BT2 (3,6-dichlorobenzo[b]thiophene-2-carboxylic acid), an inhibitor of branched-chain ketoacid dehydrogenase kinase, promotes BCAA metabolism by enhancing BCKDH complex activity.

Aug 15, 2023 · The branched-chain ketoacid dehydrogenase kinase (BCKDK) inhibitor BT2 is often used in preclinical models to increase BCAA oxidation and restore steady-state BCAA and BCKA levels.

Nov 1, 2022 · BT2 is a potent inhibitor of BCKDK, thereby enhancing BCKDH activity. Administration of BT2 to mice reduces plasma BCAA and BCKA within 30 min of injection, without affecting the endogenous rate of appearance of BCAAs (Neinast et al., 2019).

Mar 15, 2021 · Branched-chain amino acids (BCAA) and their cognate α-ketoacids (BCKA) are elevated in an array of cardiometabolic diseases. Here we demonstrate that the major metabolic fate of uniformly- 13...

Aug 9, 2023 · High BCAA levels are indicators for future T2DM 20 and pancreatic cancer 21 development. HF and T2DM are also associated with a loss of BCAA catabolic machinery 10, 11, suggesting that BCKDH...

Aug 5, 2022 · Branched-chain amino acid (BCAA) catabolism has been considered to have an emerging role in the pathogenesis of metabolic disturbances in obesity and type 2 diabetes (T2D). Several...

Jul 5, 2019 · Cardiac BCAA oxidation in isolated working hearts was significantly enhanced by BT2, compared to vehicle, following either acute or chronic treatment. Treatment of TAC mice with BT2 significantly improved cardiac function in both sham and TAC mice (63.0 ± 1.8 and 56.9 ± 3.8% ejection fraction respectively).

Activating BCAA metabolism with BT2 could inhibit mTOR signaling, reduce PPF, and ameliorate thrombocythemia in BCAA-fed mice. Therefore, this study reveals a novel role of BCAAs in megakaryocyte differentiation and platelet production, suggesting that targeting BCAA-mediated p70S6K/mTOR signaling may be a potential strategy for the treatment ...

Jan 8, 2025 · By enhancing BCAA catabolism, BT2 reduced toxic BCAA accumulation, alleviated mTORC1 signaling, and improved mitochondrial function, collectively contributing to the preservation of kidney function and reduction of PT cellular injury.

Administration of branched-chain α-keto acid dehydrogenase (BCKD) kinase inhibitor BT2 has been shown to reduce cardiac BCAA levels and demonstrated positive effects on cardiac function in a preclinical setting.