To assess BTK degradation in Ramos human Burkitt’s lymphoma B cells. Results showed that BTK degradation is observed within 1 hour and is complete within 2 hours.
Jeff Mihalic etal.
TMD8 ABC DLBCL cells
50 nM
6 hours
To assess the selectivity of NX-5948 for BTK in TMD8 ABC DLBCL cells. Results showed that NX-5948 is selective for BTK.
Jeff Mihalic etal.
TMD8 cells
< 10 nM (EC50)
72 hours
To assess the impact of NX-5948 on cell viability in TMD8 cells. Results showed that NX-5948 impairs viability with an EC50 of < 10 nM.",
Daniel W Robbins etal.
Lymphoma cell lines
< 1 nM (DC50)
To assess the degradation of BTK in lymphoma cell lines. Results showed that NX-5948 catalyzes the degradation of 50% of cellular BTK (DC 50) at < 1 nM concentrations.
Daniel W Robbins etal.
PBMCs
< 1 nM (DC50)
To assess the degradation of BTK in peripheral blood mononuclear cells (PBMCs). Results showed that NX-5948 catalyzes the degradation of 50% of cellular BTK (DC 50) at < 1 nM concentrations.
Daniel W Robbins etal.
Primary human B cells
0.0001, 0.001, 0.01, 0.1, 1, 10, 100, 1000 nM
To assess BTK degradation in primary human B cells. Results showed that NX-5948 achieved a DC50 of 0.034 nM.
Jeff Mihalic etal.
PBMCs
Sub-nanomolar concentrations
To assess the degradation of BTK and inhibition of BCR signaling in human PBMCs. Results showed that NX-5948 degrades BTK at sub-nanomolar concentrations and inhibits BCR signaling.
D.Robbins etal.
NX-5948 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
CD-1 mice and cynomolgus monkeys
Collagen-induced arthritis (CIA) model
Oral
10 mg/kg
Single dose
To assess the degradation of BTK and anti-inflammatory activity in a CIA model. Results showed that NX-5948 resolved symptoms of arthritis, reduced arthritis clinical score, anti-type II collagen titer, and serum levels of IL-6.
D.Robbins etal.
BALB/c mice
TMD8 tumor model
Oral
3, 10, 30 mg/kg
Daily, 26 days
To assess the efficacy of NX-5948 in a TMD8 tumor model. Results showed that NX-5948 significantly inhibited tumor growth at doses of 3, 10, and 30 mg/kg.
Jeff Mihalic etal.
Mice
TMD8 xenograft model
Oral
Daily
To assess the efficacy of NX-5948 in a TMD8 xenograft model. Results showed that daily oral administration of NX-5948 resulted in superior tumor growth inhibition (TGI) as compared to ibrutinib.
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