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.

Product information

CAS Number: 2543545-44-2

Molecular Weight: 449.48

Formula: C22H19N5O4S

Chemical Name: 2-methoxy-N-[2-methyl-6-(4-methyl-1H-imidazol-1-yl)-3-oxo-2,7-diazatricyclo[6.3.1.0⁴,¹²]dodeca-1(11),4(12),5,7,9-pentaen-9-yl]benzene-1-sulfonamide

Smiles: CN1C2=CC=C(NS(=O)(=O)C3=CC=CC=C3OC)C3=NC(=CC(C1=O)=C32)N1C=NC(C)=C1

InChiKey: FSMTUHGXWGJNKK-UHFFFAOYSA-N

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

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 10.42 mg/mL (23.18 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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) (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. LT052 (1 μM; 1 hour) inhibits MSU-induced pyroptosis of THP-1 cells through BRD4/NF-κB/NLRP3 signaling pathways.

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.

Products are for research use only. Not for human use.