InterPAD - DETAILS

Bortezomib, 179324-69-7, Velcade, PS-341, Bortezomib (PS-341), LDP-341, Ps 341, Bortezomib accord, ((R)-3-Methyl-1-((S)-3-phenyl-2-(pyrazine-2-carboxamido)propanamido)butyl)boronic acid, [(1R)-3-methyl-1-[[(2S)-3-phenyl-2-(pyrazine-2-carbonylamino)propanoyl]amino]butyl]boronic acid, NSC-681239, Boronic acid, B-[(1R)-3-methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(2-pyrazinylcarbonyl)amino]propyl]amino]butyl]-, C19H25BN4O4, Peptide boronate, MLN-341, PS 341 (pharmaceutical), UNII-69G8BD63PP, 69G8BD63PP, Bortezomib (Velcade), N-[(1R)-1-(DIHYDROXYBORYL)-3-METHYLBUTYL]-N-(PYRAZIN-2-YLCARBONYL)-L-PHENYLALANINAMIDE, DTXSID3040980, CHEBI:52717, HSDB 7666, MG 341, MG-341, NSC 681239, CHEMBL325041, DTXCID1020980, MFCD09056737, NSC681239, NCGC00242506-02, S1013, BORTEZOMIB (MART.), BORTEZOMIB [MART.], N-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-Nalpha-(pyrazin-2-ylcarbonyl)-L-phenylalaninamide, N-((1S)-1-Benzyl-2-(((1R)-1-(dihydroxyboranyl)-3-methylbutyl)amino)-2-oxoethyl)pyrazinecarboxamide, radiciol, Pyz-Phe-boroLeu, (R)-3-methyl-1-((S)-3-phenyl-2-(pyrazine-2-carboxamido)propanamido)butylboronic acid, [(1R)-3-methyl-1-({(2S)-3-phenyl-2-[(pyrazin-2-ylcarbonyl)amino]propanoyl}amino)butyl]boronic acid, Boronic acid, ((1R)-3-methyl-1-(((2S)-1-oxo-3-phenyl-2-((pyrazinylcarbonyl)amino)propyl)amino)butyl)-, N-((1S)-1-benzyl-2-(((1R)-1-(dihydroxyboranyl)-3-methylbutyl)amino)2-oxoethylpyrazinecarboxamide, Velcade (TN), DPBA, CAS-179324-69-7, LDP 341, [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic acid, bortezomibum, Bortexomib, PROSCRIPT BORONIC ACID, Bortezomib [USAN:INN:BAN], Bortezomib hydrate, Bortezomib,Velcade, LPD 341, LPD-341, N-((1R)-1-(DIHYDROXYBORYL)-3-methylbutyl)-N-(pyrazin-2-ylcarbonyl)-L-phenylalaninamide, NCGC00168751-01, NCGC00181022-01, ((1R)-3-Methyl-1-(((2S)-3-phenyl-2-((pyrazinylcarbonyl)amino)propanoyl)amino)butyl)boronic acid, [(1R)-3-Methyl-1-[[(2S)-3-phenyl-2-[(pyrazinylcarbonyl)amino]propanoyl]amino]butyl]boronic acid, N-((1R)-1-(dihydroxyboranyl)-3-methylbutyl)-N(alpha)-(pyrazin-2-ylcarbonyl)-L-phenylalaninamide, N-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-N(alpha)-(pyrazin-2-ylcarbonyl)-L-phenylalaninamide, Bortezomib- Bio-X, Bortezomib [USAN], Velcade (Millenium), 3mg0, BORTEZOMIB [MI], Bortezomib for Injection, BORTEZOMIB [INN], BORTEZOMIB [JAN], BORTEZOMIB [HSDB], PS-341 [Bortezomib], BORTEZOMIB [VANDF], BORTEZOMIB [WHO-DD], MLS004774142, Bortezomib (JAN/USAN/INN), BORTEZOMIB [EMA EPAR], SCHEMBL192129, GTPL6391, BORTEZOMIB [ORANGE BOOK], BORTEZOMIB HYDRATE [JAN], L01XX32, EX-A8373, Tox21_112630, Tox21_112672, BDBM50069989, HB4036, NSC756655, AKOS015909706, Tox21_112672_1, AM81235, CCG-268449, CS-1039, DB00188, NSC-756655, NCGC00242506-01, NCGC00242506-06, NCGC00242506-07, AS-15721, BB164258, HY-10227, NCI60_029010, SMR003500787, Bortezomib (Velcade,MG-341,PS-341)?, B5741, NS00006197, SW208077-3, A18332, D03150, EN300-657180, AB01273951-01, AB01273951-02, AB01273951_03, Q419319, SR-01000939863, SR-01000939863-2, BRD-K88510285-001-02-0, Z2213886907, ((R)-3-methyl-1-((S)-3-phenyl-2-(pyrazine-2-carboxamido)propanamido)butyl)boronicacid, (R)-3-methyl-1-((S)-3-phenyl-2-(pyrazine-6-carboxamido)propanamido)butylboronic acid, [(1R)-3-methyl-1-[(2S)-3-phenyl-2-[(pyrazin-2-yl)formamido]propanamido]butyl]boronic acid, (1R)-3-Methyl-1-({(2S)-3-phenyl-2-[(2-pyrazinylcarbonyl)amino]propanoyl}amino)butylboronic acid, AldrichCPR, (R)-3-METHYL-1-((S)-3-PHENYL-2-(PYRAZINE-2-CARBOXAMIDO)PROPANAMIDO)BUTAN-2-YLBORONIC ACID, [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]-butyl]boronic acid, 1610526-91-4, Boronic acid, (3-methyl-1-((1-oxo-3-phenyl-2-((pyrazinylcarbonyl)amino)propyl)amino)butyl)-, (S-(R*,S*))-, Boronic acid, [(1(R)-3-methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]-, Radiciol , NSC 681239 , MG 341 , DPBA , Brotezamide , LDP 341

