| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
CDK6 4.4 nM (IC50)
YX-2-107 targets cyclin-dependent kinase 6 (CDK6) for selective degradation via the PROTAC mechanism. It recruits the CRBN E3 ubiquitin ligase to CDK6, leading to ubiquitination and proteasomal degradation. The compound shows selectivity for CDK6 over CDK4 with IC50 values of 0.69 nM for CDK4 and 4.4 nM for CDK6. |
|---|---|
| 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].
YX-2-107 effectively inhibits RB phosphorylation and FOXM1 expression in vitro. It selectively degrades CDK6 in Ph+ BV173 ALL cells with a degradation constant of 4 nM. The compound shows potent activity against various cancer cell lines. |
| 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].
YX-2-107 inhibits the development of Ph+ ALL in rats. In vivo efficacy is demonstrated in animal models of Philadelphia chromosome-positive acute lymphoblastic leukemia. The compound reduces tumor cell proliferation and enhances the effectiveness of existing cancer therapies. |
| Enzyme Assay |
In vitro assays measure CDK6 degradation using immunoblotting or mass spectrometry. IC50 values for degradation are determined by treating cells with increasing concentrations of YX-2-107 and quantifying the remaining CDK6 protein.
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| 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. Cell-based assays use Ph+ BV173 ALL cells to measure CDK6 degradation. RB phosphorylation and FOXM1 expression are assessed by Western blot analysis. Cell proliferation assays are used to evaluate the functional consequences of CDK6 degradation. |
| 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 In vivo efficacy is evaluated in rat models of Ph+ ALL. Tumor development is monitored to assess the inhibitory effect of YX-2-107. The compound's ability to inhibit tumor growth and progression is measured. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for YX-2-107 are limited. As a PROTAC molecule with a molecular weight typical of this class, it may have moderate oral bioavailability and tissue distribution. Further pharmacokinetic studies are needed to fully characterize its ADME properties.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data for YX-2-107 are limited. As a CDK6 degrader, it may have on-target toxicities related to CDK6 inhibition including myelosuppression. Standard laboratory safety precautions should be followed. Further toxicological studies are needed.
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| References | |
| Additional Infomation |
YX-2-107 is a selective CDK6-degrading PROTAC with an IC50 of 4.4 nM. It is a CRBN-recruiting PROTAC that shows selectivity for CDK6 over CDK4. The compound is a valuable research tool for studying CDK6 biology and has potential therapeutic applications in Ph+ ALL and other CDK6-dependent cancers.
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| Molecular Formula |
C45H51N11O9
|
|---|---|
| Molecular Weight |
889.954749345779
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| Exact Mass |
889.39
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| Elemental Analysis |
C, 60.73; H, 5.78; N, 17.31; O, 16.18
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| CAS # |
2417408-46-7
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| PubChem CID |
166642460
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| Appearance |
Yellow to orange solid powder
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| LogP |
1.3
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
16
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| Heavy Atom Count |
65
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| Complexity |
1880
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| Defined Atom Stereocenter Count |
0
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| 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
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| InChi Key |
JNYCZFGLJGFFEL-UHFFFAOYSA-N
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| 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)
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| 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
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| Synonyms |
YX-2-107; SCHEMBL24172331; CS-0634381
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : 100 mg/mL (112.37 mM)
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|---|---|
| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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