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)).
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 分子式: C65H63F3N12O6
- 分子量:1165.27
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保管条件:
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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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
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生物活性
製品説明
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 |
体外実験
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
体内実験
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.
化学情報
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分子量 1165.27
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分子式 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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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
LD5095 関連分類
HY-189352 関連分類
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