InterPAD - DETAILS

MATSRYEPVAEIGVGAYGTVYKARDPHSGHFVALKSVRVPNGGGGGGGLPISTVREVALL
RRLEAFEHPNVVRLMDVCATSRTDREIKVTLVFEHVDQDLRTYLDKAPPPGLPAETIKDL
MRQFLRGLDFLHANCIVHRDLKPENILVTSGGTVKLADFGLARIYSYQMALTPVVVTLWY
RAPEVLLQSTYATPVDMWSVGCIFAEMFRRKPLFCGNSEADQLGKIFDLIGLPPEDDWPR
DVSLPRGAFPPRGPRPVQSVVPEMEESGAQLLLEMLTFNPHKRISAFRALQHSYLHKDEG
NPE

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	Baicalein enhances the antitumor efficacy of docetaxel on nonsmall cell lung cancer in a β-catenin-dependent manner. Phytother Res. 2020 Jan;34(1):104-117. doi: 10.1002/ptr.6501.	`Click`
3	EGCG synergizes the therapeutic effect of irinotecan through enhanced DNA damage in human colorectal cancer cells. J Cell Mol Med. 2021 Aug;25(16):7913-7921. doi: 10.1111/jcmm.16718.	`Click`
4	Acetyl-11-keto-β-boswellic acid enhances the cisplatin sensitivity of non-small cell lung cancer cells through cell cycle arrest, apoptosis induction, and autophagy suppression via p21-dependent signaling pathway. Cell Biol Toxicol. 2021 Apr;37(2):209-228. doi: 10.1007/s10565-020-09541-5.	`Click`
5	Scutellaria baicalensis enhances 5-fluorouracil-based chemotherapy via inhibition of proliferative signaling pathways. Cell Commun Signal. 2023 Jun 19;21(1):147. doi: 10.1186/s12964-023-01156-7.	`Click`
6	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`
7	Berbamine (BBM), a Natural STAT3 Inhibitor, Synergistically Enhances the Antigrowth and Proapoptotic Effects of Sorafenib on Hepatocellular Carcinoma Cells. ACS Omega. 2020 Sep 18;5(38):24838-24847. doi: 10.1021/acsomega.0c03527.	`Click`
8	Berberine and Cisplatin Exhibit Synergistic Anticancer Effects on Osteosarcoma MG-63 Cells by Inhibiting the MAPK Pathway. Molecules. 2021 Mar 17;26(6):1666. doi: 10.3390/molecules26061666.	`Click`
9	Synergistic anticancer activity of capsaicin and 3,3'-diindolylmethane in human colorectal cancer. J Agric Food Chem. 2015 May 6;63(17):4297-304. doi: 10.1021/jf506098s.	`Click`
10	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`
11	δ-Tocotrienol sensitizes and re-sensitizes ovarian cancer cells to cisplatin via induction of G1 phase cell cycle arrest and ROS/MAPK-mediated apoptosis. Cell Prolif. 2021 Nov;54(11):e13111. doi: 10.1111/cpr.13111.	`Click`
12	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`
13	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`
14	Combined Anti-Cancer Effects of Platycodin D and Sorafenib on Androgen-Independent and PTEN-Deficient Prostate Cancer. Front Oncol. 2021 May 7;11:648985. doi: 10.3389/fonc.2021.648985.	`Click`
15	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`
16	5-Fluorouracil Combined with Rutaecarpine Synergistically Suppresses the Growth of Colon Cancer Cells by Inhibiting STAT3. Drug Des Devel Ther. 2023 Mar 30;17:993-1006. doi: 10.2147/DDDT.S402824.	`Click`
17	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`
18	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`
19	Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway. Mol Med Rep. 2023 Jan;27(1):11. doi: 10.3892/mmr.2022.12898.	`Click`
20	Liquiritin induces apoptosis and autophagy in cisplatin (DDP)-resistant gastric cancer cells in vitro and xenograft nude mice in vivo. Int J Oncol. 2017 Nov;51(5):1383-1394. doi: 10.3892/ijo.2017.4134.	`Click`
21	Galangin increases the cytotoxic activity of imatinib mesylate in imatinib-sensitive and imatinib-resistant Bcr-Abl expressing leukemia cells. Cancer Lett. 2008 Jul 8;265(2):289-97. doi: 10.1016/j.canlet.2008.02.025.	`Click`
22	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

