Background:: Cholangiocarcinoma is the second-largest liver cancer, and develops from the biliary epithelium, where it discretely progresses. Unfortunately, many patients miss the opportunity of performing surgery when diagnosed with cholangiocarcinoma, and due to its chemotherapeutic insensitivity, its control has always been considered difficult.Objective::Here, we present a case of stage 4 cholangiocarcinoma being controlled by the combination of chemotherapy with PD-1 and VEGF/VEGFR2 inhibitors.Methods::The patient is a 58-year-old male who was diagnosed with a progressed cholangiocarcinoma 2 years ago. From the beginning, metastases were discovered in multiple places, and the patient was unsuccessfully treated with 3 chemotherapy regimens. Therefore, a new therapeutic method was considered, and that involved the testing of a new combination of chemotherapy with PD-1 and VEGF/VEGFR2 inhibitors.Results::After 6 courses of treatment with this combination, the patient’s lesions became smaller and stable.Conclusion::Our case highlights the possibility of combining chemotherapy with PD-1 and VEGF/ VEGFR2 inhibitors for the treatment of cholangiocarcinoma patients. This combination may herald new hope for patients who run out of regimens.

BMC Chemistry

Design, synthesis, and biological investigations of new pyrazole derivatives as VEGFR2/CDK-2 inhibitors targeting liver cancer

Article

作者: Sofan, Mamdouh A. ; Elshihawy, Hosam A. ; Negm, Elham ; Sofan, Mamdouh A ; Nafie, Mohamed S. ; Salem, Manar G ; Nafie, Mohamed S ; Salem, Manar G. ; Elshihawy, Hosam A ; Elzamek, Aya A ; Elzamek, Aya A.

AbstractNew Series of N-Manniche bases 3,4 (a-c) and 5,6 (a-b) were synthesized through the reaction of benzaldehyde and amine with 3-methyl-4-(aryldiazenyl)-1H-pyrazol-5-ol derivatives 2(a-c), they were fully characterized by FT-IR, (1H, 13C) NMR data in addition to their mass spectra. The Structural Activity Relationship of the target compounds were examined for their cytotoxicity. Some newly synthesized compounds showed promising antiproliferation properties when tested against HepG2 cancer cells. Compounds 4a, 5a, and 6b showed potent cytotoxicity against HepG2 with IC50 values of 4.4, 3.46 and 2.52 µM compared to Sorafenib (IC50 = 2.051 µM) and Roscovitine (IC50 = 4.18 µM). Furthermore, they were safe against the THLE2 cells with higher IC50 values. Compound 6b exhibited promising dual VEGFR2/CDK-2 inhibition activities; it had an IC50 value of 0.2 μM with VEGFR2 inhibition of 93.2%, and it had an IC50 value of 0.458 μM with CDK-2 inhibition of 88.7%. In comparison to the untreated control group (0.95%), compounds 5a (38.32%) and 6b (42.9%) considerably increased the cell population in total apoptosis. In addition, compounds 5a and 6b arrested the cell population at G0-G1 and S phases, respectively. Molecular docking experiments confirmed the virtual binding mechanism of the most active drugs, which were found to have good binding affinities with both receptor active sites.

100 项与 CAIX/VEGFR2 inhibitors(Tanta University) 相关的药物交易

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