| Identification | Back Directory | [Name]
Benzenesulfonamide, N-[1,2-dihydro-1-methyl-4-(4-methyl-1H-imidazol-1-yl)-2-oxopyrrolo[4,3,2-de]quinolin-6-yl]-2-methoxy- | [CAS]
2543545-44-2 | [Synonyms]
LT052
Benzenesulfonamide, N-[1,2-dihydro-1-methyl-4-(4-methyl-1H-imidazol-1-yl)-2-oxopyrrolo[4,3,2-de]quinolin-6-yl]-2-methoxy- | [Molecular Formula]
C22H19N5O4S | [MOL File]
2543545-44-2.mol | [Molecular Weight]
449.48 |
| Chemical Properties | Back Directory | [Boiling point ]
759.4±70.0 °C(Predicted) | [density ]
1.49±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 10.42 mg/mL (23.18 mM; Need ultrasonic) | [form ]
Solid | [pka]
6.87±0.20(Predicted) | [color ]
Yellow to orange |
| Hazard Information | Back Directory | [Uses]
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]. | [Biological Activity]
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]. | [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[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]. | Animal Model: | Male Adult Sprague-Dawley rats (250-280 g) (acute gouty arthritis animal models)[1] | | Dosage: | 1 mg/kg | | Administration: | Intra-articular injection | | Result: | Restored the joint circumference to normal level. |
| [IC 50]
BRD4 BD1: 87.7 nM (IC50); BRD3 BD1: 246.3 nM (IC50); BRDT BD1: 357.1 nM (IC50); BRPF1b: 567.5 nM (IC50) | [References]
[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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