YX-2-107 is a PROTAC that selectively degrades CDK6 (IC50= 4.4 nM). YX-2-107 can effectively inhibit RB phosphorylation and FOXM1 expression in vitro, and inhibit the development of Ph+ ALL in rats. YX-2-107 may be utilized in the research of Ph chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).

Physicochemical Properties

Molecular Formula	C45H51N11O9
Molecular Weight	889.954749345779
Exact Mass	889.39
Elemental Analysis	C, 60.73; H, 5.78; N, 17.31; O, 16.18
CAS #	2417408-46-7
PubChem CID	166642460
Appearance	Yellow to orange solid powder
LogP	1.3
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	15
Rotatable Bond Count	16
Heavy Atom Count	65
Complexity	1880
Defined Atom Stereocenter Count	0
SMILES	C(NCCCCNCC(N1CCN(C2=CC=C(NC3=NC=C4C(C)=C(C(C)=O)C(=O)N(C5CCCC5)C4=N3)N=C2)CC1)=O)(=O)COC1=CC=CC2=C1C(=O)N(C1CCC(=O)NC1=O)C2=O
InChi Key	JNYCZFGLJGFFEL-UHFFFAOYSA-N
InChi Code	InChI=1S/C45H51N11O9/c1-26-31-23-49-45(52-40(31)55(28-8-3-4-9-28)43(63)38(26)27(2)57)50-34-14-12-29(22-48-34)53-18-20-54(21-19-53)37(60)24-46-16-5-6-17-47-36(59)25-65-33-11-7-10-30-39(33)44(64)56(42(30)62)32-13-15-35(58)51-41(32)61/h7,10-12,14,22-23,28,32,46H,3-6,8-9,13,15-21,24-25H2,1-2H3,(H,47,59)(H,51,58,61)(H,48,49,50,52)
Chemical Name	N-(4-((2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)-2-oxoethyl)amino)butyl)-2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamide
Synonyms	YX-2-107; SCHEMBL24172331; CS-0634381
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	CDK6 4.4 nM (IC50)
ln Vitro	In Ph+ BV173 and SUP-B15 cells, YX-2-107 (2000 nM; 48 h) inhibits the S phase[1]. CDK6 in BV173 cells is selectively degraded by YX-2-107 (0, 1.6, 8, 40, 200, and 1000 nM; 4 h)[1]. Ph+ BV173 and SUP-B15 cells' RB phosphorylation and FOXM1 expression are inhibited by YX-2-107 (2000 nM; 72 h)[1].
ln Vivo	After 4 hours, YX-2-107 (10 mg/kg; ip; single) is cleared from the plasma at a maximum concentration of 741 nM, which is 150 times higher than the CDK6 degradation IC50[1]. Pharmacologically, YX-2-107 (150 mg/kg; ip; once daily for three days) inhibits the growth of Ph+ ALL in mice[1].
Cell Assay	Cell Cycle Analysis[1] Cell Types: Ph+ BV173 and SUP-B15 cells Tested Concentrations: 2000 nM Incubation Duration: 48 h Experimental Results: Inhibited S-phase entry. Western Blot Analysis[1] Cell Types: Ph+ BV173 and SUP-B15 cells Tested Concentrations: 2000 nM Incubation Duration: 72 h Experimental Results: Inhibited the phosphorylation of RB and the expression of FOXM1.
Animal Protocol	Animal/Disease Models: NRG- SGM3 mice (Ph+ ALL xenografts model)[1]. Doses: 150 mg/kg Route of Administration: intraperitoneal (ip)injection; single daily for 3 days Experimental Results: Suppressed the percentage of primary Ph+ ALL S-phase cells, the expression of CDK4/6-regulated phospho-RB and, to a lesser degree, FOXM1, and induced the selective CDK6 degradation. Animal/Disease Models: C57BL/6j mice[1]. Doses: 10 mg/kg Route of Administration: intraperitoneal (ip)injection; single Experimental Results: 1.19 pharmacokinetic/PK Parameters of YX- 2-107 in C57BL/6j mice [1]. IP (10 mg/kg) Tmax (h) 0.5 Cmax (ng/mL) 660 AUC0-t (ng/mL·h) 815 AUC0-∞ (ng/mL· h) 987
References	[1]. Selective inhibition of Ph-positive ALL cell growth through kinase-dependent and -independent effects by CDK6-specific PROTACs. Blood. 2020 Apr 30;135(18):1560-1573.

Solubility Data

Solubility (In Vitro)

DMSO : 100 mg/mL (112.37 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (2.81 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 25.0 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.1237 mL	5.6183 mL	11.2366 mL
	5 mM	0.2247 mL	1.1237 mL	2.2473 mL
	10 mM	0.1124 mL	0.5618 mL	1.1237 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.