DYRK Inhibitor

Multi-kinase-IN-14 is an orally active and blood-brain barrier-permeable multi-kinase inhibitor. Multi-kinase-IN-14 reduces the excessive phosphorylation of α-synuclein by inhibiting four kinases (ABL1, DYRK1A, GSK3β, and LRRK2) and stabilizing microtubules. Multi-kinase-IN-14 is applicable for research on neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease.

Licocoumarone is an active component derived from licorice. Licocoumarone has an IC₅₀ of 12.56 μM and a K_d of 14.90 μM against human DYRK1A. Licocoumarone inhibits NF-κB activation by blocking IκBα degradation and p65 phosphorylation, interferes with MAPK activation via inhibiting phosphorylation, and downregulates the expression of iNOS. Licocoumarone inhibits LPS-induced expression of IL-1β, IL-6 and IL-10; it induces apoptosis of pancreatic cancer cells apoptosis and acts as a neuraminidase inhibitor (IC₅₀ = 27.8 μM). Licocoumarone exhibits anti-inflammatory and antimicrobial activities, with antibacterial activity against Listeria and antifungal activity against Candida parapsilosis. Licocoumarone can be used in studies related to immune and inflammatory diseases, pancreatic cancer, and specific bacterial and fungal infections.

Norharmine is a Harmine analogue and an alkaloid. Norharmine is the inhibitors of MAO-A and DYRK1A. Norharmine has weak inhibitory activity against MAO-A and certain inhibitory activity against DYRK1A.

tBID (Standard) is the analytical standard of tBID (HY-100464). This product is intended for research and analytical applications. tBID is a selective inhibitor of homeodomain-interacting protein kinase 2 (HIPK2) with an IC50 of 0.33 μM.

LDN-209929 dihydrochloride (Standard) is the analytical standard of LDN-209929 (dihydrochloride) (HY-110320). This product is intended for research and analytical applications. LDN-209929 dihydrochloride is a potent and selective haspin K_inase inhibitor (IC₅₀=55 nM) with180-fold selectivity verses DYRK2 (IC₅₀=9.9 μM). LDN-209929 is a optimized analogue of LDN-192960 (HY-13455).

Dyrk1A-IN-11 (compound 166) is a potent dual-specificity tyrosine phosphorylation- regulated 1A (DYRK1A) inhibitor with an EC₅₀ value of 0.0021 µM. Dyrk1A-IN-11 inhibits the Phospho-Tau (Thr212) with an EC₅₀ value of 0.0361 µM.

RD0448 is a potent inhibitor of DYRK1A, DYRK1B, and DYRK2. RD0448 selectively targets the non-native (folded intermediate) state of DYRK1A and DYRK1B. The binding site of RD0448 is hidden in the native state of DYRK1A and DYRK1B, and as a stabilizing binder, it binds tightly to both DYRK1A and DYRK1B, forming a stable complex with slow dissociation kinetics. In contrast, RD0448 targets the native state of DYRK2 without selectivity between its native and non-native states, acting as a weak binder with weaker binding affinity to DYRK2 and forming a rapidly dissociating complex.

INDY (Standard) is the analytical standard of INDY (HY-108476). This product is intended for research and analytical applications. INDY is a potent and ATP-competitive Dyrk1A and Dyrk1B inhibitor with IC₅₀s of 0.24 μM and 0.23 μM, respectively. INDY binds in the ATP pocket of the enzyme and has a K_i value of 0.18 μM for Dyrk1A. INDY sharply reduces the self-renewal capacity of normal and tumorigenic cells in primary Glioblastoma (GBM) cell lines and neural progenitor cells.

GSK-626616 (Standard) is the analytical standard of GSK-626616 (HY-105309). This product is intended for research and analytical applications. GSK-626616 is a potent, orally bioavailable inhibitor of DYRK3 (IC₅₀=0.7 nM). GSK-626616 inhibits other members of the DYRK family (e.g., DYRK1A and DYRK2) with similar potency, which is a potential therapy for the treatment of anemia.

Aristolactam BIII is a potent DYRK1A inhibitor and inhibits the kinase activity of DYRK1A in vitro (IC₅₀= 9.67 nM. Aristolactam BIII rescues the proliferative defects of DYRK1A transgenic (TG) mouse-derived fibroblasts and neurological and phenotypic defects of DS-like Drosophila models.

Harmine Hydrochloride (Telepathine Hydrochloride) is a natural DYRK inhibitor with anticancer and anti-inflammatory activities. Harmine has a high affinity of 5-HT2A serotonin receptor, with an Ki of 397 nM.

DYRKi is an inhibitor of DYRK1 and DYRK1B with IC₅₀ values of 3.7 µM and 90 nM, respectively, which is used as a potent antagonist of Hh/Gli signaling. DYRKi impairs SMO-dependent and SMO-independent oncogenic GLI activity in human medulloblastoma cells. DYRKi is promising for research of HH/GLI-associated cancers.

Dyrk1A-IN-9 (Compound L9) is a moderately active DYRK1A inhibitor (IC₅₀: 1.67 μM). L9 shows neuroprotective activity by regulating the expression of Aβ and phosphorylation of Tau protein. Dyrk1A-IN-9 can be used for research of Alzheimer's disease.

ProINDY, a prodrug of INDY (HY-108476), is a DYRK1A and DYRK1B inhibitor. ProINDY effectively recovers Xenopus embryos from head malformation induced by Dyrk1A overexpression.

Dyrk1A-IN-6 (compound 7cc) is an EGCG-like non-competitive inhibitor of DYRK1A. Dyrk1A-IN-6 can be used to alleviate cognitive defects in Down syndrome models.

Dyrk1A-IN-2 (Compound 63) is a DYRK1A inhibitor with an EC₅₀ of 37 nM. Dyrk1A-IN-2 exhibits highly potent human β-cell replication-promoting activity and low cytotoxicity.

Dyrk1A-IN-12 (compound S43) is a Dyrk (Dual specificity tyrosine phosphorylation regulated kinase 1A inhibitor. Dyrk1A-IN-12 inhibits Dyrk1A with a IC₅₀ of 95 nM. Dyrk1A-IN-12 shows anti-EV-A71 activity with an EC₅₀ of 4.4 μM, CC₅₀ of 12.8 μM and SI of 2.9. Dyrk1A-IN-12 shows potent inhibition against herpes simplex virus (HSV).