InterPAD - DETAILS

MEGAGGANDKKKISSERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVM
RLTISYLRVRKLLDAGDLDIEDDMKAQMNCFYLKALDGFVMVLTDDGDMIYISDNVNKYM
GLTQFELTGHSVFDFTHPCDHEEMREMLTHRNGLVKKGKEQNTQRSFFLRMKCTLTSRGR
TMNIKSATWKVLHCTGHIHVYDTNSNQPQCGYKKPPMTCLVLICEPIPHPSNIEIPLDSK
TFLSRHSLDMKFSYCDERITELMGYEPEELLGRSIYEYYHALDSDHLTKTHHDMFTKGQV
TTGQYRMLAKRGGYVWVETQATVIYNTKNSQPQCIVCVNYVVSGIIQHDLIFSLQQTECV
LKPVESSDMKMTQLFTKVESEDTSSLFDKLKKEPDALTLLAPAAGDTIISLDFGSNDTET
DDQQLEEVPLYNDVMLPSPNEKLQNINLAMSPLPTAETPKPLRSSADPALNQEVALKLEP
NPESLELSFTMPQIQDQTPSPSDGSTRQSSPEPNSPSEYCFYVDSDMVNEFKLELVEKLF
AEDTEAKNPFSTQDTDLDLEMLAPYIPMDDDFQLRSFDQLSPLESSSASPESASPQSTVT
VFQQTQIQEPTANATTTTATTDELKTVTKDRMEDIKILIASPSPTHIHKETTSATSSPYR
DTQSRTASPNRAGKGVIEQTEKSHPRSPNVLSVALSQRTTVPEEELNPKILALQNAQRKR
KMEHDGSLFQAVGIGTLLQQPDDHAATTSLSWKRVKGCKSSEQNGMEQKTIILIPSDLAC
RLLGQSMDESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRALDQVN

No.	Title	Href
1	Carvacrol enhances anti-tumor activity and mitigates cardiotoxicity of sorafenib in thioacetamide-induced hepatocellular carcinoma model through inhibiting TRPM7. Life Sci. 2023 Jul 1;324:121735. doi: 10.1016/j.lfs.2023.121735.	`Click`
2	Lupeol and Paclitaxel cooperate in hindering hypoxia induced vasculogenic mimicry via suppression of HIF-1α-EphA2-Laminin-5γ2 network in human oral cancer. J Cell Commun Signal. 2023 Sep;17(3):591-608. doi: 10.1007/s12079-022-00693-z.	`Click`
3	Targeting the ROS/PI3K/AKT/HIF-1α/HK2 axis of breast cancer cells: Combined administration of Polydatin and 2-Deoxy-d-glucose. J Cell Mol Med. 2019 May;23(5):3711-3723. doi: 10.1111/jcmm.14276.	`Click`
4	Apigenin Combined With Gefitinib Blocks Autophagy Flux and Induces Apoptotic Cell Death Through Inhibition of HIF-1α, c-Myc, p-EGFR, and Glucose Metabolism in EGFR L858R+T790M-Mutated H1975 Cells. Front Pharmacol. 2019 Mar 22;10:260. doi: 10.3389/fphar.2019.00260.	`Click`
5	Astaxanthin Augmented the Anti-Hepatocellular Carcinoma Efficacy of Sorafenib Through the Inhibition of the JAK2/STAT3 Signaling Pathway and Mitigation of Hypoxia within the Tumor Microenvironment. Mol Nutr Food Res. 2024 Jan;68(2):e2300569. doi: 10.1002/mnfr.202300569.	`Click`
6	Curcumenol Targeting YWHAG Inhibits the Pentose Phosphate Pathway and Enhances Antitumor Effects of Cisplatin. Evid Based Complement Alternat Med. 2022 Jun 26;2022:3988916. doi: 10.1155/2022/3988916.	`Click`
7	Targeting MTA1/HIF-1α signaling by pterostilbene in combination with histone deacetylase inhibitor attenuates prostate cancer progression. Cancer Med. 2017 Nov;6(11):2673-2685. doi: 10.1002/cam4.1209.	`Click`
8	Synergistic anti-tumour activity of sorafenib in combination with pegylated resveratrol is mediated by Akt/mTOR/p70S6k-4EBP-1 and c-Raf7MEK/ERK signaling pathways. Heliyon. 2023 Aug 19;9(8):e19154. doi: 10.1016/j.heliyon.2023.e19154.	`Click`
9	Combinatorial treatment of Rhizoma Paridis saponins and sorafenib overcomes the intolerance of sorafenib. J Steroid Biochem Mol Biol. 2018 Oct;183:159-166. doi: 10.1016/j.jsbmb.2018.06.010.	`Click`
10	Thymoquinone affects the gemcitabine sensitivity of pancreatic cancer by regulating collagen via hypoxia inducible factor-1α. Front Pharmacol. 2023 May 31;14:1138265. doi: 10.3389/fphar.2023.1138265.	`Click`
11	Ursolic acid inhibits proliferation and reverses drug resistance of ovarian cancer stem cells by downregulating ABCG2 through suppressing the expression of hypoxia-inducible factor-1α in vitro. Oncol Rep. 2016 Jul;36(1):428-40. doi: 10.3892/or.2016.4813.	`Click`
12	Combined Treatment of Tanshinone I and Epirubicin Revealed Enhanced Inhibition of Hepatocellular Carcinoma by Targeting PI3K/AKT/HIF-1α. Drug Des Devel Ther. 2022 Sep 19;16:3197-3213. doi: 10.2147/DDDT.S360691.	`Click`

