CP-31398 diHCl stabilizes the active conformation of p53 and promotes p53 activity in p53 mutant or wild-type cancer/tumor cells.

Physicochemical Properties

Molecular Formula	C22H28CL2N4O
Molecular Weight	435.39
Exact Mass	434.164
CAS #	1217195-61-3
Related CAS #	259199-65-0;1217195-61-3 (2HCl);
PubChem CID	56972205
Appearance	Light yellow to yellow solid powder
LogP	5.198
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	8
Heavy Atom Count	29
Complexity	448
Defined Atom Stereocenter Count	0
SMILES	CN(C)CCCNC1=NC(=NC2=CC=CC=C21)/C=C/C3=CC=C(C=C3)OC.Cl.Cl
InChi Key	WWIFDJIOGCGSBS-IVKCLRODSA-N
InChi Code	InChI=1S/C22H26N4O.2ClH/c1-26(2)16-6-15-23-22-19-7-4-5-8-20(19)24-21(25-22)14-11-17-9-12-18(27-3)13-10-17;;/h4-5,7-14H,6,15-16H2,1-3H3,(H,23,24,25);2*1H/b14-11+;;
Chemical Name	N-[2-[(E)-2-(4-methoxyphenyl)ethenyl]quinazolin-4-yl]-N',N'-dimethylpropane-1,3-diamine;dihydrochloride
Synonyms	CP-31398 dihydrochloride; CP 31398 dihydrochloride; CP31398 dihydrochloride
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 p53 mutant cells, CP-31398 (36.75 μM, 16 hours) activates p21[1]. In SW480 cells, CP-31398 (15 μg/mL, 20 hours) causes apoptosis and cell cycle arrest [2].
ln Vivo	In mice models, CP-31398 (100 mg/kg, orally) has strong anti-tumor efficacy [1].
Cell Assay	Western Blot Analysis[1] Cell Types: Saos-2 cells expressing transfected mutant p53. Tested Concentrations: 36.75 μM. Incubation Duration: 16 hrs (hours). Experimental Results: p21 was induced in cells expressing only mutant p53. Western Blot Analysis[3] Cell Types: LN-18 and U87MG cells. Tested Concentrations: 36μM. Incubation Duration: 16 hrs (hours). Experimental Results: diminished caspase 3 levels and induced caspase 7 cleavage.
Animal Protocol	Animal/Disease Models: Small human tumor xenografts in mice [1]. Doses: 100 mg/kg. Route of Administration: Orally, twice (two times) daily for 7 days. Experimental Results: A375.S2 tumor growth inhibition -50%.
References	[1]. Pharmacological rescue of mutant p53 conformation and function. Science. 1999 Dec 24;286(5449):2507-10. [2]. The Mutant p53-Conformation Modifying Drug, CP-31398, Can Induce Apoptosis of Human Cancer Cells and Can Stabilize Wild-Type p53 Protein. Cancer Biol Ther. Jan-Feb 2002;1(1):47-55. [3]. CP-31398, a novel p53-stabilizing agent, induces p53-dependent and p53-independent glioma cell death. Oncogene. 2003 Nov 13;22(51):8233-45.

Solubility Data

Solubility (In Vitro)

DMSO : ~200 mg/mL (~459.36 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 0.83 mg/mL (1.91 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: 0.83 mg/mL (1.91 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2968 mL	11.4840 mL	22.9679 mL
	5 mM	0.4594 mL	2.2968 mL	4.5936 mL
	10 mM	0.2297 mL	1.1484 mL	2.2968 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.