Nutlin carboxylic acid (MDM2 ligand 1) is a Nutlin 3-based MDM2 ligand. Nutlin carboxylic acid (MDM2 ligand 1) can be connected to the target protein ligand through a linker to form a PROTAC molecule.

Physicochemical Properties

Molecular Formula	C32H32CL2N4O6
Molecular Weight	639.5257
Exact Mass	638.169
CAS #	2249750-27-2
PubChem CID	138576186
Appearance	White to yellow solid powder
LogP	5
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	8
Heavy Atom Count	44
Complexity	1060
Defined Atom Stereocenter Count	2
SMILES	ClC1C([H])=C([H])C(=C([H])C=1[H])[C@]1([H])[C@]([H])(C2C([H])=C([H])C(=C([H])C=2[H])Cl)N=C(C2C([H])=C([H])C(=C([H])C=2OC([H])(C([H])([H])[H])C([H])([H])[H])OC([H])([H])[H])N1C(N1C([H])([H])C(N(C([H])([H])C(=O)O[H])C([H])([H])C1([H])[H])=O)=O
InChi Key	CYFZSMNCDNFMOG-XZWHSSHBSA-N
InChi Code	InChI=1S/C32H32Cl2N4O6/c1-19(2)44-26-16-24(43-3)12-13-25(26)31-35-29(20-4-8-22(33)9-5-20)30(21-6-10-23(34)11-7-21)38(31)32(42)37-15-14-36(18-28(40)41)27(39)17-37/h4-13,16,19,29-30H,14-15,17-18H2,1-3H3,(H,40,41)/t29-,30+/m0/s1
Chemical Name	2-[4-[(4S,5R)-4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazole-1-carbonyl]-2-oxopiperazin-1-yl]acetic 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

References

: Development of Protein Degradation Inducers of Androgen Receptor by Conjugation of Androgen Receptor Ligands and Inhibitor of Apoptosis Protein Ligands. J Med Chem. 2018 Jan 25;61(2):543-575.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~78.18 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.75 mg/mL (4.30 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 27.5 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: ≥ 2.75 mg/mL (4.30 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 27.5 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: ≥ 2.75 mg/mL (4.30 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 27.5 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	1.5636 mL	7.8182 mL	15.6365 mL
	5 mM	0.3127 mL	1.5636 mL	3.1273 mL
	10 mM	0.1564 mL	0.7818 mL	1.5636 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.