No.	Title	Href
1	Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors. Blood. 2009;113(23):5927-5937. doi:10.1182/blood-2008-07-171389	`Click`
2	Ursodeoxycholic Acid Inhibits Glioblastoma Progression via Endoplasmic Reticulum Stress Related Apoptosis and Synergizes with the Proteasome Inhibitor Bortezomib. ACS Chem Neurosci. 2020 May 6;11(9):1337-1346. doi: 10.1021/acschemneuro.0c00095.	`Click`
3	Thymoquinone overcomes chemoresistance and enhances the anticancer effects of bortezomib through abrogation of NF-κB regulated gene products in multiple myeloma xenograft mouse model. Oncotarget. 2014 Feb 15;5(3):634-48. doi: 10.18632/oncotarget.1596.	`Click`
4	Solamargine induces autophagy-mediated apoptosis and enhances bortezomib activity in multiple myeloma. Clin Exp Pharmacol Physiol. 2022 Jun;49(6):674-685. doi: 10.1111/1440-1681.13643.	`Click`
5	Sanguinarine Induces Apoptosis Pathway in Multiple Myeloma Cell Lines via Inhibition of the JaK2/STAT3 Signaling. Front Oncol. 2019 Apr 17;9:285. doi: 10.3389/fonc.2019.00285.	`Click`
6	Piperlongumine and bortezomib synergically inhibit cholangiocarcinoma via ER stress-induced cell death. Naunyn Schmiedebergs Arch Pharmacol. 2023 Jan;396(1):109-120. doi: 10.1007/s00210-022-02305-4.	`Click`
7	Lycorine Downregulates HMGB1 to Inhibit Autophagy and Enhances Bortezomib Activity in Multiple Myeloma. Theranostics. 2016 Sep 24;6(12):2209-2224. doi: 10.7150/thno.15584.	`Click`
8	Luteolin inhibits the TGF-β signaling pathway to overcome bortezomib resistance in multiple myeloma. Cancer Lett. 2023 Feb 1;554:216019. doi: 10.1016/j.canlet.2022.216019.	`Click`
9	Flavokawain B targets protein neddylation for enhancing the anti-prostate cancer effect of Bortezomib via Skp2 degradation. Cell Commun Signal. 2019 Mar 18;17(1):25. doi: 10.1186/s12964-019-0338-2.	`Click`
10	α-Tocotrienol and Redox-Silent Analogs of Vitamin E Enhances Bortezomib Sensitivity in Solid Cancer Cells through Modulation of NFE2L1. Int J Mol Sci. 2023 May 27;24(11):9382. doi: 10.3390/ijms24119382.	`Click`
11	An in vitro and in vivo investigation of the cytotoxic effects of caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester and bortezomib in multiple myeloma cells. Turk J Med Sci. 2015;45(1):38-46. doi: 10.3906/sag-1401-127.	`Click`
12	Elemene sensitizes pancreatic cancer cells to bortezomib by enhancing proteasome inhibition via molecular patch mechanism. Signal Transduct Target Ther. 2023 Feb 27;8(1):87. doi: 10.1038/s41392-023-01373-z.	`Click`
13	Combined therapeutic effects of bortezomib and anacardic acid on multiple myeloma cells via activation of the endoplasmic reticulum stress response. Mol Med Rep. 2016 Sep;14(3):2679-84. doi: 10.3892/mmr.2016.5533.	`Click`

