| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g | |||
| Other Sizes |
| Targets |
BDK (IC50 = 3.19 μM); Mcl-1 (IC50 = 59 μM)
Branched-chain α-ketoacid dehydrogenase kinase (BDK, also known as BCKDC kinase) and Mcl-1. BT2 is a BCKDC kinase (BDK) inhibitor with an IC₅₀ of 3.19 μM. It also functions as a selective Mcl-1 inhibitor with a Ki value of 59 μM. BT2 binding to BDK triggers helix movements in the N-terminal domain, leading to dissociation of BDK from the branched-chain α-ketoacid dehydrogenase complex (BCKDC). |
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| ln Vitro |
BT2 is a BCKDC kinase (BDK) inhibitor with an IC₅₀ of 3.19 μM and a selective Mcl-1 inhibitor with a Ki value of 59 μM. Binding of BT2 to BDK triggers helical movement of the N-terminal domain of the branched α-keto acid dehydrogenase complex (BCKDC), resulting in the dissociation of BDK from BCKDC.
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| ln Vivo |
BT2 (20 mg/kg/day; intraperitoneal injection; daily; for 7 days; C57BL/6J male mice) treatment significantly increases BCKDC activity in the heart (12.3-fold) when compared to vehicle-treated animals. At 3.6 and 3.8 times, respectively, less activation is obtained in the kidney and muscle. The decreased phosphorylation in the heart, muscle, and kidney following the long-term BT2 treatment is correlated with the -fold activation of BCKDC activity in the aforementioned tissues. Protein levels of BDK are lowered in the kidneys and heart after BT2 treatment[1].
BT2 treatment lowers BDK protein levels in the kidney and heart. Increased BCKDC activity in these tissues correlates with decreased phosphorylation after prolonged BT2 treatment in the heart, muscle, and kidney. BT2 (20 mg/kg/day; i.p.; daily; for 7 days; C57BL/6J male mice) significantly increases BCKDC activity in the heart (12.3-fold) compared to vehicle-treated animals; less activation is observed in muscle and kidney (3.6- and 3.8-fold, respectively). |
| Enzyme Assay |
In vitro enzyme assays for BT2 involve measuring its inhibition of BDK kinase activity or its binding to Mcl-1. BDK is incubated with ATP, a peptide substrate, and various concentrations of BT2. Kinase activity is measured by detecting phosphorylation of the substrate. IC₅₀ values (3.19 μM for BDK) are determined from concentration-response curves. Mcl-1 binding affinity (Ki = 59 μM) is assessed using binding assays.
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| Cell Assay |
Cellular assays for BT2 involve treating cells with the compound and measuring BDK activity, BCKDC activity, or Mcl-1 function. Cells are treated with various concentrations of BT2, and BDK activity is assessed by measuring phosphorylation of BCKDC. Mcl-1 inhibition is assessed by measuring effects on apoptosis or cell survival. The compound's ability to inhibit BDK and dissociate it from BCKDC is evaluated.
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| Animal Protocol |
In vivo animal studies for BT2 typically involve administration to mice to assess its effects on BDK activity and BCKDC function. BT2 (20 mg/kg/day; i.p.; daily; for 7 days; C57BL/6J male mice) significantly increases BCKDC activity in the heart (12.3-fold), with less activation in muscle and kidney (3.6- and 3.8-fold, respectively). BT2 treatment lowers BDK protein levels in the kidney and heart.
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| ADME/Pharmacokinetics |
BT2 has a molecular weight of 247.10 and a molecular formula of C₉H₄Cl₂O₂S. It has a density of 1.653 g/cm³. The compound should be stored at low temperature; powder at -20°C for up to 3 years and in solvent at -80°C for up to 1 year.
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| Toxicity/Toxicokinetics |
BT2 is a BCKDC kinase (BDK) inhibitor with an IC₅₀ of 3.19 μM and a selective Mcl-1 inhibitor with a Ki of 59 μM. It is well tolerated in mice at 20 mg/kg/day for 7 days.
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| References |
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| Additional Infomation |
BT2 is a small-molecule dual inhibitor targeting both branched-chain α-ketoacid dehydrogenase kinase (BDK, IC₅₀ = 3.19 μM) and the anti-apoptotic protein Mcl-1 (Ki = 59 μM). Binding of BT2 to BDK triggers helix movements in the N-terminal domain, leading to dissociation of BDK from the branched-chain α-ketoacid dehydrogenase complex (BCKDC). BT2 has been studied for its effects on BCKDC activity in the heart, muscle, and kidney.
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| Molecular Formula |
C9H4CL2O2S
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|---|---|
| Molecular Weight |
247.08
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| Exact Mass |
245.93
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| Elemental Analysis |
C, 43.75; H, 1.63; Cl, 28.69; O, 12.95; S, 12.98
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| CAS # |
34576-94-8
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| Related CAS # |
34576-94-8
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| PubChem CID |
739884
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| Appearance |
White to off-white solid powder
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| Density |
1.7±0.1 g/cm3
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| Boiling Point |
426.4±40.0 °C at 760 mmHg
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| Flash Point |
211.7±27.3 °C
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| Vapour Pressure |
0.0±1.1 mmHg at 25°C
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| Index of Refraction |
1.723
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| LogP |
4.65
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
14
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| Complexity |
249
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC2=C(C=C1Cl)SC(=C2Cl)C(=O)O
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| InChi Key |
AAHPIJMQJAZYTM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C9H4Cl2O2S/c10-4-1-2-5-6(3-4)14-8(7(5)11)9(12)13/h1-3H,(H,12,13)
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| Chemical Name |
3,6-dichloro-1-benzothiophene-2-carboxylic acid
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| Synonyms |
BT2; BT 2; BT-2
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 49~62.5 mg/mL(198.3~252.9 mM)
Ethanol: ~3 mg/mL (~12.1 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (8.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (8.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0473 mL | 20.2364 mL | 40.4727 mL | |
| 5 mM | 0.8095 mL | 4.0473 mL | 8.0945 mL | |
| 10 mM | 0.4047 mL | 2.0236 mL | 4.0473 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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