
| Name | Cyclin-dependent kinase 2 | ||
| UniProt ID | CDK2_HUMAN | ||
| Gene Name | CDK2 | ||
| Gene ID | 1017 | ||
| Synonyms |
CDK2, CDKN2, p33(CDK2)
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| Sequence |
MENFQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEGVPSTAIREISLLKELNH
PNIVKLLDVIHTENKLYLVFEFLHQDLKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHS HRVLHRDLKPQNLLINTEGAIKLADFGLARAFGVPVRTYTHEVVTLWYRAPEILLGCKYY STAVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDYKPSF PKWARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRISAKAALAHPFFQDVTKPVPHLRL |
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| Pathway Map | MAP LINK | ||
| KEGG ID | hsa1017 | ||
| TTD ID | T70176 | ||
| Pfam | PF00069; PF03109; PF07714; PF12330; PF14531 | ||
| Pair Name | 10-Gingerol, Doxorubicin | |||
| Phytochemical Name | 10-Gingerol | |||
| Anticancer drug Name | Doxorubicin | |||
| Disease Info | [ICD-11: 2C60] | Breast cancer | Investigative | |
| Regulate Info | Down-regulation | Cyclin-dependent kinase 2 | Expression | |
| Result | Our data indicate that [10]-gingerol has potential to be used as a neoadjuvant or in combined therapy with doxorubicin, to improve its anticancer activity. | |||
| Pair Name | Homoharringtonine, ACC010 | |||
| Phytochemical | Homoharringtonine | |||
| Drug | ACC010 | |||
| Disease Info | [ICD-11: 2A60.Z] | Acute myeloid leukemia | Investigative | |
| Regulate Info | Down-regulation | Cyclin-dependent kinase 2 | Expression | |
| Result | ACC010 and HHT cooperatively downregulated MYC and inhibited FLT3 activation. Further, when HHT was added, ACC010-resistant cells demonstrated a good synergy. We also extended our study to the mouse BaF3 cell line with FLT3-inhibitor-resistant FLT3-ITD/tyrosine kinase domain mutations and AML cells without FLT3-ITD. Collectively, our results suggested that the combination treatment of ACC010 and HHT might be a promising strategy for AML patients, especially those carrying FLT3-ITD. | |||
| Pair Name | Lycorine hydrochloride, Anti-CTLA-4 | |||
| Phytochemical | Lycorine hydrochloride | |||
| Drug | Anti-CTLA-4 | |||
| Disease Info | [ICD-11: 2C90.0] | Renal cell carcinoma | Investigative | |
| Regulate Info | Down-regulation | Cyclin-dependent kinase 2 | Expression | |
| Result | Synergistic effects of the immune checkpoint inhibitor CTLA-4 combined with the growth inhibitor lycorine in a mouse model of renal cell carcinoma | |||
| Pair Name | Berbamine, Arcyriaflavin A | |||
| Phytochemical | Berbamine | |||
| Drug | Arcyriaflavin A | |||
| Disease Info | [ICD-11: 2A00] | Glioblastoma multiforme | Investigative | |
| Regulate Info | Down-regulation | Cyclin-dependent kinase 2 | Expression | |
| Result | Our findings suggest that a novel combination therapy involving berbamine and ArcA could effectively eradicate glioblastoma stem-like cells. | |||
| Pair Name | Daurinoline, Sorafenib | |||
| Phytochemical | Daurinoline | |||
| Drug | Sorafenib | |||
| Disease Info | [ICD-11: 2C12] | Hepatocellular carcinoma | Investigative | |
| Regulate Info | Down-regulation | Cyclin-dependent kinase 2 | Expression | |
| Result | Our study provides insights into the molecular mechanisms underlying DS-induced inhibition of VM, which may facilitate the development of a novel clinical anti-HCC drug. Moreover, our findings suggest that the combination of DS and sorafenib constitutes a potential therapeutic strategy for HCC. | |||