No.

Title

Href

Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors. Blood. 2009;113(23):5927-5937. doi:10.1182/blood-2008-07-171389

Click

Ursodeoxycholic Acid Inhibits Glioblastoma Progression via Endoplasmic Reticulum Stress Related Apoptosis and Synergizes with the Proteasome Inhibitor Bortezomib. ACS Chem Neurosci. 2020 May 6;11(9):1337-1346. doi: 10.1021/acschemneuro.0c00095.

Click

Thymoquinone overcomes chemoresistance and enhances the anticancer effects of bortezomib through abrogation of NF-κB regulated gene products in multiple myeloma xenograft mouse model. Oncotarget. 2014 Feb 15;5(3):634-48. doi: 10.18632/oncotarget.1596.

Click

Solamargine induces autophagy-mediated apoptosis and enhances bortezomib activity in multiple myeloma. Clin Exp Pharmacol Physiol. 2022 Jun;49(6):674-685. doi: 10.1111/1440-1681.13643.

Click

Sanguinarine Induces Apoptosis Pathway in Multiple Myeloma Cell Lines via Inhibition of the JaK2/STAT3 Signaling. Front Oncol. 2019 Apr 17;9:285. doi: 10.3389/fonc.2019.00285.

Click

Piperlongumine and bortezomib synergically inhibit cholangiocarcinoma via ER stress-induced cell death. Naunyn Schmiedebergs Arch Pharmacol. 2023 Jan;396(1):109-120. doi: 10.1007/s00210-022-02305-4.

Click

Lycorine Downregulates HMGB1 to Inhibit Autophagy and Enhances Bortezomib Activity in Multiple Myeloma. Theranostics. 2016 Sep 24;6(12):2209-2224. doi: 10.7150/thno.15584.

Click

Luteolin inhibits the TGF-β signaling pathway to overcome bortezomib resistance in multiple myeloma. Cancer Lett. 2023 Feb 1;554:216019. doi: 10.1016/j.canlet.2022.216019.

Click

Flavokawain B targets protein neddylation for enhancing the anti-prostate cancer effect of Bortezomib via Skp2 degradation. Cell Commun Signal. 2019 Mar 18;17(1):25. doi: 10.1186/s12964-019-0338-2.

Click

α-Tocotrienol and Redox-Silent Analogs of Vitamin E Enhances Bortezomib Sensitivity in Solid Cancer Cells through Modulation of NFE2L1. Int J Mol Sci. 2023 May 27;24(11):9382. doi: 10.3390/ijms24119382.

Click

An in vitro and in vivo investigation of the cytotoxic effects of caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester and bortezomib in multiple myeloma cells. Turk J Med Sci. 2015;45(1):38-46. doi: 10.3906/sag-1401-127.

