BI-4924 is a lipophilic, highly plasma protein-binding and selective phosphoglycerate dehydrogenase (PHGDH) inhibitor (IC50=3 nM) with excellent microsomal and hepatocyte stability. Intracellularly captured BI-4924 disrupts serine biosynthesis with IC50 of 2200 nM for 72 hours.

Physicochemical Properties

Molecular Formula	C21H20CL2N2O6S
Molecular Weight	499.364302635193
Exact Mass	498.041
CAS #	2244452-09-1
Related CAS #	BI-4916;2244451-48-5
PubChem CID	138756831
Appearance	Off-white to yellow solid powder
LogP	2.9
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	7
Heavy Atom Count	32
Complexity	799
Defined Atom Stereocenter Count	1
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
InChi Key	CJEJFFCPVBZSIE-OAHLLOKOSA-N
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
Chemical Name	2-[4-[(1S)-1-[(4,5-dichloro-1,6-dimethylindole-2-carbonyl)amino]-2-hydroxyethyl]phenyl]sulfonylacetic acid
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

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].
References	[1]. Intracellular Trapping of the Selective Phosphoglycerate Dehydrogenase (PHGDH) Inhibitor BI-4924 Disrupts Serine Biosynthesis. J Med Chem. 2019 Jul 31.

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~250.32 mM)

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. 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. 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	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.