| Pair Name | Nobiletin, Palbociclib | |||
| Phytochemical | Nobiletin | |||
| Drug | Palbociclib | |||
| Disease Info | [ICD-11: 2C90.0] | Renal cell carcinoma | Investigative | |
| Regulate Info | Down-regulation | Cyclin-dependent kinase 2 | Phosphorylation | |
| Result | Nobiletin downregulates the SKP2-p21/p27-CDK2 axis to inhibit tumor progression and shows synergistic effects with palbociclib on renal cell carcinoma | |||
| Pair Name | Tangeretin, Metformin | |||
| Phytochemical | Tangeretin | |||
| Drug | Metformin | |||
| Disease Info | [ICD-11: 2C60] | Breast cancer | Investigative | |
| Regulate Info | Down-regulation | Cyclin-dependent kinase 2 | Expression | |
| Result | The current work underscores the importance of metformin as an ERMA in tackling breast cancer and as a novel approach to boost its anticancer activity via a synergistic combination with tangeretin. | |||
| Pair Name | Oridonin, Venetoclax | |||
| Phytochemical | Oridonin | |||
| Drug | Venetoclax | |||
| Disease Info | [ICD-11: 2A60.Z] | Acute myeloid leukemia | Investigative | |
| Regulate Info | Down-regulation | Cyclin-dependent kinase 2 | Phosphorylation | |
| Result | Oridonin and venetoclax synergistically promote AML cell apoptosis by inhibiting AKT signaling. | |||
| Pair Name | Patchouli alcohol, Vincristine | |||
| Phytochemical | Patchouli alcohol | |||
| Drug | Vincristine | |||
| Disease Info | [ICD-11: 2C25.Z] | Lung cancer | Investigative | |
| Regulate Info | Down-regulation | Cyclin-dependent kinase 2 | Expression | |
| Result | Patchouli alcohol induces G0 /G1 cell cycle arrest and apoptosis in vincristine-resistant non-small cell lung cancer through ROS-mediated DNA damage | |||
| Pair Name | Thymoquinone, Fluorouracil | |||
| Phytochemical | Thymoquinone | |||
| Drug | Fluorouracil | |||
| Disease Info | [ICD-11: 2C60] | Breast cancer | Investigative | |
| Regulate Info | Down-regulation | Cyclin-dependent kinase 2 | Expression | |
| Result | TQ and 5-FU probably showed synergistic effect on both of cell cycle and apoptosis of tested TNBC cell lines. Our study reveals that TQ can synergise 5-FU action, and increase its anticancer efficiency against TNBC cells, which might be good choice in drug development for TNBC treatment. | |||
| Pair Name | Tenacissoside G, Fluorouracil | |||
| Phytochemical | Tenacissoside G | |||
| Drug | Fluorouracil | |||
| Disease Info | [ICD-11: 2B91.Z] | Colorectal cancer | Investigative | |
| Regulate Info | Down-regulation | Cyclin-dependent kinase 2 | Expression | |
| Result | TG potentiated 5-FU's inhibitory activity to human colorectal cancer through arresting cell cycle progression and inducing p53-mediated apoptosis, which may present a novel strategy in CRC therapies and contribute to the optimizing clinical application of 5-FU. | |||
| Pair Name | Pterostilbene, Sorafenib | |||
| Phytochemical | Pterostilbene | |||
| Drug | Sorafenib | |||
| Disease Info | [ICD-11: 2B72.Z] | Gastric cancer | Investigative | |
| Regulate Info | Down-regulation | Cyclin-dependent kinase 2 | Expression | |
| Result | PET obviously enhanced sorafenib's antitumour effects against GAC through inhibiting cell proliferation, inducing autophagy and promoting apoptosis. The combination therapy with PET and sorafenib may serve as a novel therapeutic strategy for treating GAC and deserve further clinical trials. | |||