No.

Title

Href

Carvacrol enhances anti-tumor activity and mitigates cardiotoxicity of sorafenib in thioacetamide-induced hepatocellular carcinoma model through inhibiting TRPM7. Life Sci. 2023 Jul 1;324:121735. doi: 10.1016/j.lfs.2023.121735.

Click

Lupeol and Paclitaxel cooperate in hindering hypoxia induced vasculogenic mimicry via suppression of HIF-1α-EphA2-Laminin-5γ2 network in human oral cancer. J Cell Commun Signal. 2023 Sep;17(3):591-608. doi: 10.1007/s12079-022-00693-z.

Click

Targeting the ROS/PI3K/AKT/HIF-1α/HK2 axis of breast cancer cells: Combined administration of Polydatin and 2-Deoxy-d-glucose. J Cell Mol Med. 2019 May;23(5):3711-3723. doi: 10.1111/jcmm.14276.

Click

Apigenin Combined With Gefitinib Blocks Autophagy Flux and Induces Apoptotic Cell Death Through Inhibition of HIF-1α, c-Myc, p-EGFR, and Glucose Metabolism in EGFR L858R+T790M-Mutated H1975 Cells. Front Pharmacol. 2019 Mar 22;10:260. doi: 10.3389/fphar.2019.00260.

Click

Astaxanthin Augmented the Anti-Hepatocellular Carcinoma Efficacy of Sorafenib Through the Inhibition of the JAK2/STAT3 Signaling Pathway and Mitigation of Hypoxia within the Tumor Microenvironment. Mol Nutr Food Res. 2024 Jan;68(2):e2300569. doi: 10.1002/mnfr.202300569.

Click

Curcumenol Targeting YWHAG Inhibits the Pentose Phosphate Pathway and Enhances Antitumor Effects of Cisplatin. Evid Based Complement Alternat Med. 2022 Jun 26;2022:3988916. doi: 10.1155/2022/3988916.

Click

Targeting MTA1/HIF-1α signaling by pterostilbene in combination with histone deacetylase inhibitor attenuates prostate cancer progression. Cancer Med. 2017 Nov;6(11):2673-2685. doi: 10.1002/cam4.1209.

Click

Synergistic anti-tumour activity of sorafenib in combination with pegylated resveratrol is mediated by Akt/mTOR/p70S6k-4EBP-1 and c-Raf7MEK/ERK signaling pathways. Heliyon. 2023 Aug 19;9(8):e19154. doi: 10.1016/j.heliyon.2023.e19154.

Click

Combinatorial treatment of Rhizoma Paridis saponins and sorafenib overcomes the intolerance of sorafenib. J Steroid Biochem Mol Biol. 2018 Oct;183:159-166. doi: 10.1016/j.jsbmb.2018.06.010.

Click

Thymoquinone affects the gemcitabine sensitivity of pancreatic cancer by regulating collagen via hypoxia inducible factor-1α. Front Pharmacol. 2023 May 31;14:1138265. doi: 10.3389/fphar.2023.1138265.

Click

Ursolic acid inhibits proliferation and reverses drug resistance of ovarian cancer stem cells by downregulating ABCG2 through suppressing the expression of hypoxia-inducible factor-1α in vitro. Oncol Rep. 2016 Jul;36(1):428-40. doi: 10.3892/or.2016.4813.