Baicalein enhances the antitumor efficacy of docetaxel on nonsmall cell lung cancer in a β-catenin-dependent manner. Phytother Res. 2020 Jan;34(1):104-117. doi: 10.1002/ptr.6501.

Click

EGCG synergizes the therapeutic effect of irinotecan through enhanced DNA damage in human colorectal cancer cells. J Cell Mol Med. 2021 Aug;25(16):7913-7921. doi: 10.1111/jcmm.16718.

Click

Acetyl-11-keto-β-boswellic acid enhances the cisplatin sensitivity of non-small cell lung cancer cells through cell cycle arrest, apoptosis induction, and autophagy suppression via p21-dependent signaling pathway. Cell Biol Toxicol. 2021 Apr;37(2):209-228. doi: 10.1007/s10565-020-09541-5.

Click

Scutellaria baicalensis enhances 5-fluorouracil-based chemotherapy via inhibition of proliferative signaling pathways. Cell Commun Signal. 2023 Jun 19;21(1):147. doi: 10.1186/s12964-023-01156-7.

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

Berbamine (BBM), a Natural STAT3 Inhibitor, Synergistically Enhances the Antigrowth and Proapoptotic Effects of Sorafenib on Hepatocellular Carcinoma Cells. ACS Omega. 2020 Sep 18;5(38):24838-24847. doi: 10.1021/acsomega.0c03527.

Click

Berberine and Cisplatin Exhibit Synergistic Anticancer Effects on Osteosarcoma MG-63 Cells by Inhibiting the MAPK Pathway. Molecules. 2021 Mar 17;26(6):1666. doi: 10.3390/molecules26061666.

Click

Synergistic anticancer activity of capsaicin and 3,3'-diindolylmethane in human colorectal cancer. J Agric Food Chem. 2015 May 6;63(17):4297-304. doi: 10.1021/jf506098s.

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

δ-Tocotrienol sensitizes and re-sensitizes ovarian cancer cells to cisplatin via induction of G1 phase cell cycle arrest and ROS/MAPK-mediated apoptosis. Cell Prolif. 2021 Nov;54(11):e13111. doi: 10.1111/cpr.13111.

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

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

Combined Anti-Cancer Effects of Platycodin D and Sorafenib on Androgen-Independent and PTEN-Deficient Prostate Cancer. Front Oncol. 2021 May 7;11:648985. doi: 10.3389/fonc.2021.648985.

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

5-Fluorouracil Combined with Rutaecarpine Synergistically Suppresses the Growth of Colon Cancer Cells by Inhibiting STAT3. Drug Des Devel Ther. 2023 Mar 30;17:993-1006. doi: 10.2147/DDDT.S402824.

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

Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway. Mol Med Rep. 2023 Jan;27(1):11. doi: 10.3892/mmr.2022.12898.

Click

Liquiritin induces apoptosis and autophagy in cisplatin (DDP)-resistant gastric cancer cells in vitro and xenograft nude mice in vivo. Int J Oncol. 2017 Nov;51(5):1383-1394. doi: 10.3892/ijo.2017.4134.

Click

Galangin increases the cytotoxic activity of imatinib mesylate in imatinib-sensitive and imatinib-resistant Bcr-Abl expressing leukemia cells. Cancer Lett. 2008 Jul 8;265(2):289-97. doi: 10.1016/j.canlet.2008.02.025.

