InterPAD - DETAILS

MSGRPRTTSFAESCKPVQQPSAFGSMKVSRDKDGSKVTTVVATPGQGPDRPQEVSYTDTK
VIGNGSFGVVYQAKLCDSGELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFYSSG
EKKDEVYLNLVLDYVPETVYRVARHYSRAKQTLPVIYVKLYMYQLFRSLAYIHSFGICHR
DIKPQNLLLDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSSIDV
WSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIKAHP
WTKVFRPRTPPEAIALCSRLLEYTPTARLTPLEACAHSFFDELRDPNVKLPNGRDTPALF
NFTTQELSSNPPLATILIPPHARIQAAASTPTNATAASDANTGDRGQTNNAASASASNST

No.	Title	Href
1	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`
2	Carnosic acid nanocluster-based framework combined with PD-1 inhibitors impeded tumorigenesis and enhanced immunotherapy in hepatocellular carcinoma. Funct Integr Genomics. 2024 Jan 6;24(1):5. doi: 10.1007/s10142-024-01286-2.	`Click`
3	Combined Application of Salinomycin and ATRA Induces Apoptosis and Differentiation of Acute Myeloid Leukemia Cells by Inhibiting WNT/β-Catenin Pathway. Anticancer Agents Med Chem. 2023;23(9):1074-1084. doi: 10.2174/1871520623666230110121629.	`Click`
4	β-Sitosterol and Gemcitabine Exhibit Synergistic Anti-Pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial-Mesenchymal Transition by Deactivating Akt/GSK-3β Signaling. Front Pharmacol. 2020 Nov 20;11:565535. doi: 10.3389/fphar.2020.565535.	`Click`
5	Our data indicate that BMDC has the potential to improve the treatment of primary EGFR-TKI resistant NISCLC that cannot be controlled with single-target agent, such as icotinib.	`Click`
6	Effects of low-dose bufalin combined with hydroxycamptothecin on human castration-resistant prostate cancer xenografts in nude mice. Exp Ther Med. 2021 Sep;22(3):1015. doi: 10.3892/etm.2021.10447.	`Click`
7	Costunolide is a dual inhibitor of MEK1 and AKT1/2 that overcomes osimertinib resistance in lung cancer. Mol Cancer. 2022;21(1):193. Published 2022 Oct 6. doi:10.1186/s12943-022-01662-1	`Click`
8	Potentiation of TRAIL-Induced Apoptosis in TRAIL-Resistant Cholangiocarcinoma Cells by Curcumin through the Induction of DR5 Membrane Localization and Disruption of the Anti-Apoptotic Complex DR5/DDX3/GSK3β. Asian Pac J Cancer Prev. 2023 Feb 1;24(2):425-434. doi: 10.31557/APJCP.2023.24.2.425.	`Click`
9	Dihydroartemisinin inhibits the development of colorectal cancer by GSK-3β/TCF7/MMP9 pathway and synergies with capecitabine. Cancer Lett. 2024 Feb 1;582:216596. doi: 10.1016/j.canlet.2023.216596.	`Click`
10	Luteolin and Gemcitabine Protect Against Pancreatic Cancer in an Orthotopic Mouse Model. Pancreas. 2015 Jan;44(1):144-51. doi: 10.1097/MPA.0000000000000215.	`Click`
11	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`
12	Oxidized tea polyphenol (OTP-3) targets EGFR synergistic nimotuzumab at inhibition of non-small cell lung tumor growth. Bioorg Chem. 2022 Nov;128:106084. doi: 10.1016/j.bioorg.2022.106084.	`Click`
13	Platycodin D induces apoptotic cell death through PI3K/AKT and MAPK/ERK pathways and synergizes with venetoclax in acute myeloid leukemia. Eur J Pharmacol. 2023 Oct 5;956:175957. doi: 10.1016/j.ejphar.2023.175957.	`Click`
14	Gemcitabine potentiates anti-tumor effect of resveratrol on pancreatic cancer via down-regulation of VEGF-B. J Cancer Res Clin Oncol. 2021 Jan;147(1):93-103. doi: 10.1007/s00432-020-03384-7.	`Click`
15	Synergistic effect of toosendanin and regorafenib against cell proliferation and migration by regulating WWOX signaling pathway in hepatocellular carcinoma. Phytother Res. 2021 Aug;35(8):4567-4578. doi: 10.1002/ptr.7174.	`Click`
16	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`
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	Enhanced anticancer activity by the combination of vinpocetine and sorafenib via PI3K/AKT/GSK-3β signaling axis in hepatocellular carcinoma cells. Anticancer Drugs. 2021 Aug 1;32(7):727-733. doi: 10.1097/CAD.0000000000001056.	`Click`

No.

