Gusacitinib Chemical Properties

Density 

1.47±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMSO:100.0(Max Conc. mg/mL);217.14(Max Conc. mM)

form 

A crystalline solid

pka

9.17±0.20(Predicted)

color 

Light yellow to yellow

InChI

InChI=1S/C24H28N8O2/c25-10-5-16-6-11-32(12-7-16)24-28-20-15-26-30-23(34)21(20)22(29-24)27-17-1-3-18(4-2-17)31-13-8-19(33)9-14-31/h1-4,15-16,19,33H,5-9,11-14H2,(H,30,34)(H,27,28,29)

InChIKey

NLFLXLJXEIUQDL-UHFFFAOYSA-N

SMILES

N1(C2=NC(NC3=CC=C(N4CCC(O)CC4)C=C3)=C3C(=O)NN=CC3=N2)CCC(CC#N)CC1

Gusacitinib Usage And Synthesis

Description

Gusacitinib is an orally bioavailable, potent dual inhibitor of Janus kinases (JAK 1, 2, 3, and TYK2) and spleen tyrosine kinase (SYK) with 50% inhibitory concentrations (IC50 values) of 5 to 46 nM in biochemical assays. Gusacitinib targets both Th1 and Th2 inflammatory pathways, which are involved in CHE[1].

Uses

Gusacitinib is an oral Janus and Spleen tyrosine kinase inhibitor. It has been approved by the FDA for the treatment of moderate to severe chronic hand eczema. Gusacitinib is currently being used in clinical studies for the treatment of low-risk nodular basal cell carcinoma in adults.

brand name

ASN-002, EN-3351

Safety

During part A, 60 (61.9%) patients reported at least 1 AE (40 mg, 19 [57.6%]; 80 mg, 24 [75.0%]; and placebo, 17 [53.1%]). Most events were mild or moderate in severity. The most common events (≥10%) were upper respiratory infection, headache, and nausea with headache and gastrointestinal symptoms which were more prevalent with the 80 mg gusacitinib dose. The most common treatment-related events were headache and nausea. Three placebo patients were discontinued because of worsening of CHE. No serious AEs were considered to be related to the study treatment. Creatine phosphokinase elevations, known as drug class effect, were observed starting at week 4 (active treatment) and at week 20 (part B, placebo patients crossing over to 80 mg). No serious AEs were related to the study treatment. Five patients had creatine phosphokinase elevations reported as AEs. No thromboembolic or major cardiovascular events, malignancies, or deaths occurred[1].

in vitro

Gusacitinib shows anti-proliferative activity in a broad panel of human cancer cell lines, including DHL6, DHL4, OCI-LY10, H929, Pfeiffer, HT-1376, and Lovo, suggesting activity in both solid and hematological tumor types.

in vivo

Gusacitinib exhibits significant efficacy in inhibiting tumor growth (>95%) in a multiple myeloma (H929) xenograft model. Gusacitinib significantly delays the onset of hind limb paralysis in the human erythroleukemia (HEL) mouse model. Gusacitinib shows a favorable safety profile in rat and dog toxicology studies.

References

[1] Pablo A. Jimenez MD . “Oral spleen tyrosine kinase/Janus Kinase inhibitor gusacitinib for the treatment of chronic hand eczema: Results of a randomized phase 2 study.” Journal of the American Academy of Dermatology 89 2 (2023): Pages 235-242.