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受注：045-509-1970 |
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化学情報
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder | |||
| 化学式 | C23H22FN3O3.2HCl |
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| 分子量 | 480.36 | CAS No. | 1360460-82-7 | ||||
| Solubility (25°C)* | 体外 | Water | 96 mg/mL (199.85 mM) | ||||
| DMSO | 48 mg/mL (99.92 mM) | ||||||
| Ethanol | Insoluble | ||||||
| 体内 （毎回新しく調製した物を用意してください） |
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | Anlotinib (AL3818) is a highly potent and selective VEGFR2 inhibitor with IC50 less than 1 nM. It has broad-spectrum antitumor potential in clinical trials. Please use saline solution rather than PBS for dilutions. PBS may cause precipitation. |
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| in vitro | Anlotinib occupies the ATP-binding pocket of VEGFR2 tyrosine kinase and shows high selectivity and inhibitory potency (IC 50 <1 nmol/L) for VEGFR2 relative to other tyrosine kinases. Anlotinib inhibits VEGFR2 and VEGFR3 with IC50 values of 0.2 and 0.7 nmol/L, respectively. The inhibitory potency of anlotinib against VEGFR1 is lower, with an IC50 value of 26.9 nmol/L. The IC50 values of anlotinib for inhibition of the PDGFR-related kinases c-Kit and PDGFRβ are 14.8 and 115.0 nmol/L, respectively. Anlotinib has little effect on the activity of other kinases, including c-Met, c-Src, EGFR and HER2, even at a concentration of 2000 nmol/L. Anlotinib inhibits VEGF-induced signaling and cell proliferation in HUVEC with picomolar IC50 values. However, micromolar concentrations of anlotinib are required to inhibit tumor cell proliferation directly in vitro. Anlotinib significantly inhibits HUVEC migration and tube formation; it also inhibits microvessel growth from explants of rat aorta in vitro[1]. |
| in vivo | Anlotinib decreases vascular density in tumor tissue in vivo. Compared with the well-known tyrosine kinase inhibitor sunitinib, once-daily oral dose of anlotinib shows broader and stronger in vivo antitumor efficacy and, in some models, causes tumor regression in nude mice. It is well-tolerated in mice. Anlotinib is efficacious at doses (1.5‐6 mg/kg daily) that are significantly lower than effective doses of other TKI, which require doses of 20‐100 mg/kg to achieve significant inhibition of tumor growth in mice[1]. In vivo, anlotinib has showed broad activity against human tumor xenograft models of the colon (SW-620), ovarian (SK-OV-3), liver (SMMC-7721), renal (Caki-1), glioma (U87MG), and non-small cell lung (Calu-3) during dosing period. In Sprague-Dawley rats and beagle dogs, anlotinib is rapidly absorbed from the gastrointestinal tracks after oral administration. The oral bioavailability is 23-45 % in rats and 47-74 % in dogs. Anlotinib exhibits large volume of distribution in both species. In rats, primary tissues, such as the lung, kidneys, liver, and heart, exhibit significant higher exposure levels to anlotinib compared with that in plasma. The exposure level in the brain is comparable with the corresponding plasma level. In tumor-bearing mice, anlotinib concentrates 2.4-2.6 times in tumor tissue than in plasma. In human, anlotinib exhibits a quite long t1/2 (96 ± 17 h), which appeared to be dose-independent[2]. The terminal half-life of anlotinib in dogs (22.8±11.0 h) is longer than that in rats (5.1±1.6 h). This difference appeares to be mainly associated with an interspecies difference in total plasma clearance (rats, 5.35±1.31 L/h/kg; dogs, 0.40±0.06 L/h/kg). In human plasma, anlotinib is predominantly bound to albumin and lipoproteins, rather than to α1-acid glycoprotein or γ-globulins[3]. |
プロトコル(参考用のみ)
| キナーゼアッセイ | Enzyme-linked immunosorbent assay | |
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| Inhibitory activity of anlotinib against tyrosine kinases was determined using ELISA. Reaction of ATP with tyrosine kinase was initiated in reaction buffer (50 mmol/L HEPES pH 7.4, 50 mmol/L MgCl2, 0.5 mmol/L MnCl2, 0.2 mmol/L Na3VO4, 1 mmol/L DTT) and incubated for 1 hour at 37°C in 96-well plates precoated with 20 μg/mL Poly(Glu,Tyr)4:1. The plate was incubated with PY99 antibody and then with HRP-conjugated anti-mouse IgG. After reaction with o-phenylenediamine solution and then termination with the addition of 2N H2SO4, absorbance was measured at 490 nm using a Synergy H4 Hybrid reader. | ||
| 細胞アッセイ | 細胞株 | HUVEC, Mo7e, U-87MG and A431 cells |
| 濃度 | 0-10 μM | |
| 反応時間 | 1.5 h | |
| 実験の流れ | Serum-starved HUVEC, Mo7e, U-87MG and A431 cells are treated with different concentrations of test agents for 1.5 h and then stimulated with vascular endothelial growth factor (VEGF; 20 ng/mL), stem cell factor-1 (SCF-1; 2.5 ng/mL), platelet-derived growth factor-BB (PDGF-BB; 10 ng/mL), or epidermal growth factor (EGF; 10 ng/mL) for 10 min, respectively. Cell lysates are probed with the indicated antibodies. |
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| 動物実験 | 動物モデル | human colon cancer SW620 xenograft model（Balb/cA-nude mice, 5-6 weeks old) |
| 投薬量 | 0.75, 1.5, 3 and 6 mg/kg | |
| 投与方法 | oral | |
参考
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Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：
| Autophagy inhibition improves the efficacy of anlotinib and PD-1 inhibitors in the treatment of NSCLC [ J Immunother Cancer, 2025, 13(9)e010812] | PubMed: 40983344 |
| N6-Methyladenosine modification mediated by METTL3 promotes DNA-PKcs expression to induce anlotinib resistance in osteosarcoma [ Clin Transl Med, 2025, 15(2):e70228] | PubMed: 39924638 |
| Exploiting collateral sensitivity in the evolution of resistance to tyrosine kinase inhibitors in soft tissue sarcomas [ Commun Biol, 2025, 8(1):1185] | PubMed: 40781553 |
| The endoplasmic reticulum stress-ferroptosis reciprocal signaling orchestrates anti-tumor effect of anlotinib in anaplastic thyroid cancer [ Cancer Cell Int, 2025, 25(1):310] | PubMed: 40841645 |
| Anlotinib enhances the anti-tumor activity of osimertinib in patients with non-small cell lung cancer by reversing drug resistance [ Transl Lung Cancer Res, 2025, 14(1):40-57] | PubMed: 39958207 |
| Development and validation of a UPLC-MS/MS method for almonertinib with its active metabolite HAS-719 and anlotinib in human plasma [ J Pharm Biomed Anal, 2025, 260:116766] | PubMed: 40054106 |
| Advancing the development of TRIP13 inhibitors: A high-throughput screening approach [ SLAS Discov, 2025, 33:100233] | PubMed: 40228580 |
| Protocol for constructing in vivo and in vitro models integrating clinical and proteomic subtypes of chordoma [ STAR Protoc, 2025, 6(2):103719] | PubMed: 40156836 |
| Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies [ Cell, 2024, 187(1):184-203.e28] | PubMed: 38181741 |
| Clinical-proteomic classification and precision treatment strategy of chordoma [ Cell Rep Med, 2024, 5(10):101757] | PubMed: 39368483 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。