Click

Elemene sensitizes pancreatic cancer cells to bortezomib by enhancing proteasome inhibition via molecular patch mechanism. Signal Transduct Target Ther. 2023 Feb 27;8(1):87. doi: 10.1038/s41392-023-01373-z.

Click

Combined therapeutic effects of bortezomib and anacardic acid on multiple myeloma cells via activation of the endoplasmic reticulum stress response. Mol Med Rep. 2016 Sep;14(3):2679-84. doi: 10.3892/mmr.2016.5533.

Click

Name	Bortezomib
PubChem CID	387447
Molecular Weight	384.2g/mol
Synonyms	Bortezomib, 179324-69-7, Velcade, PS-341, Bortezomib (PS-341), LDP-341, Ps 341, Bortezomib accord, ((R)-3-Methyl-1-((S)-3-phenyl-2-(pyrazine-2-carboxamido)propanamido)butyl)boronic acid, [(1R)-3-methyl-1-[[(2S)-3-phenyl-2-(pyrazine-2-carbonylamino)propanoyl]amino]butyl]boronic acid, NSC-681239, Boronic acid, B-[(1R)-3-methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(2-pyrazinylcarbonyl)amino]propyl]amino]butyl]-, C19H25BN4O4, Peptide boronate, MLN-341, PS 341 (pharmaceutical), UNII-69G8BD63PP, 69G8BD63PP, Bortezomib (Velcade), N-[(1R)-1-(DIHYDROXYBORYL)-3-METHYLBUTYL]-N-(PYRAZIN-2-YLCARBONYL)-L-PHENYLALANINAMIDE, DTXSID3040980, CHEBI:52717, HSDB 7666, MG 341, MG-341, NSC 681239, CHEMBL325041, DTXCID1020980, MFCD09056737, NSC681239, NCGC00242506-02, S1013, BORTEZOMIB (MART.), BORTEZOMIB [MART.], N-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-Nalpha-(pyrazin-2-ylcarbonyl)-L-phenylalaninamide, N-((1S)-1-Benzyl-2-(((1R)-1-(dihydroxyboranyl)-3-methylbutyl)amino)-2-oxoethyl)pyrazinecarboxamide, radiciol, Pyz-Phe-boroLeu, (R)-3-methyl-1-((S)-3-phenyl-2-(pyrazine-2-carboxamido)propanamido)butylboronic acid, [(1R)-3-methyl-1-({(2S)-3-phenyl-2-[(pyrazin-2-ylcarbonyl)amino]propanoyl}amino)butyl]boronic acid, Boronic acid, ((1R)-3-methyl-1-(((2S)-1-oxo-3-phenyl-2-((pyrazinylcarbonyl)amino)propyl)amino)butyl)-, N-((1S)-1-benzyl-2-(((1R)-1-(dihydroxyboranyl)-3-methylbutyl)amino)2-oxoethylpyrazinecarboxamide, Velcade (TN), DPBA, CAS-179324-69-7, LDP 341, [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic acid, bortezomibum, Bortexomib, PROSCRIPT BORONIC ACID, Bortezomib [USAN:INN:BAN], Bortezomib hydrate, Bortezomib,Velcade, LPD 341, LPD-341, N-((1R)-1-(DIHYDROXYBORYL)-3-methylbutyl)-N-(pyrazin-2-ylcarbonyl)-L-phenylalaninamide, NCGC00168751-01, NCGC00181022-01, ((1R)-3-Methyl-1-(((2S)-3-phenyl-2-((pyrazinylcarbonyl)amino)propanoyl)amino)butyl)boronic acid, [(1R)-3-Methyl-1-[[(2S)-3-phenyl-2-[(pyrazinylcarbonyl)amino]propanoyl]amino]butyl]boronic