Click

Combined Treatment of Tanshinone I and Epirubicin Revealed Enhanced Inhibition of Hepatocellular Carcinoma by Targeting PI3K/AKT/HIF-1α. Drug Des Devel Ther. 2022 Sep 19;16:3197-3213. doi: 10.2147/DDDT.S360691.

Click

Name	Hypoxia-inducible factor 1-alpha
UniProt ID	HIF1A_HUMAN
Gene Name	HIF1A
Gene ID	3091
Synonyms	HIF1A, HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1, PASD8, bHLHe78
Sequence	MEGAGGANDKKKISSERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVM RLTISYLRVRKLLDAGDLDIEDDMKAQMNCFYLKALDGFVMVLTDDGDMIYISDNVNKYM GLTQFELTGHSVFDFTHPCDHEEMREMLTHRNGLVKKGKEQNTQRSFFLRMKCTLTSRGR TMNIKSATWKVLHCTGHIHVYDTNSNQPQCGYKKPPMTCLVLICEPIPHPSNIEIPLDSK TFLSRHSLDMKFSYCDERITELMGYEPEELLGRSIYEYYHALDSDHLTKTHHDMFTKGQV TTGQYRMLAKRGGYVWVETQATVIYNTKNSQPQCIVCVNYVVSGIIQHDLIFSLQQTECV LKPVESSDMKMTQLFTKVESEDTSSLFDKLKKEPDALTLLAPAAGDTIISLDFGSNDTET DDQQLEEVPLYNDVMLPSPNEKLQNINLAMSPLPTAETPKPLRSSADPALNQEVALKLEP NPESLELSFTMPQIQDQTPSPSDGSTRQSSPEPNSPSEYCFYVDSDMVNEFKLELVEKLF AEDTEAKNPFSTQDTDLDLEMLAPYIPMDDDFQLRSFDQLSPLESSSASPESASPQSTVT VFQQTQIQEPTANATTTTATTDELKTVTKDRMEDIKILIASPSPTHIHKETTSATSSPYR DTQSRTASPNRAGKGVIEQTEKSHPRSPNVLSVALSQRTTVPEEELNPKILALQNAQRKR KMEHDGSLFQAVGIGTLLQQPDDHAATTSLSWKRVKGCKSSEQNGMEQKTIILIPSDLAC RLLGQSMDESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRALDQVN
Pathway Map	`MAP LINK`
T.C. Number	8.A.92.1.4
KEGG ID	hsa3091
TTD ID	T55610
Pfam	PF00010; PF00989; PF08447; PF08448; PF08778; PF09756; PF11413; PF13426; PF14598

Pair Name	Carvacrol, Sorafenib
Phytochemical Name	Carvacrol
Anticancer drug Name	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Down-regulation	Hypoxia-inducible factor 1-alpha	Expression
Result	CARV/Sora is a promising combination for tumor suppression and overcoming Sora resistance and cardiotoxicity in HCC by modulating TRPM7. To our best knowledge, this study represents the first study to investigate the efficiency of CARV/ Sora on the HCC rat model. Moreover, no previous studies have reported the effect of inhibiting TRPM7 on HCC.

Pair Name	Lupeol, Paclitaxel
Phytochemical Name	Lupeol
Anticancer drug Name	Paclitaxel
Disease Info	[ICD-11: 2B66.0]	Oral squamous cell carcinoma	Investigative
Regulate Info	Down-regulation	Hypoxia-inducible factor 1-alpha	Expression
Result	Our findings elucidated mechanistic underpinning of hypoxia induced Laminin-5γ2 driven VM formation highlighting that Lupeol-Paclitaxel combination may serve as novel therapeutic intervention in perturbation of VM in human OSCC.

Pair Name	Polydatin, 2-Deoxy-d-glucose
Phytochemical Name	Polydatin
Anticancer drug Name	2-Deoxy-d-glucose
Disease Info	[ICD-11: 2C60]	Breast cancer	Investigative
Regulate Info	Down-regulation	Hypoxia-inducible factor 1-alpha	Expression
Result	Our study demonstrates that PD synergised with 2-DG to enhance its anti-cancer efficacy by inhibiting the ROS/PI3K/AKT/HIF-1α/HK2 signalling axis, providing a potential anti-cancer strategy.

