XYD049
Based on 1 Customer Validation
XYD049 is a CRBN-based molecular glue degrader targeting GSPT1, with a DC50 of 19 nM. XYD049 mediates the formation of a ternary complex between CRBN and GSPT1, thereby triggering CRBN- and proteasome-dependent degradation of GSPT1. By degrading GSPT1, XYD049 downregulates castration-resistant prostate cancer (CRPC)-related oncogenes, including BCL2, CDK2, E2F3, EGFR, HSP90B1, TMPRSS2, AR, AR-V7, PSA and c-Myc. XYD049 inhibits cancer cell growth and suppresses tumor growth in mice. XYD049 can be used for research on castration-resistant prostate cancer. XYD049 consists of a linker (black part) NH2-C5-NH-Boc (HY-W004710), a CRBN-based E3 ligase ligand (blue part) Thalidomide 4-fluoride (HY-41547), and a target protein ligand (red part) GSPT1 ligand-1 (HY-170821), among which the E3 ligase ligand plus linker forms the conjugate E3 Ligase Ligand-linker Conjugate 158 (HY-170822).
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- Purity: 99.46%
- CAS No.: 3006788-11-7
- 화학식: C35H35BrN6O10S
- 분자량:811.66
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
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Biological Activity
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CDK2 |
Bcl-2 |
HSP90AB1 |
XYD049 (Compound 7d) (0.1 nM-20 μM; 96 h) potently inhibits the proliferation of LNCaP, 22Rv1 and C4-2B cells, with the strongest inhibitory activity against 22Rv1 cells (IC50 = 0.007 μM)[1].
XYD049 (6.25-25 nM; 14 days) potently inhibits colony formation of 22Rv1 cells[1].
XYD049 (12-1000 nM; 1-18 h) potently induces dose- and time-dependent degradation of GSPT1 in 22Rv1 castration-resistant prostate cancer cells, with a DC50 of 19 nM[1].
XYD049 (500 nM; 6 h) allows the gradual recovery of GSPT1 protein levels in 22Rv1 cells after washout[1].
Degradation of GSPT1 induced by XYD049 (500 nM; 6 h, with 2 h pretreatment of 500 nM MG132 (HY-13259) or PS-341 (HY-10227)) in 22Rv1 castration-resistant prostate cancer cells depends on the proteasome pathway[1].
Degradation of GSPT1 in castration-resistant 22Rv1 prostate cancer cells induced by XYD049 (300 nM-500 nM; 6 h) depends on binding to CRBN[1].
XYD049 (0.12-3.33 μM) forms the DDB1ΔBPB-CRBNΔ40-XYD049 binary complex, which binds to GSPT1 in vitro with a Kd value of 0.93 μM[1].
XYD049 (0.1 nM-20 μM; 1.5 h at room temperature) potently promotes the formation of a ternary complex between GSPT1 and CRBN in vitro[1].
XYD049 (0-1000 nM; 12 h) downregulates the mRNA expression of BCL2, CDK2, E2F3, EGFR, HSP90B1, TMPRSS2, AR-FL, AR-V7, KLK3 and c-Myc, and reduces the protein expression levels of AR-FL, AR-V7, KLK3, c-Myc, BCL2, BCL-XL and MCL-1[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:castration-resistant prostate cancer (CRPC) cell lines LNCaP, 22Rv1, and C4-2B
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Concentration:0.1 nM, 10 nM, 1 μM, 20 μM
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Incubation Time:96 h
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Result:Inhibited proliferation of LNCaP cells with an IC50 of 0.034 μM.
Inhibited proliferation of 22Rv1 cells with an IC50 of 0.007 μM.
Inhibited proliferation of C4-2B cells with an IC50 of 0.374 μM.
Was ~200-fold more potent than BET PROTAC degrader 5 (dBET1) in 22Rv1 cells.
Was more potent than GSPT1 degrader 1 (CC-90009) in 22Rv1 cells.
