DF-003 

DF-003 is a selective, orally active, ATP-competitive, and brain-penetrant ALPK1 inhibitor. DF-003 potently inhibits human ALPK1 and ALPK1[T237M] with IC50s value of 1.5 nM and 16 nM. DF-003 exhibits more than 860-fold selectivity over the closest kinase. DF-003 inhibits TNF, CXCL10, or CXCL8 upregulation in HEK-293 cells. DF-003 can be used for the study of retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache (ROSAH) syndrome^[1].

DF-003 (1-50.8 pM, 60 h) dose-dependently inhibits ALPK1 kinase activity (IC_{50 = 1.5 nM)^[1].
DF-003 (20 μM-0.763 nM, 2 h) exhibits non-ALPK1 kinases inhibit activity for TAOK2/TAO1 (IC50=1.29 µM) , CAMK2g(IC50 = 3.10 µM), and CAMK1a (IC50 = 4.60 µM)^[1].
DF-003 (10-1000 nM, 1 h) potently suppresses DF-006 (HY-176507)-induced TIFAsome formation in HEK-293 cells, suggesting its intracellular inhibition of ALPK1^[1].
DF-003 (0.3-1000 nM, 6 h) exhibits the inhibition of DF-006-induced TNF (IC50 = 8 nM) and CXCL8 (IC50 = 6.5 nM) upregulation in THP-1 cells^[1].
DF-003 (1-50.8 pM, 60 h) inhibits UDP-mannose-stimulated ALPK1[T237M] in a dose-dependent manner (IC50 = 16 nM)^[1].
DF-003 (0.64-20 μM, 48 h) suppresses NF-κB reporter activity in the absence of exogenous stimulation in the ALPK1[T237M] OE HEK293 cells^[1].
DF-003 (0.64-20 μM, 30 h) dose-dependently inhibits cytokine upregulation in HEK-293 cells overexpressing ALPK1[T237M] and has no impact on the basal expression of TNF, CXCL10, or CXCL8 in cells overexpressing wild-type ALPK1 in HEK-293 cells^[1].
DF-003 (0.64-20 μM, 30 h) suppresses the enhanced secretion of CXCL8 from HEK-293 cells overexpressing ALPK1[T237M] (IC50 = 125 nM)^[1].}

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

DF-003 (3-5 mg/kg, oral gavage, once daily for 10 days) can effectively penetrate the blood-retinal barrier and the blood-brain barrier, inhibiting the multi-tissue inflammatory response caused by the ALPK1[T237M] mutation, including retinal microglial infiltration, astrocyte activation, and inflammatory cytokine expression in hALPK1[T237M]-KI C57BL/6N mice^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

486.96

C₂₄H₂₁ClF₂N₄OS

2765462-07-3

O=C(NC1=NC([C@@](C)(C#C)C2=CC=C(Cl)C=C2)=CS1)C(C(F)=C3)=C(F)C=C3N4CCNCC4

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Fan J,et al. Discovery of a selective alpha-kinase 1 inhibitor for the rare genetic disease ROSAH syndrome. Nat Commun. 202[1]5 Sep 9;16(1):8251.