research related to cerebral infarction, myocardial infarction and renal failure.

DRAK2-IN-2 is a selective DRAK2 inhibitor with an IC₅₀ value of 198.5 nM. DRAK2-IN-2 inhibits DRAK2-mediated phosphorylation of ULK1 at the Ser56 site. DRAK2-IN-2 enhances insulin secretion, increases mitochondrial membrane potential, alleviates Palmitic acid (HY-N0830)-induced mitochondrial membrane potential damage and Apoptosis, and improves glucose tolerance in vivo. DRAK2-IN-2 can be used for the research of type 2 diabetes.

DIM-C-pPhCO2Me is a nuclear receptor 4A1 (NR4A1) antagonist. DIM-C-pPhCO2Me induces Apoptosis. DIM-C-pPhCO2Me decreases PAX3-FOXO1A, N-Myc, Rassf4, MyoD1, Grem1, and DAPK1 proteins. DIM-C-pPhCO2Me decreases expression of TXNDC5 and IDH1, induces markers of ER stress (CHOP, ATF4 and p-PERK). DIM-C-pPhCO2Me inhibits renal cell carcinoma, breast cancer. DIM-C-pPhCO2Me can also be used in rhabdomyosarcoma research.

SGC-STK17B-1, a chemical probe, is an ATP-competitive and selective STK17B (a member of DAPK family) inhibitor (IC₅₀: 34 nM, K_D: 5.6 nM).

TNIK-IN-3 is a potent, selective and orally active inhibitor of Traf2- and Nck-interacting protein kinase (TNIK), with an IC₅₀ of 0.026 μM. TNIK-IN-3 could also inhibit Flt4 (IC₅₀=0.030 μM), Flt1 (IC₅₀=0.191 μM) and DRAK1 (IC₅₀=0.411 μM). TNIK-IN-3 can be used for the research of colorectal cancer.

STK17A/B-IN-1 hydrochloride is an orally active, potent and selective STK17A/B inhibitor with an IC₅₀ value of 23 nM for STK17A. STK17A/B-IN-1 hydrochloride can be used in tumor research.

DAPK1-IN-1 (compound 10) is a death-associated protein kinase 1 (DAPK1) inhibitor with a K_d value of 0.63 μM. DAPK1-IN-1 can be used in Alzheimer’s disease research.

CK156, a chemical probe, is a highly selective death-associated protein kinase (DAPK) inhibitor with IC₅₀s of 182 nM,34 μM, and 39 μM in the DRAK1 NanoBRET assay for DRAK1, CK2a1, and CK2a2, respectively. CK156 can be used for the research of autoimmune and inflammatory diseases.

HS94 is a selective DAPK3 inhibitor. HS94 can be used for research of hypertension.

DAPK-IN-2 is a DAPK inhibitor. DAPK-IN-2 can be used for the research of cerebral infarction and ischemic diseases.

HS56 is an ATP-competitive dual Pim/DAPK3 inhibitor with K_i values of 0.26, 0.208, 2.94, and ＞100 μM for DAPK3, Pim-3, Pim-1, and Pim-2, respectively. HS56 inhibits LC20 phosphorylation and smooth muscle contraction. HS56 decreases blood pressure in spontaneously hypertensive mice. HS56 can be used in research of hypertension.

STK17A/B-IN-1 (compound 9) is an orally active, potent, and selective STK17A/B inhibitor with an IC₅₀ of 23 nM against STK17A. STK17A/B-IN-1 can be used for study of cancer.

DRAK1/2-IN-1 (compound 10e) is an active dual DRAK1 and DRAK2 inhibitor with K_d values of 1 μM and 6 μM, respectively.

UNC9750 is an inositol phosphate multikinase (IPMK) inhibitor with IC₅₀ values ​​of 31.6 and 374 nM for IPMK and IP6K2, respectively.. UNC9750 inhibits cellular accumulation of InsP₅, the direct product of IPMK kinase activity, while having no effect on either InsP6 or InsP₇ levels. UNC9750 has ≥ 75% inhibition of four kinases (DAPK1, DYRK1B, PDGFR, and KDR). UNC9750 can be used for the study of glioblastoma.