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 4
UniProt ID	CDK4_HUMAN
Gene Name	CDK4
Gene ID	1019
Synonyms	CDK4, CMM3, PSK-J3
Sequence	MATSRYEPVAEIGVGAYGTVYKARDPHSGHFVALKSVRVPNGGGGGGGLPISTVREVALL RRLEAFEHPNVVRLMDVCATSRTDREIKVTLVFEHVDQDLRTYLDKAPPPGLPAETIKDL MRQFLRGLDFLHANCIVHRDLKPENILVTSGGTVKLADFGLARIYSYQMALTPVVVTLWY RAPEVLLQSTYATPVDMWSVGCIFAEMFRRKPLFCGNSEADQLGKIFDLIGLPPEDDWPR DVSLPRGAFPPRGPRPVQSVVPEMEESGAQLLLEMLTFNPHKRISAFRALQHSYLHKDEG NPE
Pathway Map	`MAP LINK`
KEGG ID	hsa1019
TTD ID	T85799
Pfam	PF00069; PF01636; PF03109; PF06293; 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 4	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	Baicalein, Docetaxel
Phytochemical Name	Baicalein
Anticancer drug Name	Docetaxel
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Down-regulation	Cyclin-dependent kinase 4	Expression
Result	Baicalein enhances the antitumor efficacy of docetaxel on nonsmall cell lung cancer in a β-catenin-dependent manner

Pair Name	Epigallocatechin gallate, Irinotecan
Phytochemical Name	Epigallocatechin gallate
Anticancer drug Name	Irinotecan
Disease Info	[ICD-11: 2B91]	Colorectal cancer	Investigative
Regulate Info	Down-regulation	Cyclin-dependent kinase 4	Expression
Result	EGCG synergizes the therapeutic effect of irinotecan through enhanced DNA damage in human colorectal cancer cells

Pair Name	AKBA, Cisplatin
Phytochemical	AKBA
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Down-regulation	Cyclin-dependent kinase 4	Expression
Result	Acetyl-11-keto-beta-boswellic acid enhances the cisplatin sensitivity of non-small cell lung cancer cells through cell cycle arrest, apoptosis induction, and autophagy suppression via p21-dependent signaling pathway

Pair Name	Baicalin, Fluorouracil
Phytochemical	Baicalin
Drug	Fluorouracil
Disease Info	[ICD-11: 2B91]	Colorectal cancer	Investigative
Regulate Info	Down-regulation	Cyclin-dependent kinase 4	Expression
Result	These results indicate that HQ and its component baicalin enhance the effect of 5-fluorouracil-based chemotherapy via inhibition of CDK-RB pathway. These findings may provide the rational basis for developing agents that can overcome the development of cellular drug resistance. Video Abstract.

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 4	Expression
Result	Our findings suggest that a novel combination therapy involving berbamine and ArcA could effectively eradicate glioblastoma stem-like cells.

Pair Name	Berbamine, Sorafenib
Phytochemical	Berbamine
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Down-regulation	Cyclin-dependent kinase 4	Expression
Result	These findings identify a new type of natural STAT3 inhibitor and provide a novel approach to the enhancement of SORA efficacy by blocking the activation of STAT3.

Pair Name	Berberine, Cisplatin
Phytochemical	Berberine
Drug	Cisplatin
Disease Info	[ICD-11: 2B51]	Osteosarcoma	Investigative
Regulate Info	Down-regulation	Cyclin-dependent kinase 4	Expression
Result	Berberine and Cisplatin Exhibit Synergistic Anticancer Effects on Osteosarcoma MG-63 Cells by Inhibiting the MAPK Pathway

Pair Name	Capsaicin, 3,3'-diindolylmethane
Phytochemical	Capsaicin
Drug	3,3'-diindolylmethane
Disease Info	[ICD-11: 2B90]	Colon cancer	Investigative
Regulate Info	Down-regulation	Cyclin-dependent kinase 4	Expression
Result	The present study suggests capsaicin and DIM work synergistically to inhibit cell proliferation and induce apoptosis in colorectal cancer through modulating transcriptional activity of NF-κB, p53, and target genes associated with apoptosis.

