| Size | Price | Stock | Qty |
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| Other Sizes |
| Targets |
The primary target of BI-4924 is phosphoglycerate dehydrogenase (PHGDH), the first enzyme in the serine biosynthesis pathway. BI-4924 is an extremely effective purine dinucleotide (NADH/NAD+) competitive PHGDH oxidant. By inhibiting PHGDH, the compound disrupts the de novo synthesis of serine, which is crucial for cancer cell proliferation and survival. Its high selectivity and potency make it a valuable tool for studying serine metabolism.
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| ln Vitro |
BI-4924 is an extremely effective purine dinucleotide (NADH/NAD+) competitive PHGDH oxidant. BI-4924 has a high alkalinity toward most other dehydrogenase targets [1].
In vitro, BI-4924 is a potent and selective PHGDH inhibitor with an IC50 of 3 nM. It shows high alkalinity toward most other dehydrogenase targets, indicating good selectivity. Intracellularly captured BI-4924 disrupts serine biosynthesis with an IC50 of 2200 nM for 72 hours, demonstrating its cellular activity. It has excellent microsomal and hepatocyte stability. |
| ln Vivo |
In vivo efficacy data for BI-4924 are not extensively reported. As a potent and selective PHGDH inhibitor, it has potential for studying serine metabolism-driven cancers. Its lipophilic nature and high plasma protein binding may affect its bioavailability and distribution. Further in vivo studies are needed to evaluate its antitumor efficacy, pharmacokinetics, and safety profile.
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| Enzyme Assay |
For PHGDH inhibition assays, the enzymatic activity of recombinant PHGDH is measured. The enzyme is incubated with varying concentrations of BI-4924 in a reaction buffer containing the substrate (3-phosphoglycerate) and the cofactor (NAD+). The reaction is monitored by following the reduction of NAD+ to NADH at 340 nm or by using a coupled assay. IC50 values are calculated from dose-response curves.
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| Cell Assay |
For cellular studies, cancer cells are cultured in appropriate medium. BI-4924 is dissolved in DMSO and diluted in culture medium to final concentrations. Cells are treated for 24-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assays. Serine biosynthesis is assessed by measuring intracellular serine levels using LC-MS or by using a fluorescent serine sensor. PHGDH activity can be assessed by Western blot for downstream markers.
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| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice are implanted with cancer cells that are dependent on serine biosynthesis. BI-4924 is formulated in vehicle and administered orally or intraperitoneally. Tumor growth is monitored. At study termination, tumors are excised and processed for analysis of serine levels, PHGDH activity, and proliferation markers. Pharmacokinetic studies would assess compound levels in plasma and tissues.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of BI-4924 are not extensively reported. It is a lipophilic compound with high plasma protein binding. Its excellent microsomal and hepatocyte stability suggests it may have a favorable metabolic profile. However, specific parameters like half-life, oral bioavailability, and clearance would need to be determined through dedicated PK studies.
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| Toxicity/Toxicokinetics |
Toxicological data for BI-4924 are limited. No acute toxicity, organ-specific toxicity, or mutagenicity data have been reported. As with all research compounds, appropriate safety precautions should be taken when handling BI-4924, including the use of personal protective equipment.
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| References | |
| Additional Infomation |
BI-4924 (CAS 2244452-09-1) is a selective PHGDH inhibitor with an IC50 of 3 nM. It is lipophilic and highly plasma protein-bound. It has excellent microsomal and hepatocyte stability and disrupts serine biosynthesis. Its molecular formula is C₂₁H₂₀Cl₂N₂O₆S, and its molecular weight is 499.36. It is strictly for research use.
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| Molecular Formula |
C21H20CL2N2O6S
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|---|---|
| Molecular Weight |
499.364302635193
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| Exact Mass |
498.041
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| CAS # |
2244452-09-1
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| Related CAS # |
BI-4916;2244451-48-5
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| PubChem CID |
138756831
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| Appearance |
Off-white to yellow solid powder
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
32
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| Complexity |
799
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1=C(C(C)=CC2=C1C=C(C(N[C@H](CO)C1C=CC(=CC=1)S(CC(=O)O)(=O)=O)=O)N2C)Cl
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| InChi Key |
CJEJFFCPVBZSIE-OAHLLOKOSA-N
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| InChi Code |
InChI=1S/C21H20Cl2N2O6S/c1-11-7-16-14(20(23)19(11)22)8-17(25(16)2)21(29)24-15(9-26)12-3-5-13(6-4-12)32(30,31)10-18(27)28/h3-8,15,26H,9-10H2,1-2H3,(H,24,29)(H,27,28)/t15-/m1/s1
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| Chemical Name |
2-[4-[(1S)-1-[(4,5-dichloro-1,6-dimethylindole-2-carbonyl)amino]-2-hydroxyethyl]phenyl]sulfonylacetic acid
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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 : ~125 mg/mL (~250.32 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.17 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 (4.17 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.17 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0026 mL | 10.0128 mL | 20.0256 mL | |
| 5 mM | 0.4005 mL | 2.0026 mL | 4.0051 mL | |
| 10 mM | 0.2003 mL | 1.0013 mL | 2.0026 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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