L18I
Based on 1 Customer Validation
L18I is a Bruton's tyrosine kinase (BTK) PROTAC degrader that targets wild-type and BTKC481, and recruits the cereblon E3 ligase to mediate proteasomal degradation. L18I regulates the BCR, TLR, FcγR and NLRP3 inflammasome signaling pathways, inhibits the phosphorylation of PLCγ-2, ERK1/2 and p38, and reduces the levels of B cell activation markers CD25, CD69 and CD86. L18I downregulates the NF-κB, TNF and TLR signaling pathways, reduces the production of pro-inflammatory cytokines, and decreases immune cell infiltration and immune complex deposition. L18I inhibits the proliferation of BTK-expressing lymphoma cells, induces tumor regression in xenograft models, and exhibits synergistic activity when combined with inhibitors of SYK, PI3K or Lyn. L18I can be used in research related to lupus, diffuse alveolar hemorrhage and B-cell lymphoma.
(Pink: Btk ligand (HY-13036A); Blue: Cereblon ligand (HY-43722); Black: linker (HY-41921)).
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。
- 純度: 99.43%
- CAS 番号: 2451070-32-7
- 分子式: C47H51N11O8
- 分子量:897.98
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保管条件:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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
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溶剤 & 溶解度
- 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
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BTK |
L18I potently degrades BTK in primary murine B cells with an EC50 of 15.36 nM[1].
L18I effectively degrades BTK in human THP1 monocytes[1].
L18I (2-1000 nM; 36 h) potently degrades C481S BTK in C481S BTK-overexpressing HBL-1 cells with a DC50 of 29 nM and a BTK half-life of <2 h[5].
L18I (10 nM-10 μM; 4 days) degrades all tested BTKC481 single-point mutants in transfected HeLa cells, with EC50 values ranging from 15 nM to 41 nM[5].
L18I (2-1000 nM; 36 h) inhibits phosphorylation of BCR pathway downstream proteins PLCγ-2, ERK1/2, and p38 in C481S BTK-overexpressing HBL-1 cells[5].
L18I reduces the upregulation of CD25, CD69, and CD86 activation markers in F(ab’)2 anti-mouse IgM-stimulated murine primary splenic B cells[1].
L18I reduces the upregulation of CD25, CD69, and CD86 activation markers in LPS-stimulated murine primary splenic B cells[1].
L18I (200 nM; 12 h) downregulates gene expression in the NF-κB, TLR, and TNF signaling pathways in LPS-stimulated primary mouse B cells[1].
L18I inhibits inflammatory cytokine upregulation in FcγR- or TLR-activated BMDMs[1].
L18I reduces Tnfa and Il1b transcription and IL-1β secretion in NLRP3 inflammasome-activated BMDMs[1].
L18I reduces TLR signaling pathway activation and downregulates ERK phosphorylation in LPS-stimulated Ramos B cells[1].
L18I reduces pro-inflammatory cytokine production in FcγR-, TLR-, or NLRP3 inflammasome-activated human THP1 monocytes[1].
L18I (36 h) degrades Cys481Ser mutant BTK in HBL1 B-cell lymphoma cells with a DC50 of ~30 nM at 36 h, and also degrades other Cys481-substituted BTK variants in these cells[3].
L18I (5-64 nM; < 2 h) potently degrades C481S and other C481-substituted BTK variants in human ABC-DLBCL HBL-1 cells (DC50 = 29 nM) and inhibits cell proliferation (GI50 = 64 nM), blocks downstream BCR signaling, shows activity in C481S BTK MCL cells, and exhibits synergistic antiproliferative effects with SYK and PI3K inhibitors[4].
L18I (72-96 h) inhibits proliferation of C481S BTK-overexpressing HBL-1 cells with a GI50 of 64 nM[5].
L18I (72-96 h) inhibits proliferation of BTK-overexpressing Mino and Z138 MCL cells with GI50 values of <10 nM[5].
L18I (72-96 h) combined with GS-9973 (Entospletinib) (HY-15968), Copanlisib (HY-15346), or Dasatinib (HY-10181) enhances inhibition of BTKC481S-overexpressing HBL-1 cell proliferation, with GI50 values ranging from <5 nM to 11 nM[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:C481S BTK-overexpressing HBL-1 (ABC-DLBCL) cells
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Concentration:2 nM; 4 nM; 8 nM; 16 nM; 31 nM; 62 nM; 125 nM; 250 nM; 500 nM; 1000 nM (concentration-dependent degradation); 100 nM (time-dependent degradation)
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Incubation Time:36 h (concentration-dependent degradation); 0-24 h (time-dependent degradation)
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Result:Induced concentration-dependent degradation of C481S BTK, with a half maximal degradative concentration (DC50) of 29 nM.
