INCB28060(Capmatinib)
INCB28060是一种高效、口服生物利用度高的c-Met抑制剂，其IC??值为0.13nM。INCB28060用于治疗成人转移性非小细胞肺癌（NSCLC），包括Met外显子14跳跃产生的突变变体的NSCLC患者。
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包装价格促销价数量
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10mg￥1119.00780.00- +
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50mg￥2976.001650.00- +
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100mg￥5414.003000.00- +
- 货号: ajci19974
- CAS: 1029712-80-8
- 别名: 卡马替尼; INC280; INCB28060
- 分子式: C23H17FN6O
- 分子量: 412.42
- 纯度: ＞98%
- 溶解度: ≥ 5.15mg/mL in DMSO with gentle warming
- 储存: Store at -20°C
- 库存: 现货
Background
INCB28060 is a highly potent and orally bioavailable c-Met inhibitor with an IC?? value of 0.13nM[1]. INCB28060 is used to treat adults with metastatic non-small cell lung cancer (NSCLC), including those with NSCLC harboring mutations caused by MET exon 14 skipping[2]. INCB28060 has also demonstrated significant antitumor activity in preclinical models of various cancers, including glioma[3], and intrahepatic cholangiocarcinoma[4]
In vitro, pretreatment with INCB28060 (0–5nM) for 30 minutes to 2 hours in human umbilical vein endothelial cells (HUVECs) and THP-1 monocytes, followed by stimulation with LPS (200ng/ml) for 24 hours, significantly inhibits the expression of adhesion molecules, reduces the release of pro-inflammatory factors, and alleviates the inflammatory response[5]. Pretreatment of HepG2, Huh7, HeLa, and MCF-7 cells with INCB28060 (10μM) for 30 minutes, followed by incubation with different concentrations of doxorubicin (DOX), INCB28060 significantly enhances the apoptotic activity of DOX against cancer cell[6].
In vivo, INCB28060 (10mg/kg) administered orally once daily to a mouse model of NSCLC brain metastasis significantly inhibits the occurrence of brain metastasis and prolongs the survival time of the mice[7]. In a mouse model of diethylnitrosamine-induced acute liver injury, oral administration of INCB28060 (5 mg/kg) significantly reduces the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) in the serum. INCB28060 also alleviates hepatocellular ballooning and apoptosis, reduces the production and release of pro-inflammatory cytokines, and decreases the infiltration of inflammatory cells into the liver[8].
参考文献:
[1] Liu X, Wang Q, Yang G, et al. A novel kinase inhibitor, INCB28060, blocks c-MET-dependent signaling, neoplastic activities, and cross-talk with EGFR and HER-3. Clin Cancer Res. 2011 Nov 15;17(22):7127-38.
[2] Bi B, Zhan J, Fan B, et al. The pharmacokinetics of capmatinib and its efficacy in non-small cell lung cancer treatment: a narrative review. Transl Lung Cancer Res. 2025 Jul 31;14(7):2842-2852.
[3] Zuckermann M, He C, Andrews J, et al. Capmatinib is an effective treatment for MET-fusion driven pediatric high-grade glioma and synergizes with radiotherapy. Mol Cancer. 2024 Jun 7;23(1):123.
[4] Gautschi O, Menon R, Bertrand M, et al. Capmatinib and Osimertinib Combination Therapy for EGFR-Mutant Lung Adenocarcinoma. J Thorac Oncol. 2020 Jan;15(1):e13-e15.
[5] Park HS, Abd El-Aty AM, Jeong JH, et al. Capmatinib suppresses LPS-induced interaction between HUVECs and THP-1 monocytes through suppression of inflammatory responses. Biomed J. 2023 Apr;46(2):100534.
[6] Shaker ME, Shaaban AA, El-Shafey MM, et al. The selective c-Met inhibitor capmatinib offsets cisplatin-nephrotoxicity and doxorubicin-cardiotoxicity and improves their anticancer efficacies. Toxicol Appl Pharmacol. 2020 Jul 1;398:115018.