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Cell Line:22Rv1 cells
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Concentration:6.25, 12.5, 25 nM
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Incubation Time:14 days
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Result:Potently suppressed colony formation of 22Rv1 CRPC cells at concentrations as low as 6.25 nM.
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Cell Line:22Rv1 CRPC cells
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Concentration:12, 37, 111, 333, 1000 nM (6 h or 18 h incubation); 300 nM (1-6 h incubation)
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Incubation Time:6 h, 18 h, 1 h, 2 h, 4 h
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Result:Induced dose- and time-dependent degradation of GSPT1 in 22Rv1 cells, with a DC50 of 19 nM.
Exhibited faster onset of GSPT1 downregulation than GSPT1 degrader 1 (CC-90009).
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Cell Line:22Rv1 CRPC cells
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Concentration:500 nM
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Incubation Time:6 h, followed by washout and incubation for 0-72 h
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Result:GSPT1 protein levels gradually recovered over time after removal of XYD049.
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Cell Line:22Rv1 CRPC cells
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Concentration:500 nM MG132 or PS-341 (pretreatment); 500 nM XYD049
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Incubation Time:2 h pretreatment, followed by 6 h incubation
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Result:Pretreatment with MG132 or PS-341 abolished the XYD049-induced reduction of GSPT1 protein levels.
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Cell Line:22Rv1 CRPC cells
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Concentration:1-5 μM pomalidomide (HY-10984) (pretreatment); 300 nM XYD049; 100 nM siCRBN-1 or siCRBN-2 (transfection); 500 nM XYD049
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Incubation Time:2 h pretreatment, followed by 6 h incubation; 48 h transfection, followed by 6 h incubation
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Result:Pretreatment with pomalidomide attenuated XYD049-induced GSPT1 degradation.
CRBN silencing abolished the XYD049-induced GSPT1 degradation effect.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD-SCID (4 weeks old, 17−20 g; injected subcutaneously with 3×106 22Rv1 tumor cells)[1]
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Dosage:10 mg/kg; 20 mg/kg
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Administration:i.p.; daily; 21 days
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Result:Achieved a tumor growth inhibition (TGI) of 44%.
Achieved a tumor growth inhibition (TGI) of 55%.
Exhibited good tolerability in mice, as monitored by body weight changes.
Chemical Information
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CAS No. 3006788-11-7
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Appearance Solid
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분자량 811.66
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화학식 C35H35BrN6O10S
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Color Light yellow to yellow
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SMILES
CC1=NOC2=CC(OCC(NCCCCCNC3=CC=CC(C(N4C5CCC(NC5=O)=O)=O)=C3C4=O)=O)=C(C=C21)NS(C6=C(C=CC(Br)=C6)OC)(=O)=O
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
용액&용해도
DMSO : 50 mg/mL (61.60 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
순도&문서
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Data Sheet (280 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 1.2320 mL | 6.1602 mL | 12.3204 mL | 30.8011 mL |
| 5 mM | 0.2464 mL | 1.2320 mL | 2.4641 mL | 6.1602 mL | |
| 10 mM | 0.1232 mL | 0.6160 mL | 1.2320 mL | 3.0801 mL | |
| 15 mM | 0.0821 mL | 0.4107 mL | 0.8214 mL | 2.0534 mL | |
| 20 mM | 0.0616 mL | 0.3080 mL | 0.6160 mL | 1.5401 mL | |
| 25 mM | 0.0493 mL | 0.2464 mL | 0.4928 mL | 1.2320 mL | |
| 30 mM | 0.0411 mL | 0.2053 mL | 0.4107 mL | 1.0267 mL | |
| 40 mM | 0.0308 mL | 0.1540 mL | 0.3080 mL | 0.7700 mL | |
| 50 mM | 0.0246 mL | 0.1232 mL | 0.2464 mL | 0.6160 mL | |
| 60 mM | 0.0205 mL | 0.1027 mL | 0.2053 mL | 0.5134 mL |
XYD049 Related Classifications
HY-170820 Related Classifications
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