acid, N-((1R)-1-(dihydroxyboranyl)-3-methylbutyl)-N(alpha)-(pyrazin-2-ylcarbonyl)-L-phenylalaninamide, N-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-N(alpha)-(pyrazin-2-ylcarbonyl)-L-phenylalaninamide, Bortezomib- Bio-X, Bortezomib [USAN], Velcade (Millenium), 3mg0, BORTEZOMIB [MI], Bortezomib for Injection, BORTEZOMIB [INN], BORTEZOMIB [JAN], BORTEZOMIB [HSDB], PS-341 [Bortezomib], BORTEZOMIB [VANDF], BORTEZOMIB [WHO-DD], MLS004774142, Bortezomib (JAN/USAN/INN), BORTEZOMIB [EMA EPAR], SCHEMBL192129, GTPL6391, BORTEZOMIB [ORANGE BOOK], BORTEZOMIB HYDRATE [JAN], L01XX32, EX-A8373, Tox21_112630, Tox21_112672, BDBM50069989, HB4036, NSC756655, AKOS015909706, Tox21_112672_1, AM81235, CCG-268449, CS-1039, DB00188, NSC-756655, NCGC00242506-01, NCGC00242506-06, NCGC00242506-07, AS-15721, BB164258, HY-10227, NCI60_029010, SMR003500787, Bortezomib (Velcade,MG-341,PS-341)?, B5741, NS00006197, SW208077-3, A18332, D03150, EN300-657180, AB01273951-01, AB01273951-02, AB01273951_03, Q419319, SR-01000939863, SR-01000939863-2, BRD-K88510285-001-02-0, Z2213886907, ((R)-3-methyl-1-((S)-3-phenyl-2-(pyrazine-2-carboxamido)propanamido)butyl)boronicacid, (R)-3-methyl-1-((S)-3-phenyl-2-(pyrazine-6-carboxamido)propanamido)butylboronic acid, [(1R)-3-methyl-1-[(2S)-3-phenyl-2-[(pyrazin-2-yl)formamido]propanamido]butyl]boronic acid, (1R)-3-Methyl-1-({(2S)-3-phenyl-2-[(2-pyrazinylcarbonyl)amino]propanoyl}amino)butylboronic acid, AldrichCPR, (R)-3-METHYL-1-((S)-3-PHENYL-2-(PYRAZINE-2-CARBOXAMIDO)PROPANAMIDO)BUTAN-2-YLBORONIC ACID, [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]-butyl]boronic acid, 1610526-91-4, Boronic acid, (3-methyl-1-((1-oxo-3-phenyl-2-((pyrazinylcarbonyl)amino)propyl)amino)butyl)-, (S-(R,S))-, Boronic acid, [(1(R)-3-methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]-, Radiciol , NSC 681239 , MG 341 , DPBA , Brotezamide , LDP 341
Drug Type	Small molecule
Formula	C₁₉H₂₅BN₄O₄
SMILES	B(C(CC(C)C)NC(=O)C(CC1=CC=CC=C1)NC(=O)C2=NC=CN=C2)(O)O
InChI	1S/C19H25BN4O4/c1-13(2)10-17(20(27)28)24-18(25)15(11-14-6-4-3-5-7-14)23-19(26)16-12-21-8-9-22-16/h3-9,12-13,15,17,27-28H,10-11H2,1-2H3,(H,23,26)(H,24,25)/t15-,17-/m0/s1
InChIKey	GXJABQQUPOEUTA-RDJZCZTQSA-N
CAS Number	179324-69-7
ChEMBL ID	CHEMBL325041
ChEBI ID	CHEBI:52717
TTD ID	D0SH3I
Drug Bank ID	DB00188
KEGG ID	D03150
Toxicity	Organism	Test Type	Route(Dose)
	rat	LD50	intraperitoneal(165 mg/kg)
	mouse	LD50	intraperitoneal(254 mg/kg)
	rat	LD50	oral(322 mg/kg)
Structure			Download 2D MOL 3D MOL

