LD5095
LD5095 is a potent and orally active RIPK1 PROTAC degrader with a DC50 of 1.4 nM. LD5095 induces ubiquitination and degradation of RIPK1 target protein by recruiting Cereblon E3 ligase. LD5095 can be used for leukemia research.
(Pink: RIPK1 ligand (HY-179235); Blue: Cereblon E3 ligase ligand; Black: linker (HY-189354)).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Fòrmula: C65H63F3N12O6
- Peso molecular:1165.27
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
hRIP1 1.4 nM (DC50) |
Cereblon |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| Jurkat | DC50 |
2.5 nM
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Degradation of nLuc-RIPK1 in Jurkat cells expressing nLuc-RIPK1 treated with LD5095 for 24 hrs, measured by Nano-Glo Luciferase assay.
Degradation of nLuc-RIPK1 in Jurkat cells expressing nLuc-RIPK1 treated with LD5095 for 24 hrs, measured by Nano-Glo Luciferase assay.
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PMC13105033 |
| Jurkat | DC50 |
1.4 nM
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Degradation of endogenous RIPK1 in wild-type Jurkat cells treated with serially diluted LD5095 for 24 hrs, assessed by Western blot analysis.
Degradation of endogenous RIPK1 in wild-type Jurkat cells treated with serially diluted LD5095 for 24 hrs, assessed by Western blot analysis.
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PMC13105033 |
| MOLM-14 | DC50 |
1.2 nM
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Degradation of endogenous RIPK1 in MOLM14 cells treated with serially diluted LD5095 for 24 hrs, assessed by Western blot analysis.
Degradation of endogenous RIPK1 in MOLM14 cells treated with serially diluted LD5095 for 24 hrs, assessed by Western blot analysis.
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PMC13105033 |
| U-937 | DC50 |
2.3 nM
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Degradation of endogenous RIPK1 in U937 cells treated with serially diluted LD5095 for 24 hrs, assessed by Western blot analysis.
Degradation of endogenous RIPK1 in U937 cells treated with serially diluted LD5095 for 24 hrs, assessed by Western blot analysis.
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PMC13105033 |
| MOLM-14 | IC50 |
1.186 μM
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Antiproliferative activity against human MOLM14 cells assessed as reduction in cell viability.
Antiproliferative activity against human MOLM14 cells assessed as reduction in cell viability.
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PMC13105033 |
| U-937 | IC50 |
2.322 μM
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Antiproliferative activity against human U937 cells assessed as reduction in cell viability.
Antiproliferative activity against human U937 cells assessed as reduction in cell viability.
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PMC13105033 |
In Vitro
LD5095 (100 nM; 72 h) in combination with TNFα (HY-P7058) treatment significantly reduces cell viability and sensitizes Jurkat cells to TNFα-mediated apoptosis, increasing the expression of apoptosis markers[1].
LD5095 (1.6 nM-1 μM; 24 h) dose-dependently and potently degrades endogenous RIPK1 protein in Jurkat (DC50 = 1.4 nM), MOLM14 (DC50 = 1.2 nM), and U937 (DC50 = 2.3 nM) cells[1].
LD5095 (100 nM; 0.5-24 h) rapidly and time-dependently degrades RIPK1 protein in Jurkat cells, achieving complete degradation within 4 h[1].
LD5095 (100 nM; 6 h) highly selectively degrades RIPK1 protein in MOLM14 cells without degrading off-target kinases[1].
LD5095 (100 nM; 24 h) does not affect RIPK1 mRNA levels in Jurkat cells, confirming a post-translational degradation mechanism[1].
LD5095 (72 h) treatment as a single agent does not produce significant cytotoxicity or inhibit cell proliferation in Jurkat, MOLM14, U937 cells, as well as human primary B cells, T cells, and PBMCs[1].
LD5095 (100 nM; 4 h) combined with Carfilzomib (HY-10455) pretreatment induces ubiquitination of RIPK1 in Jurkat cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. .
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Cell Line:Jurkat, MOLM14, U937 cells
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Concentration:1.6 nM, 8 nM, 40 nM, 200 nM, 1000 nM
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Incubation Time:24 h
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Result:Degraded endogenous RIPK1 protein in a dose-dependent manner, achieving maximum degradation at 200 nM.
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Cell Line:Jurkat cells
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Concentration:200 nM
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Incubation Time:0.5 h, 1 h, 2 h, 4 h, 6 h, 12 h, 24 h
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Result:Triggered rapid RIPK1 degradation, achieving complete degradation within 4 hours.
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Cell Line:Jurkat cells
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Concentration:100 nM (with or without 100 ng/mL TNFα)
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Incubation Time:72 h
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Result:Greatly enhanced the proportion of cells undergoing TNFα-induced apoptosis.
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Cell Line:Jurkat cells
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Concentration:100 nM
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Incubation Time:24 h
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Result:Did not alter the mRNA expression of RIPK1.
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Nude mice (6-week-old female)[1]
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Dosage:10 mg/kg
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Administration:i.v.; single dose; 6, 24, 144 h
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Result:Significantly reduced RIPK1 protein levels in tumor tissues by >55% at 6 hours post-administration.
Reduced RIPK1 protein levels by 52% at 24 hours post-administration.
Maintained highly potent efficacy, reducing RIPK1 protein levels by 85% at 144 hours (6 days) post-administration.
Chemical Information
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Peso molecular 1165.27
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Fòrmula C65H63F3N12O6
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SMILES
NC1=C2C(C3=CC4=C(N(CC4)C(CC5=CC=CC(OC(F)(F)F)=C5)=O)C=C3)=CN(C2=NC=N1)C6CCN(CC6)C(C7=CC=C(C=C7)C#CC8=CN=C(C=C8)N9CC%10(C9)CN(C%10)C(CN%11CCC(CC%11)C%12=CC=C(C=C%12)NC%13CCC(NC%13=O)=O)=O)=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
LD5095 Related Classifications
HY-189352 Related Classifications
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