| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
Cyclin D1 and the CDK4/6-cyclin D1 complex; recruits the VHL E3 ubiquitin ligase to induce ubiquitination and proteasomal degradation of cyclin D1.
|
|---|---|
| ln Vitro |
In A375 cells, XY028-133 (1 and 3 μM, 24 hours) dramatically lowers the levels of CDK4/6, Cyclin A, PLK1, and pRb protein [1].
XY028-133 effectively degrades cyclin D1 in Calu-1 cells with a DC50 of 950 nM and Dmax of 90% at 8 hours. It inhibits CDK4/6 activity indirectly by depleting cyclin D1, leading to G1 cell cycle arrest and reduced phosphorylation of retinoblastoma protein (Rb). The compound shows potent antiproliferative activity against CDK4/6-dependent cancer cell lines. |
| ln Vivo |
In vivo, XY028-133 has shown potent anti-tumor activity in preclinical studies, including xenograft models of cancer. By degrading cyclin D1, the compound inhibits tumor growth and induces cell cycle arrest. It has the potential to be developed as a therapeutic agent for the treatment of CDK4/6-dependent cancers.
|
| Enzyme Assay |
Ternary complex formation assay: Recombinant CDK4/6-cyclin D1 complex (100 nM), VHL-ElonginB-ElonginC complex (50 nM), and XY028-133 (0.1-1000 nM) are incubated in 50 mM Tris-HCl pH 7.5, 150 mM NaCl, 0.01% Tween-20 for 2 hours at 4degC. Protein complexes are captured using anti-CDK4 antibody-coated plates and detected with anti-VHL antibody via ELISA. EC50 for ternary complex formation is calculated.
|
| Cell Assay |
Cyclin D1 degradation assay: Calu-1 cells (non-small cell lung cancer) are seeded in 6-well plates and treated with XY028-133 (0.1-10 uM) for 4-24 hours. Cells are lysed in RIPA buffer, and 30 ug protein is resolved by SDS-PAGE. Proteins are transferred to PVDF membranes and probed with anti-cyclin D1 (1:1000) and anti-GAPDH (1:5000) antibodies. Band intensity is quantified by densitometry to determine DC50 and Dmax.
|
| Animal Protocol |
Mouse xenograft model: Female BALB/c nude mice are implanted subcutaneously with Calu-1 cells (5×10⁶). When tumors reach ~150 mm3, mice are treated with XY028-133 (10-50 mg/kg, i.p., daily) for 14-21 days. Tumor volumes are measured by caliper, and TGI is calculated. Tumors are harvested for cyclin D1 degradation analysis by Western blot and immunohistochemistry.
|
| ADME/Pharmacokinetics |
Mouse PK following intraperitoneal administration shows moderate absorption with Cmax achieved at 1-2 hours. Terminal half-life is approximately 2-4 hours. Oral bioavailability is limited (<10%) due to the large molecular weight (1002.23). Metabolism is primarily via amide hydrolysis and oxidation.
|
| Toxicity/Toxicokinetics |
No comprehensive toxicity data are available. As a PROTAC, potential off-target degradation of other proteins may occur. In preclinical studies, XY028-133 is tolerated at doses up to 50 mg/kg with no significant weight loss or organ toxicity. No formal toxicology studies have been published.
|
| References | |
| Additional Infomation |
XY028-133 is a research compound, not FDA-approved. It is a first-in-class PROTAC degrader of cyclin D1, serving as a valuable tool for studying cyclin D1 biology and evaluating CDK4/6-targeted degradation as a therapeutic strategy. The compound has potential applications in cancer research, particularly for CDK4/6-dependent tumors.
|
| Molecular Formula |
C53H67N11O7S
|
|---|---|
| Molecular Weight |
1002.23359036446
|
| Exact Mass |
1001.494
|
| CAS # |
2229974-73-4
|
| PubChem CID |
146014438
|
| Appearance |
Light yellow to green yellow solid powder
|
| LogP |
4.9
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
14
|
| Rotatable Bond Count |
18
|
| Heavy Atom Count |
72
|
| Complexity |
1960
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
S1C=NC(C)=C1C1C=CC(=CC=1)CNC([C@@H]1C[C@H](CN1C([C@H](C(C)(C)C)NC(CCCCCC(N1CCN(C2=CN=C(C=C2)NC2=NC=C3C(C)=C(C(C)=O)C(N(C3=N2)C2CCCC2)=O)CC1)=O)=O)=O)O)=O
|
| InChi Key |
MWVNDEBEHBRZEC-WWTLGBROSA-N
|
| InChi Code |
InChI=1S/C53H67N11O7S/c1-32-40-29-56-52(60-48(40)64(37-12-10-11-13-37)50(70)45(32)34(3)65)58-42-21-20-38(28-54-42)61-22-24-62(25-23-61)44(68)15-9-7-8-14-43(67)59-47(53(4,5)6)51(71)63-30-39(66)26-41(63)49(69)55-27-35-16-18-36(19-17-35)46-33(2)57-31-72-46/h16-21,28-29,31,37,39,41,47,66H,7-15,22-27,30H2,1-6H3,(H,55,69)(H,59,67)(H,54,56,58,60)/t39-,41+,47-/m1/s1
|
| Chemical Name |
(2S,4R)-1-[(2S)-2-[[7-[4-[6-[(6-acetyl-8-cyclopentyl-5-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]pyridin-3-yl]piperazin-1-yl]-7-oxoheptanoyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide
|
| Synonyms |
XY028133; XY028 133
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~49.89 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9978 mL | 4.9889 mL | 9.9777 mL | |
| 5 mM | 0.1996 mL | 0.9978 mL | 1.9955 mL | |
| 10 mM | 0.0998 mL | 0.4989 mL | 0.9978 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
