LT052 is a highly selective BET BD1 inhibitor with an IC 50 of 87.7 nM. LT052 exhibits nanomolar BRD4 BD1 potency and 138-fold selectivity over BRD4 BD2 (IC 50 =12.130 μM). LT052 has anti-inflammatory activity and can be used for acute gout arthritis research
In Vitro
LT052 (1 μM) inhibits NF-κB transcriptional activity in HUVECs cells and inhibit nitric oxide (NO) production (inhibition rate: 101.89%) in RAW264.7 cells. In the evaluation of in vitro inflammatory activity, LT052 maintains comparable or better anti-inflammatory activity than the pan-BET inhibitor (JQ1) compared to the protein weak activity. LT052 displays the highinhibitory activity against BRD4(1) (IC 50 : 87.7±4.9 nM), BRD3(1) (IC 50 : 246.3±20.2 nM), and BRDT(1) (IC 50 : 357.1±8.3 nM). LT052 also has inhibitory activities against BRPF1b (IC 50 : 567.5±16.9 nM). Additionlly, LT052 shows a 238-fold selectivity toward BD1 over BD2 with K d of 105 nM and >25 μM for BD1 and BD2, respectively. LT052 (1 μM; 1 hour) inhibits MSU-induced pyroptosis of THP-1 cells through BRD4/NF-κB/NLRP3 signaling pathways. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
LT052 (1 mg/kg; intra-articular) suppresses synovial hyperplasia as well as severe neutrophil infiltration, and has a good therapeutic effect on MSU-induced acute gouty arthritis . LT052 suppresses pyroptosis of macrophages in rat synovial tissues through regulating BRD4/NF-κB/NLRP3 signaling pathway . LT052 has a high clearance rate in the range of 93.517 µL/min/mg proteins to 146.685 µL/min/mg proteins in liver microsomes of multiple species (human, monkey, dog, rat). Overall, LT052 exhibits moderately stable levels of in vitro liver microsomal metabolism . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male Adult Sprague-Dawley rats (250-280 g) (acute gouty arthritis animal models) Dosage: 1 mg/kg Administration: Intra-articular injection Result: Restored the joint circumference to normal level.