Pair Name	Daurinoline, Sorafenib
Phytochemical	Daurinoline
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Down-regulation	Cyclin-dependent kinase 4	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	Delta-Tocotrienol, Cisplatin
Phytochemical	Delta-Tocotrienol
Drug	Cisplatin
Disease Info	[ICD-11: 2C73]	Ovarian cancer	Investigative
Regulate Info	Down-regulation	Cyclin-dependent kinase 4	Expression
Result	δ-Tocotrienol sensitizes and re-sensitizes ovarian cancer cells to cisplatin via induction of G1 phase cell cycle arrest and ROS/MAPK-mediated apoptosis

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 4	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	Periplocin, Gemcitabine
Phytochemical	Periplocin
Drug	Gemcitabine
Disease Info	[ICD-11: 2C10]	Pancreatic cancer	Investigative
Regulate Info	Down-regulation	Cyclin-dependent kinase 4	Expression
Result	Periplocin exerts antitumor activity by regulating Nrf2-mediated signaling pathway in gemcitabine-resistant pancreatic cancer cells

Pair Name	Platycodin D, Sorafenib
Phytochemical	Platycodin D
Drug	Sorafenib
Disease Info	[ICD-11: 2C82]	Prostate cancer	Investigative
Regulate Info	Down-regulation	Cyclin-dependent kinase 4	Expression
Result	The combination of Platycodin D and sorafenib may exert potent anti-cancer effects specifically via FOXO3a

Pair Name	Pterostilbene, Sorafenib
Phytochemical	Pterostilbene
Drug	Sorafenib
Disease Info	[ICD-11: 2B72]	Gastric cancer	Investigative
Regulate Info	Down-regulation	Cyclin-dependent kinase 4	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	Rutaecarpine, Fluorouracil
Phytochemical	Rutaecarpine
Drug	Fluorouracil
Disease Info	[ICD-11: 2B91]	Colorectal cancer	Investigative
Regulate Info	Down-regulation	Cyclin-dependent kinase 4	Expression
Result	Combined therapy with 5-FU and RUT exerted a superior curative effect in CRC than treatment with either single drug alone and has potential as a novel therapeutic modality for the treatment of CRC.

Pair Name	Tangeretin, Metformin
Phytochemical	Tangeretin
Drug	Metformin
Disease Info	[ICD-11: 2C60]	Breast cancer	Investigative
Regulate Info	Down-regulation	Cyclin-dependent kinase 4	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 4	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	Ursolic acid, Doxorubicin
Phytochemical	Ursolic acid
Drug	Doxorubicin
Disease Info	[ICD-11: 2B91]	Colorectal cancer	Investigative
Regulate Info	Down-regulation	Cyclin-dependent kinase 4	Expression
Result	UA may be a novel anticancer strategy and could be considered for investigation as a complementary chemotherapy agent in the future.

Pair Name	Liquiritin, Cisplatin
Phytochemical	Liquiritin
Drug	Cisplatin
Disease Info	[ICD-11: 2B72]	Gastric cancer	Investigative
Regulate Info	Down-regulation	Cyclin-dependent kinase 4	Expression
Result	Liquiritin induces apoptosis and autophagy in cisplatin (DDP)-resistant gastric cancer cells in vitro and xenograft nude mice in vivo

Pair Name	Norizalpinin, Imatinib
Phytochemical	Norizalpinin
Drug	Imatinib
Disease Info	[ICD-11: 2B33.4]	Leukemia	Investigative
Regulate Info	Down-regulation	Cyclin-dependent kinase 4	Expression
Result	Galangin increases the cytotoxic activity of imatinib mesylate in imatinib-sensitive and imatinib-resistant Bcr-Abl expressing leukemia cells

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 4	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.