Title

Href

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

Carnosic acid nanocluster-based framework combined with PD-1 inhibitors impeded tumorigenesis and enhanced immunotherapy in hepatocellular carcinoma. Funct Integr Genomics. 2024 Jan 6;24(1):5. doi: 10.1007/s10142-024-01286-2.

Click

Combined Application of Salinomycin and ATRA Induces Apoptosis and Differentiation of Acute Myeloid Leukemia Cells by Inhibiting WNT/β-Catenin Pathway. Anticancer Agents Med Chem. 2023;23(9):1074-1084. doi: 10.2174/1871520623666230110121629.

Click

β-Sitosterol and Gemcitabine Exhibit Synergistic Anti-Pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial-Mesenchymal Transition by Deactivating Akt/GSK-3β Signaling. Front Pharmacol. 2020 Nov 20;11:565535. doi: 10.3389/fphar.2020.565535.

Click

Our data indicate that BMDC has the potential to improve the treatment of primary EGFR-TKI resistant NISCLC that cannot be controlled with single-target agent, such as icotinib.

Click

Effects of low-dose bufalin combined with hydroxycamptothecin on human castration-resistant prostate cancer xenografts in nude mice. Exp Ther Med. 2021 Sep;22(3):1015. doi: 10.3892/etm.2021.10447.

Click

Costunolide is a dual inhibitor of MEK1 and AKT1/2 that overcomes osimertinib resistance in lung cancer. Mol Cancer. 2022;21(1):193. Published 2022 Oct 6. doi:10.1186/s12943-022-01662-1

Click

Potentiation of TRAIL-Induced Apoptosis in TRAIL-Resistant Cholangiocarcinoma Cells by Curcumin through the Induction of DR5 Membrane Localization and Disruption of the Anti-Apoptotic Complex DR5/DDX3/GSK3β. Asian Pac J Cancer Prev. 2023 Feb 1;24(2):425-434. doi: 10.31557/APJCP.2023.24.2.425.

Click

Dihydroartemisinin inhibits the development of colorectal cancer by GSK-3β/TCF7/MMP9 pathway and synergies with capecitabine. Cancer Lett. 2024 Feb 1;582:216596. doi: 10.1016/j.canlet.2023.216596.

Click

Luteolin and Gemcitabine Protect Against Pancreatic Cancer in an Orthotopic Mouse Model. Pancreas. 2015 Jan;44(1):144-51. doi: 10.1097/MPA.0000000000000215.

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

Oxidized tea polyphenol (OTP-3) targets EGFR synergistic nimotuzumab at inhibition of non-small cell lung tumor growth. Bioorg Chem. 2022 Nov;128:106084. doi: 10.1016/j.bioorg.2022.106084.

Click

Platycodin D induces apoptotic cell death through PI3K/AKT and MAPK/ERK pathways and synergizes with venetoclax in acute myeloid leukemia. Eur J Pharmacol. 2023 Oct 5;956:175957. doi: 10.1016/j.ejphar.2023.175957.

Click

Gemcitabine potentiates anti-tumor effect of resveratrol on pancreatic cancer via down-regulation of VEGF-B. J Cancer Res Clin Oncol. 2021 Jan;147(1):93-103. doi: 10.1007/s00432-020-03384-7.

Click

Synergistic effect of toosendanin and regorafenib against cell proliferation and migration by regulating WWOX signaling pathway in hepatocellular carcinoma. Phytother Res. 2021 Aug;35(8):4567-4578. doi: 10.1002/ptr.7174.

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

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

Enhanced anticancer activity by the combination of vinpocetine and sorafenib via PI3K/AKT/GSK-3β signaling axis in hepatocellular carcinoma cells. Anticancer Drugs. 2021 Aug 1;32(7):727-733. doi: 10.1097/CAD.0000000000001056.