Pair Name	Ursodiol, Bortezomib
Partner Name	Ursodiol
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Biological Phenomena	Induction-->Endoplasmic reticulum stress
Gene Regulation	Up-regulation	Expression	ATF4	hsa468
	Up-regulation	Expression	DDIT3	hsa1649
	Up-regulation	Expression	EIF2AK3	hsa9451
	Up-regulation	Expression	ROS1	hsa6098
In Vitro Model	A-172	Glioblastoma	Homo sapiens (Human)	CVCL_0131
	LN-229	Glioblastoma	Homo sapiens (Human)	CVCL_0393
	U-87MG ATCC	Glioblastoma	Homo sapiens (Human)	CVCL_0022
	U-251MG	Astrocytoma	Homo sapiens (Human)	CVCL_0021
Result	Ursodeoxycholic Acid Inhibits Glioblastoma Progression via Endoplasmic Reticulum Stress Related Apoptosis and Synergizes with the Proteasome Inhibitor Bortezomib

Pair Name	Thymoquinone, Bortezomib
Partner Name	Thymoquinone
Disease Info	[ICD-11: 2A85.5]	Mantle cell lymphoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Expression	CASP3	hsa836
	Down-regulation	Expression	CDH13	hsa1012
	Up-regulation	Expression	COL11A2	hsa1302
	Down-regulation	Expression	IL6	hsa3569
	Down-regulation	Expression	MKI67	hsa4288
	Down-regulation	Expression	RELA	hsa5970
	Down-regulation	Expression	TNF	hsa7124
	Down-regulation	Expression	VEGFA	hsa7422
In Vitro Model	U266B1	Plasma cell myeloma	Homo sapiens (Human)	CVCL_0566
	NCI-H929	Plasma cell myeloma	Homo sapiens (Human)	CVCL_1600
	KMS-11	Plasma cell myeloma	Homo sapiens (Human)	CVCL_2989
	RPMI-8226	Plasma cell myeloma	Homo sapiens (Human)	CVCL_0014
In Vivo Model	Five-week-old athymic nu/nu male Balb/c mice were implanted subcutaneously in the right flank with U266 cells (2×10⁶ cells/100 uL of PBS/Matrigel).
Result	Thymoquinone overcomes chemoresistance and enhances the anticancer effects of bortezomib through abrogation of NF-KappaB regulated gene products in multiple myeloma xenograft mouse model

Pair Name	Solamargine, Bortezomib
Partner Name	Solamargine
Disease Info	[ICD-11: 2A83]	Multiple myeloma		Investigative
Biological Phenomena	Induction-->Autophagy
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Expression	BECN1	hsa8678
	Up-regulation	Cleavage	CASP3	hsa836
	Down-regulation	Expression	MAP1LC3A	hsa84557
	Up-regulation	Expression	MAP1LC3B	hsa81631
In Vitro Model	ARP-1	Plasma cell myeloma	Homo sapiens (Human)	CVCL_D523
In Vitro Model	NCI-H929	Plasma cell myeloma	Homo sapiens (Human)	CVCL_1600
Result	These findings indicate that SM exerts an anti-MM effect, at least in part, by activating cell autophagy and reveal that SM alone or in combination with BTZ is a potential therapeutic strategy for treating MM.

Pair Name	Sanguinarium, Bortezomib
Partner Name	Sanguinarium
Disease Info	[ICD-11: 2A83]	Multiple myeloma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BCL-xL	hsa598
	Down-regulation	Activity	CASP3	hsa836
	Down-regulation	Activity	CASP9	hsa842
	Down-regulation	Expression	CCND1	hsa595
	Down-regulation	Expression	JAK2	hsa3717
	Down-regulation	Cleavage	PARP1	hsa142
	Up-regulation	Expression	PTPN6	hsa5777
	Down-regulation	Expression	STAT3	hsa6774
	Down-regulation	Expression	XIAP	hsa331
In Vitro Model	U266B1	Plasma cell myeloma	Homo sapiens (Human)	CVCL_0566
In Vitro Model	MM1.S	Plasma cell myeloma	Homo sapiens (Human)	CVCL_8792
Result	Our findings demonstrate that SNG induces mitochondrial and caspase-dependent apoptosis, generates oxidative stress, and suppresses MM cell lines proliferation. In addition, co-treatment of MM cell lines with sub-toxic doses of SNG and BTZ potentiated the cytotoxic activity. These results would suggest that SNG could be developed into therapeutic agent either alone or in combination with other anticancer drugs in MM.