Pair Name	Apigenin, Gefitinib
Phytochemical	Apigenin
Drug	Gefitinib
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Down-regulation	Hypoxia-inducible factor 1-alpha	Expression
Result	Apigenin Combined With Gefitinib Blocks Autophagy Flux and Induces Apoptotic Cell Death Through Inhibition of HIF-1α, c-Myc, p-EGFR, and Glucose Metabolism in EGFR L858R+T790M-Mutated H1975 Cells

Pair Name	Astaxanthin, Sorafenib
Phytochemical	Astaxanthin
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Up-regulation	Hypoxia-inducible factor 1-alpha	Expression
Result	Astaxanthin Augmented the Anti-Hepatocellular Carcinoma Efficacy of Sorafenib Through the Inhibition of the JAK2/STAT3 Signaling Pathway and Mitigation of Hypoxia within the Tumor Microenvironment

Pair Name	Curcumenol, Cisplatin
Phytochemical	Curcumenol
Drug	Cisplatin
Disease Info	[ICD-11: 2C77]	Cervical cancer	Investigative
Regulate Info	Down-regulation	Hypoxia-inducible factor 1-alpha	Expression
Result	Curcumenol can enhance cisplatin to inhibit cancer cell proliferation, migration, and invasion and promote tumor cell apoptosis. The combination of drugs may promote the apoptosis of cervical cancer cells through the YWHAG pathway.

Pair Name	Pterostilbene, Vorinostat
Phytochemical	Pterostilbene
Drug	Vorinostat
Disease Info	[ICD-11: 2C82]	Prostate cancer	Investigative
Regulate Info	Down-regulation	Hypoxia-inducible factor 1-alpha	Expression
Result	Our study provides preclinical evidence that Pter/SAHA combination treatment inhibits MTA1/HIF-1α tumor-promoting signaling in PCa. The beneficial outcome of combinatorial strategy using a natural agent and an approved drug for higher efficacy and less toxicity supports further development of MTA1-targeted therapies in PCa.

Pair Name	Resveratrol, Sorafenib
Phytochemical	Resveratrol
Drug	Sorafenib
Disease Info	[ICD-11: 2C90.0]	Renal cell carcinoma	Investigative
Regulate Info	Down-regulation	Hypoxia-inducible factor 1-alpha	Expression
Result	PEGylated resveratrol combined with sorafenib can achieve synergistic anti-RCC activity, and the mechanism may be related to the inhibition of Akt/mTOR/p70S6k-4EBP-1 and c-Raf7MEK/ERK signaling pathways.

Pair Name	Rhizoma Paridis saponins, Sorafenib
Phytochemical	Rhizoma Paridis saponins
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Down-regulation	Hypoxia-inducible factor 1-alpha	Expression
Result	All of that provided possibility to overcome the intolerance of sorafenib by drug compatibility through protection against mitochondria damage, inhibition of anaerobic glycolysis and suppression of lipid synthesis based on PI3K/Akt/mTOR pathway.

Pair Name	Thymoquinone, Gemcitabine
Phytochemical	Thymoquinone
Drug	Gemcitabine
Disease Info	[ICD-11: 2C10]	Pancreatic cancer	Investigative
Regulate Info	Down-regulation	Hypoxia-inducible factor 1-alpha	Expression
Result	TQ can promote apoptosis, inhibit migration, invasion, and metastasis, and enhance the sensitivity to GEM. The underlying mechanism may involve the regulation of ECM production through the TGFβ/Smad pathway, in which HIF-1α plays a key role.

Pair Name	Ursolic acid, Cisplatin
Phytochemical	Ursolic acid
Drug	Cisplatin
Disease Info	[ICD-11: 2C73]	Ovarian cancer	Investigative
Regulate Info	Down-regulation	Hypoxia-inducible factor 1-alpha	Expression
Result	UA inhibits the proliferation and reversal of drug resistance in ovarian CSCs by suppressing the expression of downregulation of HIF-1α and ABCG2.

Pair Name	Tanshinone I, Epirubicin
Phytochemical	Tanshinone I
Drug	Epirubicin
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Down-regulation	Hypoxia-inducible factor 1-alpha	Expression
Result	Our results suggested that Tan I could effectively improve the anti-tumor effect of EADM, and synergize EADM to reverse HIF-1α mediated resistance via targeting PI3K/AKT/HIF-1α signaling pathway.