InterPAD - DETAILS

MPPKTPRKTAATAAAAAAEPPAPPPPPPPEEDPEQDSGPEDLPLVRLEFEETEEPDFTAL
CQKLKIPDHVRERAWLTWEKVSSVDGVLGGYIQKKKELWGICIFIAAVDLDEMSFTFTEL
QKNIEISVHKFFNLLKEIDTSTKVDNAMSRLLKKYDVLFALFSKLERTCELIYLTQPSSS
ISTEINSALVLKVSWITFLLAKGEVLQMEDDLVISFQLMLCVLDYFIKLSPPMLLKEPYK
TAVIPINGSPRTPRRGQNRSARIAKQLENDTRIIEVLCKEHECNIDEVKNVYFKNFIPFM
NSLGLVTSNGLPEVENLSKRYEEIYLKNKDLDARLFLDHDKTLQTDSIDSFETQRTPRKS
NLDEEVNVIPPHTPVRTVMNTIQQLMMILNSASDQPSENLISYFNNCTVNPKESILKRVK
DIGYIFKEKFAKAVGQGCVEIGSQRYKLGVRLYYRVMESMLKSEEERLSIQNFSKLLNDN
IFHMSLLACALEVVMATYSRSTSQNLDSGTDLSFPWILNVLNLKAFDFYKVIESFIKAEG
NLTREMIKHLERCEHRIMESLAWLSDSPLFDLIKQSKDREGPTDHLESACPLNLPLQNNH
TAADMYLSPVRSPKKKGSTTRVNSTANAETQATSAFQTQKPLKSTSLSLFYKKVYRLAYL
RLNTLCERLLSEHPELEHIIWTLFQHTLQNEYELMRDRHLDQIMMCSMYGICKVKNIDLK
FKIIVTAYKDLPHAVQETFKRVLIKEEEYDSIIVFYNSVFMQRLKTNILQYASTRPPTLS
PIPHIPRSPYKFPSSPLRIPGGNIYISPLKSPYKISEGLPTPTKMTPRSRILVSIGESFG
TSEKFQKINQMVCNSDRVLKRSAEGSNPPKPLKKLRFDIEGSDEADGSKHLPGESKFQQK
LAEMTSTRTRMQKQKMNDSMDTSNKEEK

No.	Title	Href
1	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`
2	Artesunate and cisplatin synergistically inhibit HNSCC cell growth and promote apoptosis with artesunate‑induced decreases in Rb and phosphorylated Rb levels. Oncol Rep. 2023 Aug;50(2):154. doi: 10.3892/or.2023.8591.	`Click`
3	Artesunate and cisplatin synergistically inhibit HNSCC cell growth and promote apoptosis with artesunate‑induced decreases in Rb and phosphorylated Rb levels. Oncol Rep. 2023 Aug;50(2):154. doi: 10.3892/or.2023.8591.	`Click`
4	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`
5	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`
6	Betulinic acid restores imatinib sensitivity in BCR-ABL1 kinase-independent, imatinib-resistant chronic myeloid leukemia by increasing HDAC3 ubiquitination and degradation. Ann N Y Acad Sci. 2020 May;1467(1):77-93. doi: 10.1111/nyas.14298.	`Click`
7	Halofuginone Sensitizes Lung Cancer Organoids to Cisplatin via Suppressing PI3K/AKT and MAPK Signaling Pathways. Front Cell Dev Biol. 2021 Nov 24;9:773048. doi: 10.3389/fcell.2021.773048.	`Click`
8	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`
9	Combined effect of honokiol and rosiglitazone on cell growth inhibition through enhanced G0/G1 phase arrest in hepatoma cells. J Chin Med Assoc. 2016 Aug;79(8):415-21. doi: 10.1016/j.jcma.2016.03.003.	`Click`
10	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`
11	Synergistic Effects of Nobiletin and Sorafenib Combination on Metastatic Prostate Cancer Cells. Nutr Cancer. 2019;71(8):1299-1312. doi: 10.1080/01635581.2019.1601237.	`Click`
12	Synergistic therapy with tangeretin and 5-fluorouracil accelerates the ROS/JNK mediated apoptotic pathway in human colorectal cancer cell. Food Chem Toxicol. 2020 Sep;143:111529. doi: 10.1016/j.fct.2020.111529.	`Click`
13	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`
14	The Phenolic compound Kaempferol overcomes 5-fluorouracil resistance in human resistant LS174 colon cancer cells. Sci Rep. 2019 Jan 17;9(1):195. doi: 10.1038/s41598-018-36808-z.	`Click`
15	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`
16	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

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

Artesunate and cisplatin synergistically inhibit HNSCC cell growth and promote apoptosis with artesunate‑induced decreases in Rb and phosphorylated Rb levels. Oncol Rep. 2023 Aug;50(2):154. doi: 10.3892/or.2023.8591.