| Pair Name | Polydatin, Paclitaxel | |||
| Phytochemical | Polydatin | |||
| Drug | Paclitaxel | |||
| Disease Info | [ICD-11: 2B51] | Osteosarcoma | Investigative | |
| Regulate Info | Down-regulation | Cyclin-dependent kinase 2 | Expression | |
| Result | Polydatin may enhance the chemosensitivity of osteosarcoma cells to paclitaxel. | |||
| Pair Name | Corilagin, Fluorouracil | |||
| Phytochemical | Corilagin | |||
| Drug | Fluorouracil | |||
| Disease Info | [ICD-11: 2B91.Z] | Colorectal cancer | Investigative | |
| Regulate Info | Down-regulation | Cyclin-dependent kinase 2 | Expression | |
| Result | Our results indicate that Corilagin acts as a potentiator of 5-fluorouracil and may have therapeutic potential for patients with CRC. | |||
| Pair Name | Sulforaphane, Everolimus | |||
| Phytochemical | Sulforaphane | |||
| Drug | Everolimus | |||
| Disease Info | [ICD-11: 2C94.Z] | Bladder cancer | Investigative | |
| Regulate Info | Down-regulation | Cyclin-dependent kinase 2 | Phosphorylation | |
| Result | The addition of SFN to the long-term everolimus application inhibits resistance development in bladder cancer cells in vitro. Therefore, sulforaphane may hold potential for treating bladder carcinoma in patients with resistance to an mTOR inhibitor. | |||
| Pair Name | Zeylenone, Cisplatin | |||
| Phytochemical | Zeylenone | |||
| Drug | Cisplatin | |||
| Disease Info | [ICD-11: 2B51] | Osteosarcoma | Investigative | |
| Regulate Info | Down-regulation | Cyclin-dependent kinase 2 | Expression | |
| Result | Zeylenone synergizes with cisplatin in osteosarcoma by enhancing DNA damage, apoptosis, and necrosis via the Hsp90/AKT/GSK3β and Fanconi anaemia pathway | |||
| Pair Name | Periplocin, Gemcitabine | |||
| Phytochemical | Periplocin | |||
| Drug | Gemcitabine | |||
| Disease Info | [ICD-11: 2C10.Z] | Pancreatic cancer | Investigative | |
| Regulate Info | Down-regulation | Cyclin-dependent kinase 2 | Expression | |
| Result | Periplocin exerts antitumor activity by regulating Nrf2-mediated signaling pathway in gemcitabine-resistant pancreatic cancer cells | |||
| Pair Name | Polyphyllin I, Palbociclib | |||
| Phytochemical | Polyphyllin I | |||
| Drug | Palbociclib | |||
| Disease Info | [ICD-11: 2C25.Z] | Lung cancer | Investigative | |
| Regulate Info | Down-regulation | Cyclin-dependent kinase 2 | Phosphorylation | |
| Result | We first time demonstrated PPI can disturb CDK2 function through upregulation of p21. The PPI effect on CDK2 provides a choice for a chemotherapeutic strategy for the elimination of NSCLC. Our study highlighted the clinical significance of simultaneously blocking of CDK2 and CDK4/6 for NSCLC treatment. | |||
| No. | Title | Href |
|---|---|---|
| 1 | [10]-Gingerol improves doxorubicin anticancer activity and decreases its side effects in triple negative breast cancer models. Cell Oncol (Dordr). 2020 Oct;43(5):915-929. doi: 10.1007/s13402-020-00539-z. | Click |
| 2 | ACC010, a novel BRD4 inhibitor, synergized with homoharringtonine in acute myeloid leukemia with FLT3-ITD. Mol Oncol. 2023 Jul;17(7):1402-1418. doi: 10.1002/1878-0261.13368. | Click |
