MI-1061 TFA is a potent, orally bioavailable, chemically stable MDM2 (MDM2-p53 interaction) inhibitor (IC50=4.4 nM; Ki=0.16 nM). MI-1061 TFA activates p53 and causes apoptosis in mouse SJSA-1 xenograft tumor tissue, showing anti-tumor activity.

Physicochemical Properties

Molecular Formula	C32H27CL2F4N3O6
Molecular Weight	696.47
Exact Mass	695.121
CAS #	1410737-35-7
Related CAS #	MI-1061;1410737-34-6
PubChem CID	155981982
Appearance	White to light yellow solid powder
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	4
Heavy Atom Count	47
Complexity	1090
Defined Atom Stereocenter Count	3
SMILES	C1=CC(C(=O)O)=CC=C1NC([C@@H]1NC2(CCCCC2)[C@@]2(C(=O)NC3=CC(Cl)=CC=C23)[C@H]1C1=CC=CC(Cl)=C1F)=O.OC(=O)C(F)(F)F
InChi Key	YVEFTHDIYIEZGS-FLLZXHAKSA-N
InChi Code	InChI=1S/C30H26Cl2FN3O4.C2HF3O2/c31-17-9-12-20-22(15-17)35-28(40)30(20)23(19-5-4-6-21(32)24(19)33)25(36-29(30)13-2-1-3-14-29)26(37)34-18-10-7-16(8-11-18)27(38)39;3-2(4,5)1(6)7/h4-12,15,23,25,36H,1-3,13-14H2,(H,34,37)(H,35,40)(H,38,39);(H,6,7)/t23-,25+,30+;/m0./s1
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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.
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	In the p53 knockout cell line HCT-116 p53–/–cell line, MI-1061 has an IC50>10000 nM, but in the SJSA-1 and HCT-116 p53+/+ cell lines, it obtains IC50=100 and 250 nM, respectively[1].
ln Vivo	In the SJSA-1 xenograft tumor model in mice, MI-1061 (100 mg/kg; po; daily for 14 days) can cause tumor regression[1].
Animal Protocol	Animal/Disease Models: SCID (severe combined immunodeficient) mouse bearing SJSA-1 osteosarcoma xenografts[1] Doses: 100 mg/kg Route of Administration: Po; daily for 14 days Experimental Results: Demonstrated strong antitumor activity and achieved significant tumor regression.
References	[1]. Design of chemically stable, potent, and efficacious MDM2 inhibitors that exploit the retro-mannich ring-opening-cyclization reaction mechanism in spiro-oxindoles. J Med Chem. 2014;57(24):10486-10498.

Solubility Data

Solubility (In Vitro)

DMSO : 120 mg/mL (172.30 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 3 mg/mL (4.31 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 30.0 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 2: ≥ 3 mg/mL (4.31 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 30.0 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	1.4358 mL	7.1791 mL	14.3581 mL
	5 mM	0.2872 mL	1.4358 mL	2.8716 mL
	10 mM	0.1436 mL	0.7179 mL	1.4358 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.