Click

Name	Glycogen synthase kinase-3 beta
UniProt ID	GSK3B_HUMAN
Gene Name	GSK3B
Gene ID	2932
Synonyms	GSK3B
Sequence	MSGRPRTTSFAESCKPVQQPSAFGSMKVSRDKDGSKVTTVVATPGQGPDRPQEVSYTDTK VIGNGSFGVVYQAKLCDSGELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFYSSG EKKDEVYLNLVLDYVPETVYRVARHYSRAKQTLPVIYVKLYMYQLFRSLAYIHSFGICHR DIKPQNLLLDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSSIDV WSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIKAHP WTKVFRPRTPPEAIALCSRLLEYTPTARLTPLEACAHSFFDELRDPNVKLPNGRDTPALF NFTTQELSSNPPLATILIPPHARIQAAASTPTNATAASDANTGDRGQTNNAASASASNST
Pathway Map	`MAP LINK`
T.C. Number	8.A.160.2.1
KEGG ID	hsa2932
TTD ID	T70977
Pfam	PF00069; PF01633; PF01636; PF03109; PF06293; PF07714; PF14531

Pair Name	Baicalein, Docetaxel
Phytochemical Name	Baicalein
Anticancer drug Name	Docetaxel
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Up-regulation	Glycogen synthase kinase-3 beta	Phosphorylation
Result	Baicalein enhances the antitumor efficacy of docetaxel on nonsmall cell lung cancer in a β-catenin-dependent manner

Pair Name	Carnosic acid, Anti-PD-1 antibody
Phytochemical Name	Carnosic acid
Anticancer drug Name	Anti-PD-1 antibody
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Down-regulation	Glycogen synthase kinase-3 beta	Expression
Result	CA-NBF combined with anti-PD-1 have stronger immunomodulatory and anticancer effects without increasing biological toxicity.

Pair Name	All-trans retinoic acid, Salinomycin
Phytochemical	All-trans-retinoic acid
Drug	Salinomycin
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia	Investigative
Regulate Info	Down-regulation	Glycogen synthase kinase-3 beta	Phosphorylation
Result	S+RA induced differentiation by β-catenin-inhibition-mediated up-regulation of C/EBPs and PU.1 and suppression of c-Myc. S+RA triggered apoptosis through β-catenin-inhibition-regulated ΔΨm collapse and caspase-3/7 activation. Taken together, our findings may provide novel therapeutic strategies for AML patients by targeting the WNT/β-catenin pathway.

Pair Name	Beta-Sitosterol, Gemcitabine
Phytochemical	Beta-Sitosterol
Drug	Gemcitabine
Disease Info	[ICD-11: 2C10]	Pancreatic cancer	Investigative
Regulate Info	Down-regulation	Glycogen synthase kinase-3 beta	Phosphorylation
Result	β-Sitosterol and Gemcitabine Exhibit Synergistic Anti-pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial-Mesenchymal Transition by Deactivating Akt/GSK-3β Signaling

Pair Name	Bisdemethoxycucurmin, Icotinib
Phytochemical	Bisdemethoxycucurmin
Drug	Icotinib
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Up-regulation	Glycogen synthase kinase-3 beta	Expression
Result	Our data indicate that BMDC has the potential to improve the treatment of primary EGFR-TKI resistant NISCLC that cannot be controlled with single-target agent, such as icotinib.

Pair Name	Bufalin, Hydroxycamptothecin
Phytochemical	Bufalin
Drug	Hydroxycamptothecin
Disease Info	[ICD-11: 2C82]	Prostate cancer	Investigative
Regulate Info	Up-regulation	Glycogen synthase kinase-3 beta	Expression
Result	The present study suggested that the combination of bufalin and hydroxycampothecin improved the inhibitory effects of both drugs on CRPC tumors in vivo, potentially via the regulation of the PI3K/AKT/GSK-3β and p53-dependent apoptosis signaling pathways.

Pair Name	Costunolide, Osimertinib
Phytochemical	Costunolide
Drug	Osimertinib
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Down-regulation	Glycogen synthase kinase-3 beta	Phosphorylation
Result	The combination of osimertinib and costunolide showed synergistic or additive inhibitory effects on tumor growth in osimertinib-resistant cell lines and PDX model. Hence, this study highlights a potential therapeutic strategy for osimertinib-resistant patients through targeting of MEK1 and AKT1/2 by costunolide.