Click

Artesunate and cisplatin synergistically inhibit HNSCC cell growth and promote apoptosis with artesunate‑induced decreases in Rb and phosphorylated Rb levels. Oncol Rep. 2023 Aug;50(2):154. doi: 10.3892/or.2023.8591.

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

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

Betulinic acid restores imatinib sensitivity in BCR-ABL1 kinase-independent, imatinib-resistant chronic myeloid leukemia by increasing HDAC3 ubiquitination and degradation. Ann N Y Acad Sci. 2020 May;1467(1):77-93. doi: 10.1111/nyas.14298.

Click

Halofuginone Sensitizes Lung Cancer Organoids to Cisplatin via Suppressing PI3K/AKT and MAPK Signaling Pathways. Front Cell Dev Biol. 2021 Nov 24;9:773048. doi: 10.3389/fcell.2021.773048.

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

Combined effect of honokiol and rosiglitazone on cell growth inhibition through enhanced G0/G1 phase arrest in hepatoma cells. J Chin Med Assoc. 2016 Aug;79(8):415-21. doi: 10.1016/j.jcma.2016.03.003.

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

Synergistic Effects of Nobiletin and Sorafenib Combination on Metastatic Prostate Cancer Cells. Nutr Cancer. 2019;71(8):1299-1312. doi: 10.1080/01635581.2019.1601237.

Click

Synergistic therapy with tangeretin and 5-fluorouracil accelerates the ROS/JNK mediated apoptotic pathway in human colorectal cancer cell. Food Chem Toxicol. 2020 Sep;143:111529. doi: 10.1016/j.fct.2020.111529.

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

The Phenolic compound Kaempferol overcomes 5-fluorouracil resistance in human resistant LS174 colon cancer cells. Sci Rep. 2019 Jan 17;9(1):195. doi: 10.1038/s41598-018-36808-z.

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	Retinoblastoma-associated protein
UniProt ID	RB_HUMAN
Gene Name	RB1
Gene ID	5925
Synonyms	RB1, OSRC, PPP1R130, RB, p105-Rb, p110-RB1, pRb, pp110
Sequence	MPPKTPRKTAATAAAAAAEPPAPPPPPPPEEDPEQDSGPEDLPLVRLEFEETEEPDFTAL CQKLKIPDHVRERAWLTWEKVSSVDGVLGGYIQKKKELWGICIFIAAVDLDEMSFTFTEL QKNIEISVHKFFNLLKEIDTSTKVDNAMSRLLKKYDVLFALFSKLERTCELIYLTQPSSS ISTEINSALVLKVSWITFLLAKGEVLQMEDDLVISFQLMLCVLDYFIKLSPPMLLKEPYK TAVIPINGSPRTPRRGQNRSARIAKQLENDTRIIEVLCKEHECNIDEVKNVYFKNFIPFM NSLGLVTSNGLPEVENLSKRYEEIYLKNKDLDARLFLDHDKTLQTDSIDSFETQRTPRKS NLDEEVNVIPPHTPVRTVMNTIQQLMMILNSASDQPSENLISYFNNCTVNPKESILKRVK DIGYIFKEKFAKAVGQGCVEIGSQRYKLGVRLYYRVMESMLKSEEERLSIQNFSKLLNDN IFHMSLLACALEVVMATYSRSTSQNLDSGTDLSFPWILNVLNLKAFDFYKVIESFIKAEG NLTREMIKHLERCEHRIMESLAWLSDSPLFDLIKQSKDREGPTDHLESACPLNLPLQNNH TAADMYLSPVRSPKKKGSTTRVNSTANAETQATSAFQTQKPLKSTSLSLFYKKVYRLAYL RLNTLCERLLSEHPELEHIIWTLFQHTLQNEYELMRDRHLDQIMMCSMYGICKVKNIDLK FKIIVTAYKDLPHAVQETFKRVLIKEEEYDSIIVFYNSVFMQRLKTNILQYASTRPPTLS PIPHIPRSPYKFPSSPLRIPGGNIYISPLKSPYKISEGLPTPTKMTPRSRILVSIGESFG TSEKFQKINQMVCNSDRVLKRSAEGSNPPKPLKKLRFDIEGSDEADGSKHLPGESKFQQK LAEMTSTRTRMQKQKMNDSMDTSNKEEK
Pathway Map	`MAP LINK`
T.C. Number	1.A.134.1.2; 3.A.7.1.1; 3.A.7.12.1; 3.A.7.13.1; 3.A.7.13.2; 3.A.7.2.1
KEGG ID	hsa5925
Pfam	PF00382; PF01857; PF01858; PF08934; PF11934

Pair Name	Epigallocatechin gallate, Irinotecan
Phytochemical Name	Epigallocatechin gallate
Anticancer drug Name	Irinotecan
Disease Info	[ICD-11: 2B91]	Colorectal cancer	Investigative
Regulate Info	Up-regulation	Retinoblastoma-associated protein	Phosphorylation
Result	EGCG synergizes the therapeutic effect of irinotecan through enhanced DNA damage in human colorectal cancer cells

Pair Name	Artesunate, Cisplatin
Phytochemical	Artesunate
Drug	Cisplatin
Disease Info	[ICD-11: 2C31.Z]	Head and neck squamous cell carcinoma	Investigative
Regulate Info	Down-regulation	Retinoblastoma-associated protein	Expression
Result	These results suggested that artesunate is a useful drug in combination with cisplatin.

