CPS2 is a highly efficient, selective, irreversible PROTAC CDK2 degrader (IC50= 24 nM). CPS2 may be utilized to study acute myeloid leukemia.

Physicochemical Properties

Molecular Formula	C38H42N12O10S2
Molecular Weight	890.94
Exact Mass	890.258
CAS #	2756741-90-7
PubChem CID	155294157
Appearance	Yellow to green solid powder
Density	1.62±0.1 g/cm3(Predicted)
LogP	2.2
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	19
Rotatable Bond Count	21
Heavy Atom Count	62
Complexity	1690
Defined Atom Stereocenter Count	0
InChi Key	BXCPYBFBMAWDDY-UHFFFAOYSA-N
InChi Code	InChI=1S/C38H42N12O10S2/c1-23-11-20-61-32(23)36(55)50-37(39)44-38(46-50)42-24-5-7-26(8-6-24)62(56,57)41-13-16-60-22-25-21-48(47-45-25)14-17-59-19-18-58-15-12-40-28-4-2-3-27-31(28)35(54)49(34(27)53)29-9-10-30(51)43-33(29)52/h2-8,11,20-21,29,40-41H,9-10,12-19,22H2,1H3,(H,43,51,52)(H3,39,42,44,46)
Chemical Name	4-[[5-amino-1-(3-methylthiophene-2-carbonyl)-1,2,4-triazol-3-yl]amino]-N-[2-[[1-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethyl]triazol-4-yl]methoxy]ethyl]benzenesulfonamide
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

Targets	CDK2 24 nM (IC50)
ln Vitro	The most powerful degrader is CPS2 (5~333 nM; 12 hours; Ramos cells)[1]. HSCs are inhibited from proliferating by CPS2 (0.5~2 μM) without causing cytotoxicity. For 48 hours, CPS2 (1~10000 nM) in NB4 cells causes strong CDK2 degradation. Ramos and NB4 cells are exposed to 250 nM of CPS2, which rapidly causes CDK2 degradation in 0~6 hours. Under subnanomolar concentration levels, CPS2 (10~500 nM; 6 hours; Ramos cells) solely causes CDK2 degradation; it has no direct effect on the other CDK proteins. The most downregulated protein in cells treated with CPS2 for six hours was CPS2 (250 nM; NB4 cells), indicating that CPS2 is selective for CDK2. It is evident that CPS2 (0~250 nM; NB4 cells) causes a drop in CDK2 levels. It is evident that CPS2 (2 μM; 3 days; HL60 cells) enhances CD11b overexpression produced by ATRA[1]. Degradation of CDK2 mediates CPS2's antileukemic actions. By analyzing the morphology of the cells, CPS2 also causes HSCs to differentiate into granulocytes[1].
Cell Assay	Western Blot Analysis[1] Cell Types: Ramos cells Tested Concentrations: 5~333 nM Incubation Duration: 12 hrs (hours) Experimental Results: Stood out as the most potent degrader.
References	[1]. Discovery of a first-in-class CDK2 selective degrader for AML differentiation therapy. Nat Chem Biol. 2021;17(5):567-575.

Solubility Data

Solubility (In Vitro)

DMSO : 32.5 mg/mL (36.48 mM)

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.1224 mL	5.6121 mL	11.2241 mL
	5 mM	0.2245 mL	1.1224 mL	2.2448 mL
	10 mM	0.1122 mL	0.5612 mL	1.1224 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.