LT052

• CAT Number: I017380
• CAS Number: 2543545-44-2
• Molecular Formula: C22H19N5O4S
• Molecular Weight: 449.48
• Purity: ≥95%
• Synonyms: 2-methoxy-N-[2-methyl-6-(4-methylimidazol-1-yl)-3-oxo-2,7-diazatricyclo[6.3.1.04,12]dodeca-1(12),4,6,8,10-pentaen-9-yl]benzenesulfonamide
• InChI: InChI=1S/C22H19N5O4S/c1-13-11-27(12-23-13)19-10-14-20-16(26(2)22(14)28)9-8-15(21(20)24-19)25-32(29,30)18-7-5-4-6-17(18)31-3/h4-12,25H,1-3H3
• InChIKey: FSMTUHGXWGJNKK-UHFFFAOYSA-N
• SMILES: CC1=CN(C=N1)C2=NC3=C(C=CC4=C3C(=C2)C(=O)N4C)NS(=O)(=O)C5=CC=CC=C5OC

LT052 is a highly selective BET BD1 inhibitor with an IC50 of 87.7 nM. LT052 exhibits nanomolar BRD4 BD1 potency and 138-fold selectivity over BRD4 BD2 (IC50=12.130 μM). LT052 has anti-inflammatory activity and can be used for acute gout arthritis research[1].
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[1].LT052 displays the highinhibitory activity against BRD4(1) (IC50: 87.7±4.9 nM), BRD3(1) (IC50: 246.3±20.2 nM), and BRDT(1) (IC50: 357.1±8.3 nM). LT052 also has inhibitory activities against BRPF1b (IC50: 567.5±16.9 nM). Additionlly, LT052 shows a 238-fold selectivity toward BD1 over BD2 with Kd of 105 nM and >25 μM for BD1 and BD2, respectively[1].LT052 (1 μM; 1 hour) inhibits MSU-induced pyroptosis of THP-1 cells through BRD4/NF-κB/NLRP3 signaling pathways[1].
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[1].
LT052 suppresses pyroptosis of macrophages in rat synovial tissues through regulating BRD4/NF-κB/NLRP3 signaling pathway[1].
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[1].

Reference

[1]. Jiang F, et al. Discovery of Benzo[cd]indol-2(1H)-ones and Pyrrolo[4,3,2-de]quinolin-2(1H)-ones as Bromodomain and Extra-Terminal Domain (BET) Inhibitors with Selectivity for the First Bromodomain with Potential High Efficiency against Acute Gouty Arthritis. J Med Chem. 2019 Dec 26;62(24):11080-11107.
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