| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
PHGDH (phosphoglycerate dehydrogenase). BI-4916 is a prodrug that is converted to BI-4924, the active NADH/NAD+-competitive inhibitor of PHGDH. PHGDH is the first enzyme in the serine synthesis pathway, which is upregulated in various cancers to support biosynthesis and proliferation.
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|---|---|
| ln Vitro |
BI-4916, through its active metabolite BI-4924, inhibits PHGDH. BI-4924 is a NADH/NAD+-competitive inhibitor with high selectivity against other dehydrogenase targets. Inhibition of PHGDH blocks the serine synthesis pathway and can reduce cancer cell migration. The compound has applications in studying cancer and metabolic diseases.
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| ln Vivo |
In vivo, BI-4916 is converted to the active PHGDH inhibitor BI-4924. The compound induces hypoxia-like cellular responses under normal oxygen conditions. It is used in studies of oxygen sensing, red blood cell production, and metabolic regulation, and serves as a valuable tool in developing therapies for anemia and ischemic diseases.
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| Enzyme Assay |
PHGDH enzymatic activity is measured using a coupled enzyme assay. PHGDH converts 3-phosphoglycerate to 3-phosphohydroxypyruvate, producing NADH. The reaction is monitored by NADH absorbance or fluorescence. Recombinant PHGDH is incubated with substrate, NAD+, and serial dilutions of test compound (BI-4924 or BI-4916 with metabolic activation). IC₅0 values are calculated from dose-response curves.
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| Cell Assay |
Cancer cell lines (e.g., those with PHGDH amplification or serine synthesis pathway dependency) are treated with BI-4916 at various concentrations. Cell viability is assessed using MTT or CellTiter-Glo assays. Serine and glycine levels are measured by LC-MS/MS to confirm pathway inhibition. Cell migration is assessed using wound healing or transwell migration assays.
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| Animal Protocol |
Mice bearing subcutaneous tumor xenografts are administered BI-4916 orally or intravenously. Tumor growth is monitored, and tumors are harvested for pharmacodynamic analysis of PHGDH inhibition, serine levels, and proliferation markers. Efficacy is determined by tumor growth inhibition. The compound is also used in models of anemia and ischemic diseases.
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| ADME/Pharmacokinetics |
BI-4916 has a molecular weight of 527.42 g/mol and formula C23H24Cl2N2O₆S. As a prodrug, its PK properties include conversion to the active metabolite BI-4924. Standard PK parameters for both the prodrug and active metabolite would be determined in rodent studies following IV and PO administration.
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| Toxicity/Toxicokinetics |
Toxicology data for BI-4916 are not publicly available. As a prodrug targeting a metabolic enzyme, potential toxicities may arise from on-target effects on serine synthesis in normal tissues. Standard preclinical safety assessment would include cytotoxicity screening, hERG testing, and repeat-dose toxicology studies in rodents.
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| References | |
| Additional Infomation |
BI-4916 is a research compound for studying PHGDH biology, cancer metabolism, and metabolic diseases. It is not clinically approved. The prodrug approach provides improved drug-like properties and bioavailability compared to the active inhibitor BI-4924. BI-4916 is useful for investigating the role of the serine synthesis pathway in cancer and other diseases.
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| Molecular Formula |
C23H24CL2N2O6S
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|---|---|
| Molecular Weight |
527.417463302612
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| Exact Mass |
526.073
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| CAS # |
2244451-48-5
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| Related CAS # |
BI-4924;2244452-09-1
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| PubChem CID |
138911337
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| Appearance |
White to yellow solid powder
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| LogP |
3.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
34
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| Complexity |
830
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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)OCC)(=O)=O)=O)N2C)Cl
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| InChi Key |
HCDAVCLCBXIYPW-QGZVFWFLSA-N
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| InChi Code |
InChI=1S/C23H24Cl2N2O6S/c1-4-33-20(29)12-34(31,32)15-7-5-14(6-8-15)17(11-28)26-23(30)19-10-16-18(27(19)3)9-13(2)21(24)22(16)25/h5-10,17,28H,4,11-12H2,1-3H3,(H,26,30)/t17-/m1/s1
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| Chemical Name |
ethyl 2-[4-[(1S)-1-[(4,5-dichloro-1,6-dimethylindole-2-carbonyl)amino]-2-hydroxyethyl]phenyl]sulfonylacetate
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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 : ~250 mg/mL (~474.01 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.94 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 | 1.8960 mL | 9.4801 mL | 18.9602 mL | |
| 5 mM | 0.3792 mL | 1.8960 mL | 3.7920 mL | |
| 10 mM | 0.1896 mL | 0.9480 mL | 1.8960 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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