| 3 | Synergistic effects of the immune checkpoint inhibitor CTLA-4 combined with the growth inhibitor lycorine in a mouse model of renal cell carcinoma. Oncotarget. 2017 Mar 28;8(13):21177-21186. doi: 10.18632/oncotarget.15505. | Click |
| 4 | Synergistic Anticancer Effect of a Combination of Berbamine and Arcyriaflavin A against Glioblastoma Stem-like Cells. Molecules. 2022 Nov 17;27(22):7968. doi: 10.3390/molecules27227968. | Click |
| 5 | The role of daurisoline treatment in hepatocellular carcinoma: Inhibiting vasculogenic mimicry formation and enhancing sensitivity to sorafenib. Phytomedicine. 2021 Nov;92:153740. doi: 10.1016/j.phymed.2021.153740. | Click |
| 6 | Nobiletin downregulates the SKP2-p21/p27-CDK2 axis to inhibit tumor progression and shows synergistic effects with palbociclib on renal cell carcinoma. Cancer Biol Med. 2021 Feb 15;18(1):227-244. doi: 10.20892/j.issn.2095-3941.2020.0186. | Click |
| 7 | Tangeretin boosts the anticancer activity of metformin in breast cancer cells via curbing the energy production. Phytomedicine. 2021 Mar;83:153470. doi: 10.1016/j.phymed.2021.153470. | Click |
| 8 | Oridonin Synergistically Enhances the Pro-Apoptotic Effect of Venetoclax on Acute Myeloid Leukemia Cells by Inhibiting AKT Signaling. Front Biosci (Landmark Ed). 2023 Sep 6;28(9):195. doi: 10.31083/j.fbl2809195. | Click |
| 9 | Patchouli alcohol induces G0 /G1 cell cycle arrest and apoptosis in vincristine-resistant non-small cell lung cancer through ROS-mediated DNA damage. Thorac Cancer. 2023 Jul;14(21):2007-2017. doi: 10.1111/1759-7714.14982. | Click |
| 10 | Synergistic Role of Thymoquinone on Anticancer Activity of 5-Fluorouracil in Triple Negative Breast Cancer Cells. Anticancer Agents Med Chem. 2022;22(6):1111-1118. doi: 10.2174/1871520621666210624111613. | Click |
| 11 | Tenacissoside G synergistically potentiates inhibitory effects of 5-fluorouracil to human colorectal cancer. Phytomedicine. 2021 Jun;86:153553. doi: 10.1016/j.phymed.2021.153553. | Click |
| 12 | Pterostilbene enhances sorafenib's anticancer effects on gastric adenocarcinoma. J Cell Mol Med. 2020 Nov;24(21):12525-12536. doi: 10.1111/jcmm.15795. | Click |
| 13 | Polydatin enhances the chemosensitivity of osteosarcoma cells to paclitaxel. J Cell Biochem. 2019 Oct;120(10):17481-17490. doi: 10.1002/jcb.29012. | Click |
| 14 | Corilagin enhances the anti-tumor activity of 5-FU by downregulating the expression of GRP 78. Sci Rep. 2023 Dec 19;13(1):22661. doi: 10.1038/s41598-023-49604-1. | Click |
| 15 | Chronic Sulforaphane Administration Inhibits Resistance to the mTOR-Inhibitor Everolimus in Bladder Cancer Cells. Int J Mol Sci. 2020 Jun 4;21(11):4026. doi: 10.3390/ijms21114026. | Click |
| 16 | Zeylenone synergizes with cisplatin in osteosarcoma by enhancing DNA damage, apoptosis, and necrosis via the Hsp90/AKT/GSK3β and Fanconi anaemia pathway. Phytother Res. 2021 Oct;35(10):5899-5918. doi: 10.1002/ptr.7299 | Click |
| 17 | Periplocin exerts antitumor activity by regulating Nrf2-mediated signaling pathway in gemcitabine-resistant pancreatic cancer cells. Biomed Pharmacother. 2023 Jan;157:114039. doi: 10.1016/j.biopha.2022.114039. | Click |
| 18 | Polyphyllin I, a lethal partner of Palbociclib, suppresses non-small cell lung cancer through activation of p21/CDK2/Rb pathway in vitro and in vivo. Cell Cycle. 2021 Dec;20(23):2494-2506. doi: 10.1080/15384101.2021.1991121. | Click |