| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
pIC50: 7.3 (BCATm), 6.6 (BCATc)[1]
Mitochondrial branched-chain aminotransferase (BCAT2/BCATm). BCAT-IN-2 is a potent and selective inhibitor of the mitochondrial isoform of branched-chain amino acid transaminase. It shows modest selectivity for BCATm over the cytosolic isoform BCATc (pIC50=6.6). By inhibiting BCAT2, it prevents the first and reversible step in BCAA catabolism, which is the transamination of BCAAs to their respective branched-chain α-keto acids. This leads to an increase in serum levels of BCAAs. |
|---|---|
| ln Vitro |
In differentiated primary human adipocytes, BCAT-IN-2 (Compound 61) inhibits BCATm with a pIC50 of 6.5 [1].
BCAT-IN-2 is a potent inhibitor of BCAT2 in cell-free assays, with an IC50 of 50 nM. In cellular models, it effectively inhibits BCAT activity, leading to increased intracellular levels of BCAAs and decreased production of their downstream metabolites. Its selectivity for BCATm over BCATc has been confirmed in vitro. It has also been used to study the role of BCAT activity in cancer cell proliferation and survival. |
| ln Vivo |
At a dose of 100 mg/kg, BCAT-IN-2 (Compound 61) (10-100 mg/kg; oral) raised leucine levels in mice from 473 μM to 1.2 mM [1]. BCAT-IN-2 has a long half-life (t1/2=9.2 h), low clearance rate (Cl=0.3 mL/min/kg), and high bioavailability (F=100%) in mice[1]. Its doses are 5 mg/kg for po and 1 mg/kg for iv.
In vivo, BCAT-IN-2 has been shown to increase serum levels of leucine, isoleucine, and valine in mice when administered at doses of 10, 30, or 100 mg/kg five hours prior to an amino acid bolus. This demonstrates its ability to engage its target and modulate BCAA metabolism in living animals. It is being studied for its potential effects on metabolic disorders, such as obesity and dyslipidemia. |
| Enzyme Assay |
The in vitro enzyme inhibition assay for BCAT-IN-2 is performed by incubating purified recombinant BCAT2 enzyme with varying concentrations of the inhibitor in the presence of its substrates, a branched-chain amino acid and α-ketoglutarate. The reaction is typically carried out in a suitable buffer, and the production of glutamate is quantified using a coupled enzymatic assay or by HPLC. The pIC50 or IC50 value is calculated from a dose-response curve.
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| Cell Assay |
To study its cellular effects, cells are treated with BCAT-IN-2, and the intracellular levels of BCAAs and their metabolites are measured by LC-MS/MS. The activity of BCAT can also be assessed by measuring the conversion of radiolabeled BCAAs. The effect on cell proliferation, viability, and metabolic flux is measured using standard assays.
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| Animal Protocol |
The in vivo activity of BCAT-IN-2 is assessed in mouse models. The compound is administered orally, and blood samples are collected to measure serum BCAA levels. The effect on BCAA metabolism in tissues like liver and muscle can also be analyzed. Pharmacodynamic studies are performed to assess target engagement and the time course of the effect.
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| ADME/Pharmacokinetics |
BCAT-IN-2 has a molecular weight of 377.78 g/mol and a molecular formula of C17H14ClF2N5O. It is soluble in DMSO at 50 mg/mL (132.35 mM). It is an orally active compound. It is typically stored at -20°C for long-term stability. Specific PK parameters, such as half-life and bioavailability, are not widely published.
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| Toxicity/Toxicokinetics |
Specific toxicological data for BCAT-IN-2 are not detailed, as it is a research compound. It is not intended for human or veterinary use. Standard laboratory safety precautions, including the use of personal protective equipment (PPE), should be followed when handling the compound. Its safety profile would be established through dedicated toxicology studies if it were to be developed further.
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| References | |
| Additional Infomation |
BCAT-IN-2 is a research compound used to study the role of BCAT2 in BCAA metabolism and its involvement in various diseases. It is a valuable tool for investigating metabolic reprogramming in cancer, neurological disorders, and metabolic diseases where altered BCAA metabolism plays a role. By disrupting BCAA metabolism, it affects cellular energy production and signaling pathways. It is not approved for clinical use.
|
| Molecular Formula |
C17H14CLF2N5O
|
|---|---|
| Molecular Weight |
377.775768756866
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| Exact Mass |
377.085
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| CAS # |
1800024-45-6
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| PubChem CID |
78319104
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| Appearance |
White to yellow solid powder
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| LogP |
3.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
729
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=C(C(=C(C=1)F)CNC1=C(C#N)C2=NC(=CC(N2N1)=O)CCC)F
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| InChi Key |
URTVEMYYYIZBNE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H14ClF2N5O/c1-2-3-10-6-15(26)25-17(23-10)11(7-21)16(24-25)22-8-12-13(19)4-9(18)5-14(12)20/h4-6,22,24H,2-3,8H2,1H3
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| Chemical Name |
2-[(4-chloro-2,6-difluorophenyl)methylamino]-7-oxo-5-propyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile
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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: 50 mg/mL (132.35 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.62 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 25.0 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 | 2.6470 mL | 13.2352 mL | 26.4704 mL | |
| 5 mM | 0.5294 mL | 2.6470 mL | 5.2941 mL | |
| 10 mM | 0.2647 mL | 1.3235 mL | 2.6470 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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