Pair Name	Artesunate, Cisplatin
Phytochemical	Artesunate
Drug	Cisplatin
Disease Info	[ICD-11: 2C31.Z]	Head and neck squamous cell carcinoma	Investigative
Regulate Info	Down-regulation	Retinoblastoma-associated protein	Phosphorylation
Result	Artesunate and cisplatin synergistically inhibit HNSCC cell growth and promote apoptosis with artesunate‑induced decreases in Rb and phosphorylated Rb levels

Pair Name	Baicalin, Fluorouracil
Phytochemical	Baicalin
Drug	Fluorouracil
Disease Info	[ICD-11: 2B91]	Colorectal cancer	Investigative
Regulate Info	Down-regulation	Retinoblastoma-associated protein	Phosphorylation
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, Sorafenib
Phytochemical	Berbamine
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Down-regulation	Retinoblastoma-associated protein	Phosphorylation
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	Betulinic acid, Imatinib
Phytochemical	Betulinic acid
Drug	Imatinib
Disease Info	[ICD-11: 2B33.2]	Chronic myeloid leukemia	Investigative
Regulate Info	Down-regulation	Retinoblastoma-associated protein	Phosphorylation
Result	Our findings demonstrated that HDAC3 is an essential factor in BCR-ABL1 kinase-independent IM resistance, and that BA in combination with IM may be a novel treatment strategy for overcoming IM resistance in CML.

Pair Name	Halofuginone, Cisplatin
Phytochemical	Halofuginone
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Down-regulation	Retinoblastoma-associated protein	Phosphorylation
Result	Halofuginone Sensitizes Lung Cancer Organoids to Cisplatin via Suppressing PI3K/AKT and MAPK Signaling Pathways

Pair Name	Homoharringtonine, ACC010
Phytochemical	Homoharringtonine
Drug	ACC010
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia	Investigative
Regulate Info	Down-regulation	Retinoblastoma-associated protein	Phosphorylation
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	Honokiol, Rosiglitazone
Phytochemical	Honokiol
Drug	Rosiglitazone
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Down-regulation	Retinoblastoma-associated protein	Expression
Result	Honokiol combined with rosiglitazone showed more effective growth inhibition in hepatoma cells mediated through the regulation of G0/G1 phase-related proteins p21, cyclin D1, cyclin E1, and Rb and cell cycle progression

Pair Name	Nobiletin, Palbociclib
Phytochemical	Nobiletin
Drug	Palbociclib
Disease Info	[ICD-11: 2C90.0]	Renal cell carcinoma	Investigative
Regulate Info	Down-regulation	Retinoblastoma-associated protein	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	Nobiletin, Sorafenib
Phytochemical	Nobiletin
Drug	Sorafenib
Disease Info	[ICD-11: 2C82]	Prostate cancer	Investigative
Regulate Info	Up-regulation	Retinoblastoma-associated protein	Expression
Result	NOB and SOR combination was more effective than SOR and NOB alone and reduced the exposure time for SOR and NOB in PC-3 cells. Combination strategy is a therapeutic potential to improve efficacy and reduce side-effect of SOR for the treatment of metastatic prostate cancer cells.

Pair Name	Tangeretin, Fluorouracil
Phytochemical	Tangeretin
Drug	Fluorouracil
Disease Info	[ICD-11: 2B91]	Colorectal cancer	Investigative
Regulate Info	Up-regulation	Retinoblastoma-associated protein	Phosphorylation
Result	To our knowledge gained from literature, this study is the first to describe synergistic activity of TAN and 5-FU against colorectal cancer cells.

Pair Name	Zeylenone, Cisplatin
Phytochemical	Zeylenone
Drug	Cisplatin
Disease Info	[ICD-11: 2B51]	Osteosarcoma	Investigative
Regulate Info	Up-regulation	Retinoblastoma-associated protein	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	Kaempferol, Cisplatin
Phytochemical	Kaempferol
Drug	Cisplatin
Disease Info	[ICD-11: 2B90]	Colon cancer	Investigative
Regulate Info	Down-regulation	Retinoblastoma-associated protein	Phosphorylation
Result	Kaempferol overcomes 5-fluorouracil resistance in human resistant LS174 colon cancer cells

Pair Name	Norizalpinin, Imatinib
Phytochemical	Norizalpinin
Drug	Imatinib
Disease Info	[ICD-11: 2B33.4]	Leukemia	Investigative
Regulate Info	Down-regulation	Retinoblastoma-associated protein	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	Retinoblastoma-associated protein	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.