InterPAD - DETAILS

MENFQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEGVPSTAIREISLLKELNH
PNIVKLLDVIHTENKLYLVFEFLHQDLKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHS
HRVLHRDLKPQNLLINTEGAIKLADFGLARAFGVPVRTYTHEVVTLWYRAPEILLGCKYY
STAVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDYKPSF
PKWARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRISAKAALAHPFFQDVTKPVPHLRL

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	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`
3	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`
4	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`
5	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`
6	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`
7	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`
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	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`
11	Polydatin enhances the chemosensitivity of osteosarcoma cells to paclitaxel. J Cell Biochem. 2019 Oct;120(10):17481-17490. doi: 10.1002/jcb.29012.	`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	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`
14	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`
15	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`
16	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`
17	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`
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`

No.

Title

Href

[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

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

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

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

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

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

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

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

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

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

Polydatin enhances the chemosensitivity of osteosarcoma cells to paclitaxel. J Cell Biochem. 2019 Oct;120(10):17481-17490. doi: 10.1002/jcb.29012.

Click

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

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

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

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

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

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

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

Name	Cyclin-dependent kinase 2
UniProt ID	CDK2_HUMAN
Gene Name	CDK2
Gene ID	1017
Synonyms	CDK2, CDKN2, p33(CDK2)
Sequence	MENFQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEGVPSTAIREISLLKELNH PNIVKLLDVIHTENKLYLVFEFLHQDLKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHS HRVLHRDLKPQNLLINTEGAIKLADFGLARAFGVPVRTYTHEVVTLWYRAPEILLGCKYY STAVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDYKPSF PKWARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRISAKAALAHPFFQDVTKPVPHLRL
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	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	Corilagin, Fluorouracil
Phytochemical	Corilagin
Drug	Fluorouracil
Disease Info	[ICD-11: 2B91]	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	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	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	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	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]	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	Periplocin, Gemcitabine
Phytochemical	Periplocin
Drug	Gemcitabine
Disease Info	[ICD-11: 2C10]	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	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	Pterostilbene, Sorafenib
Phytochemical	Pterostilbene
Drug	Sorafenib
Disease Info	[ICD-11: 2B72]	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	Sulforaphane, Everolimus
Phytochemical	Sulforaphane
Drug	Everolimus
Disease Info	[ICD-11: 2C94]	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	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	Tenacissoside G, Fluorouracil
Phytochemical	Tenacissoside G
Drug	Fluorouracil
Disease Info	[ICD-11: 2B91]	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	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	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	Polyphyllin I, Palbociclib
Phytochemical	Polyphyllin I
Drug	Palbociclib
Disease Info	[ICD-11: 2C25]	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.