Reduced C481S BTK protein levels rapidly over time, with a BTK half-life of <2 h.
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Cell Line:Lipo2000-transfected HeLa cells expressing BTK C481 mutants (C481T, WT, C481S, C481G, C481W, C481A)
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Concentration:10 nM; 100 nM; 1 μM; 10 μM
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Incubation Time:4 days
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Result:Efficiently degraded all tested BTK C481 single-point mutants.
Achieved half maximal effective concentrations (EC50) of 38 nM for C481T, 18 nM for WT, 37 nM for C481S, 26 nM for C481G, 41 nM for C481W, and 15 nM for C481A.
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Cell Line:C481S BTK-overexpressing HBL-1 (ABC-DLBCL) cells
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Concentration:2 nM; 4 nM; 8 nM; 16 nM; 31 nM; 62 nM; 125 nM; 250 nM; 500 nM; 1000 nM
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Incubation Time:36 h
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Result:Potently inhibited phosphorylation of PLCγ-2, ERK1/2, and p38 in a concentration-dependent manner.
Left total PLCγ-2, ERK1/2, p38, and β-actin levels unchanged.
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Cell Line:C481S BTK-overexpressing HBL-1 (ABC-DLBCL) cells
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Concentration:Multiple concentrations (unspecified individual values)
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Incubation Time:72-96 h
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Result:Effectively inhibited growth of C481S BTK-overexpressing HBL-1 cells, with a half maximal growth-inhibitory concentration (GI50) of 64 nM.
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Cell Line:C481S BTK-overexpressing Mino and Z138 (MCL) cells
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Concentration:Multiple concentrations (unspecified individual values)
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Incubation Time:72-96 h
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Result:Efficiently halted proliferation of both C481S BTK-overexpressing Mino and Z138 MCL cells, with GI50 values of <10 nM for both cell lines.
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Cell Line:C481S BTK-overexpressing HBL-1 (ABC-DLBCL) cells
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Concentration:Multiple concentrations (unspecified individual values) plus 100 nM GS-9973; multiple concentrations (unspecified individual values) plus 70 nM copanlisib; multiple concentrations (unspecified individual values) plus unspecified dasatinib concentration
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Incubation Time:72-96 h
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Result:Reduced the GI50 of L18I to 11 nM when combined with 100 nM GS-9973.
Reduced the GI50 of L18I to <5 nM when combined with 70 nM copanlisib.
Reduced the GI50 of L18I to <5 nM when combined with dasatinib.
L18I (50-100 mg/kg; i.p.; once a day; 2 weeks) alleviates pristane-induced DAH in C57BL/6 mice by reducing disease prevalence, severity, monocyte infiltration, monocyte BTK levels, and improving survival[1].
L18I is well tolerated in short-term acute toxicity testing in B6 mice, with no observed mortality[3].
L18I (30-300 mg/kg; i.p.; daily; 14 days) induces dose-dependent tumor regression (36% reduction at 30 mg/kg, 63% reduction at 100 mg/kg) and reduces C481S BTK protein levels in a DLBCL xenograft model, while exhibiting high acute safety with 100% survival at doses up to 300 mg/kg[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 mice (n=6; lupus-like autoimmune disease induced by adoptive transfer of 1×107 BM12 splenocytes via i.v. injection)[1]
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Dosage:50 mg/kg
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Administration:i.p.; twice a day; 2 weeks
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Result:Reduced serum anti-dsDNA IgM and IgG titers relative to vehicle control.
Reduced serum IgM and IgG anti-nuclear antibody (ANA) mean fluorescence intensity (MFI) relative to vehicle control.
Reduced glomerular deposition of IgM and IgG antigen-antibody immune complexes (lower MFI for both IgM and IgG) relative to vehicle control.
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Animal Model:C57BL/6 mice (n=8 for prevalence/severity, n=6 for survival, n=5 for monocyte analysis/BTK degradation; DAH induced by i.p. injection of pristane, STS 0.3 mg/kg administered every 2 days for survival studies)[1]
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Dosage:50 mg/kg; 100 mg/kg
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Administration:i.p.; once a day; 2 weeks
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Result:Reduced DAH prevalence, with complete DAH rates lower than vehicle control; 100 mg/kg eliminated complete DAH.