[7] Xia S, Duan W, Xu M, et al. Mesothelin promotes brain metastasis of non-small cell lung cancer by activating MET. J Exp Clin Cancer Res. 2024 Apr 3;43(1):103.
[8] Shaker ME, Ashamallah SA, El-Mesery M, et al. The novel c-Met inhibitor capmatinib mitigates diethylnitrosamine acute liver injury in mice. Toxicol Lett. 2016 Nov 2;261:13-25.
INCB28060是一种高效、口服生物利用度高的c-Met抑制剂，其IC??值为0.13nM[1]。INCB28060用于治疗成人转移性非小细胞肺癌（NSCLC），包括Met外显子14跳跃产生的突变变体的NSCLC患者[2]。同时INCB28060在多种癌症的临床前模型中表现出显著的抗肿瘤活性，包括神经胶质瘤[3]、肺腺癌[4]。
在体外，INCB28060（0–5nM）预处理人脐静脉内皮细胞（HUVECs）和THP-1单核细胞30分钟–2小时，随后以LPS（200ng/ml）刺激24小时，INCB28060显著抑制黏附分子的表达，同时降低促炎因子的释放，并减轻炎症反应[5]。INCB28060（10μM）预处理HepG2、Huh7、HeLa和MCF-7细胞30分钟，随后不同浓度阿霉素（DOX）孵育细胞， Chymostatin显著促进DOX对癌细胞的细胞凋亡活性[6]。
在体内，INCB28060（10mg/kg）处理非小细胞肺癌脑转移小鼠模型，每日一次口服给药，显著抑制脑转移的发生，并延长小鼠的生存时间[7]。INCB28060（5mg/kg）口服给药处理二乙基亚硝胺诱导急性肝损伤的小鼠模型，INCB28060显著降低血清中丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）和乳酸脱氢酶（LDH）的活性，减轻肝细胞气球样变性和凋亡，降低促炎细胞因子的产生和释放，并减少炎症细胞向肝脏的浸润[8]。
Protocol
| Cell experiment [1]: | |
Cell lines | Human umbilical vein endothelial cells (HUVECs) and THP-1 monocytes |
Preparation Method | HUVECs were cultured in M200PRF medium supplemented with a low-serum growth supplement mixture on 0.3% gelatin-coated culture plates. THP-1 cells were cultivated in RPMI 1640 media containing 10% fetal bovine serum, 100U/mL penicillin, and 100g/mL streptomycin. Cells were grown at 37°C in a humidified environment containing 5% CO?. For co-culture, THP-1 monocytes were harvested and treated with HUVECs. HUVECs and THP-1 were treated with INCB28060 (0–5nM) for 0.5-3 hours before treated with LPS (200ng/mL) 24h. |
Reaction Conditions | 0–5nM; 30min |
Applications | INCB28060 treatment significantly reduced the adhesion of THP-1 monocytes to HUVECs and the expression of adhesion molecules (ICAM-1, VCAM-1, and E-selectin) in HUVECs. INCB28060 also attenuated LPS-induced inflammatory responses, such as phosphorylation of NFκB and IκB, and the release of TNF-α and MCP-1 |
| Animal experiment [2]: | |
Animal models | BALB/c-nu mice |
Preparation Method | Mice were injected with PC9-BrM cells via the left ventricle. After 3 days, mice were randomly assigned to different treatment groups: control (placebo), anetumab (0.2mg/kg intravenously weekly), crizotinib (5mg/kg intraperitoneally every 2 days), anetumab + crizotinib, INCB28060 (10mg/kg orally daily), and anetumab + INCB28060. Treatments continued for 5 weeks. |
Dosage form | 10mg/kg; p.o. |
Applications | INCB28060 significantly inhibited the occurrence of brain metastasis (BM) in vivo and prolonged the survival of mice. Combined treatment with INCB28060 and anetumab showed improved survival rates. |
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