Pair Name	Curcumin, TNF-related apoptosis inducing ligand
Phytochemical	Curcumin
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C17]	Hepatocellular carcinoma	Investigative
Regulate Info	Down-regulation	Glycogen synthase kinase-3 beta	Expression
Result	The present study demonstrates the potential of using curcumin in combination with TRAIL to yield better TRAIL therapy outcomes in TRAIL-resistant CCA.

Pair Name	Dihydroartemisinin, Capecitabine
Phytochemical	Dihydroartemisinin
Drug	Capecitabine
Disease Info	[ICD-11: 2B91]	Colorectal cancer	Investigative
Regulate Info	Down-regulation	Glycogen synthase kinase-3 beta	Expression
Result	DHA in combination with Cap could be a novel therapeutic strategy for CRC with improved efficacy and reduced side effects.

Pair Name	Luteolin, Gemcitabine
Phytochemical	Luteolin
Drug	Gemcitabine
Disease Info	[ICD-11: 2C10.0]	Pancreatic ductal adenocarcinoma	Investigative
Regulate Info	Down-regulation	Glycogen synthase kinase-3 beta	Expression
Result	Luteolin + Gem promoted apoptotic cell death in pancreatic tumor cells in vivo through inhibition of the K-ras/GSK-3β/NF-κB signaling pathway, leading to a reduction in the Bcl-2/Bax ratio, release of cytochrome c, and activation of caspase 3.

Pair Name	Oridonin, Venetoclax
Phytochemical	Oridonin
Drug	Venetoclax
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia	Investigative
Regulate Info	Down-regulation	Glycogen synthase kinase-3 beta	Phosphorylation
Result	Oridonin and venetoclax synergistically promote AML cell apoptosis by inhibiting AKT signaling.

Pair Name	Oxidized tea polyphenol, Nimotuzumab
Phytochemical	Oxidized tea polyphenol
Drug	Nimotuzumab
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Down-regulation	Glycogen synthase kinase-3 beta	Phosphorylation
Result	OTP-3 can also serve as an effective therapeutic agent in NSCLC where it can augment the effects of nimotuzumab, a valuable property for combination agents.

Pair Name	Platycodin D, Venetoclax
Phytochemical	Platycodin D
Drug	Venetoclax
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia	Investigative
Regulate Info	Down-regulation	Glycogen synthase kinase-3 beta	Phosphorylation
Result	Platycodin D may be a potent therapeutic candidate for the treatment of AML

Pair Name	Resveratrol, Gemcitabine
Phytochemical	Resveratrol
Drug	Gemcitabine
Disease Info	[ICD-11: 2C10]	Pancreatic cancer	Investigative
Regulate Info	Up-regulation	Glycogen synthase kinase-3 beta	Phosphorylation
Result	These results suggest that VEGF-B signaling pathway plays an important role in the development of PaCa and combination of GEM and RSV would be a promising modality for clinical PaCa therapy.

Pair Name	Toosendanin, Regorafenib
Phytochemical	Toosendanin
Drug	Regorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Up-regulation	Glycogen synthase kinase-3 beta	Phosphorylation
Result	TSN and RGF combination (TRC) synergistically inhibited the proliferation and migration of MHCC-97L cells. The upregulation of WWOX (WW-domain containing oxidoreductase) played a vital role in the HCC cell growth treated with TRC

Pair Name	Ursolic acid, Doxorubicin
Phytochemical	Ursolic acid
Drug	Doxorubicin
Disease Info	[ICD-11: 2B91]	Colorectal cancer	Investigative
Regulate Info	Down-regulation	Glycogen synthase kinase-3 beta	Phosphorylation
Result	UA may be a novel anticancer strategy and could be considered for investigation as a complementary chemotherapy agent in the future.

Pair Name	Zeylenone, Cisplatin
Phytochemical	Zeylenone
Drug	Cisplatin
Disease Info	[ICD-11: 2B51]	Osteosarcoma	Investigative
Regulate Info	Down-regulation	Glycogen synthase kinase-3 beta	Phosphorylation
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	Vinpocetine, Sorafenib
Phytochemical	Vinpocetine
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Up-regulation	Glycogen synthase kinase-3 beta	Activity
Result	Vinpocetine may be a potential candidate for sorafenib sensitization and HCC treatment, and our results may help to elucidate more effective therapeutic options for HCC patients with sorafenib resistance.