Reduced DAH severity score relative to vehicle control, with 100 mg/kg showing greater reduction than 50 mg/kg.
Improved survival rate of DAH mice relative to vehicle control, with a significantly higher survival percentage at 20 days (50 mg/kg).
Reduced the proportion and absolute number of Ly6Cʰⁱ and Ly6Cˡᵒ monocytes in lung tissue relative to vehicle control (50 mg/kg).
Significantly reduced relative BTK protein levels in both Ly6Cʰⁱ and Ly6Cˡᵒ lung monocytes relative to vehicle control (50 mg/kg).
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Animal Model:B6[5]
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Dosage:30 mg/kg; 100 mg/kg; 250 mg/kg; 300 mg/kg
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Administration:i.p.; daily; 14 days (30 mg/kg, 100 mg/kg)
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Result:Reduced tumor size by 36% (p=0.0126) at 30 mg/kg.
Reduced tumor size by 63% (p=0.0004) at 100 mg/kg.
Lowered relative C481S BTK protein levels in tumors compared to vehicle group.
Maintained 100% survival and good health for 3 weeks post-treatment at 250 mg/kg and 300 mg/kg.
Showed minimal body weight loss compared to ibrutinib-treated mice.
化学情報
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CAS 番号 2451070-32-7
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性状 Solid
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分子量 897.98
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分子式 C47H51N11O8
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Color White to off-white
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SMILES
O=C1C2=CC=CC(CCCOCCOCCOCCN3C=C(C(N4CCC[C@@H](N5N=C(C6=CC=C(OC7=CC=CC=C7)C=C6)C8=C5N=CN=C8N)C4)=O)N=N3)=C2CN1C9C(NC(CC9)=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
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
溶剤 & 溶解度
DMSO : 100 mg/mL (111.36 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.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (2.78 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (2.78 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
純度とドキュメンテーション
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データシート (288 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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取扱説明書 (2659 KB)
参考文献
[1]. Zhu C, et al. PROTAC for Bruton's tyrosine kinase degradation alleviates inflammation in autoimmune diseases. Cell Discov. 2024 Aug 6;10(1):82. [Content Brief]
[2]. Song Y, et al. Targeted protein degradation in autoimmune diseases: from mechanisms to therapeutic breakthroughs. Journal of autoimmunity. 2025 Sep;156:103475. [Content Brief]
[3]. Arthur R, et al. Development of PROTACs to address clinical limitations associated with BTK-targeted kinase inhibitors. Exploration of targeted anti-tumor therapy. 2020 Jun 29;1(3):131-152. [Content Brief]
[4]. Wolska-Washer A, et al. Targeting Protein Degradation Pathways in Tumors: Focusing on their Role in Hematological Malignancies. Cancers. 2022 Aug 03;14(15):3778. [Content Brief]
[5]. Sun Y, et al. Degradation of Bruton's tyrosine kinase mutants by PROTACs for potential treatment of ibrutinib-resistant non-Hodgkin lymphomas. Leukemia. 2019 Aug;33(8):2105-2110. [Content Brief]
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 |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.1136 mL | 5.5681 mL | 11.1361 mL | 27.8403 mL |
| 5 mM | 0.2227 mL | 1.1136 mL | 2.2272 mL | 5.5681 mL | |
| 10 mM | 0.1114 mL | 0.5568 mL | 1.1136 mL | 2.7840 mL | |
| 15 mM | 0.0742 mL | 0.3712 mL | 0.7424 mL | 1.8560 mL | |
| 20 mM | 0.0557 mL | 0.2784 mL | 0.5568 mL | 1.3920 mL | |
| 25 mM | 0.0445 mL | 0.2227 mL | 0.4454 mL | 1.1136 mL | |
| 30 mM | 0.0371 mL | 0.1856 mL | 0.3712 mL | 0.9280 mL | |
| 40 mM | 0.0278 mL | 0.1392 mL | 0.2784 mL | 0.6960 mL | |
| 50 mM | 0.0223 mL | 0.1114 mL | 0.2227 mL | 0.5568 mL | |
| 60 mM | 0.0186 mL | 0.0928 mL | 0.1856 mL | 0.4640 mL | |
| 80 mM | 0.0139 mL | 0.0696 mL | 0.1392 mL | 0.3480 mL | |
| 100 mM | 0.0111 mL | 0.0557 mL | 0.1114 mL | 0.2784 mL |
L18I 関連分類
HY-163962 関連分類
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