BT2 is a BCKDC kinase (BDK) inhibitor (antagonist) with IC50 of 3.19 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. BT2 (compound 4) is also a potent and specific Mcl-1 inhibitor (antagonist) with Ki of 59 μM.

Physicochemical Properties

Molecular Formula	C9H4CL2O2S
Molecular Weight	247.08
Exact Mass	245.93
Elemental Analysis	C, 43.75; H, 1.63; Cl, 28.69; O, 12.95; S, 12.98
CAS #	34576-94-8
Related CAS #	34576-94-8
PubChem CID	739884
Appearance	White to off-white solid powder
Density	1.7±0.1 g/cm3
Boiling Point	426.4±40.0 °C at 760 mmHg
Flash Point	211.7±27.3 °C
Vapour Pressure	0.0±1.1 mmHg at 25°C
Index of Refraction	1.723
LogP	4.65
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	1
Heavy Atom Count	14
Complexity	249
Defined Atom Stereocenter Count	0
SMILES	C1=CC2=C(C=C1Cl)SC(=C2Cl)C(=O)O
InChi Key	AAHPIJMQJAZYTM-UHFFFAOYSA-N
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)
Chemical Name	3,6-dichloro-1-benzothiophene-2-carboxylic acid
Synonyms	BT2; BT 2; BT-2
HS Tariff Code	2934.99.9001
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)

Biological Activity

Targets	BDK (IC50 = 3.19 μM); Mcl-1 (IC50 = 59 μM)
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].
References	[1]. Benzothiophene carboxylate derivatives as novel allosteric inhibitors of branched-chain α-ketoacid dehydrogenase kinase. J Biol Chem. 2014 Jul 25;289(30):20583-93. [2]. Discovery of potent myeloid cell leukemia 1 (Mcl-1) inhibitors using fragment-based methods and structure-based design. J Med Chem. 2013 Jan 10;56(1):15-30.

Solubility Data

Solubility (In Vitro)

DMSO: 49~62.5 mg/mL(198.3~252.9 mM) Ethanol: ~3 mg/mL (~12.1 mM)

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.