Pair Name	Piperlongumine, Bortezomib
Partner Name	Piperlongumine
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Induction-->Endoplasmic reticulum stress
Gene Regulation	Up-regulation	Expression	ATF4	hsa468
	Up-regulation	Expression	ATF6	hsa22926
	Up-regulation	Expression	DDIT3	hsa1649
	Up-regulation	Cleavage	PARP1	hsa142
	Up-regulation	Expression	XBP1	hsa7494
In Vitro Model	KKU-M055	Intrahepatic cholangiocarcinoma	Homo sapiens (Human)	CVCL_M258
In Vitro Model	KKU-213A	Intrahepatic cholangiocarcinoma	Homo sapiens (Human)	CVCL_M261
Result	Piperlongumine and bortezomib synergically inhibit cholangiocarcinoma via ER stress-induced cell death

Pair Name	Lycorine, Bortezomib
Partner Name	Lycorine
Disease Info	[ICD-11: 2A83]	Multiple myeloma		Investigative
Biological Phenomena	Inhibition-->Autophagy
Gene Regulation	Down-regulation	Phosphorylation	BCL2	hsa596
	Down-regulation	Expression	BECN1	hsa8678
	Down-regulation	Expression	HMGB1	hsa3146
	Down-regulation	Expression	MAP1LC3B	hsa81631
	Down-regulation	Phosphorylation	MAP2K7	hsa5609
	Down-regulation	Phosphorylation	MAPK1	hsa5594
In Vitro Model	ARH-77	Plasma cell myeloma	Homo sapiens (Human)	CVCL_1072
	MM1.S	Plasma cell myeloma	Homo sapiens (Human)	CVCL_8792
	NCI-H929	Plasma cell myeloma	Homo sapiens (Human)	CVCL_1600
In Vivo Model	The mice were subcutaneously inoculated in the flank with 5×10⁶ MM.1S cells in 100 µl of phosphate-buffered saline.
Result	We observed higher HMGB1 expression in bortezomib resistant cells and the combination of bortezomib plus lycorine was highly efficient in vitro and in vivo myeloma models as well as in re-sensitizing resistant cells to bortezomib. These observations indicate lycorine as an effective autophagy inhibitor and reveal that lycorine alone or in combination with bortezomib is a potential therapeutic strategy.

Pair Name	Luteolin, Bortezomib
Partner Name	Luteolin
Disease Info	[ICD-11: 2A83]	Multiple myeloma		Investigative
Gene Regulation	Down-regulation	Expression	ALDH1A1	hsa216
	Down-regulation	Phosphorylation	SMAD2	hsa4087
	Down-regulation	Expression	TGFBR1	hsa7046
In Vitro Model	ANBL-6	Plasma cell myeloma	Homo sapiens (Human)	CVCL_5425
	ARP-1	Plasma cell myeloma	Homo sapiens (Human)	CVCL_D523
	KMS-11	Plasma cell myeloma	Homo sapiens (Human)	CVCL_2989
	MM1.S	Plasma cell myeloma	Homo sapiens (Human)	CVCL_8792
	RPMI-8226	Plasma cell myeloma	Homo sapiens (Human)	CVCL_0014
In Vivo Model	Female BALB/c nude mice were subcutaneously inoculated in the flank with 5×10⁶ luciferase-labeled ARP1 cells in 200 μL of PBS. NOD/ShiLtJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt (NCG) mice were subcutaneously inoculated in the flank with 1×107 luciferase-labeled ARP1-BR cells in 200 μL of PBS.
Result	Our findings suggested that LUT is a promising agent that manifests MMSCs to overcome BTZ resistance, alone or in combination with BTZ, and thus, is a potential therapeutic drug for the treatment of MM.

Pair Name	Flavokawain B, Bortezomib
Partner Name	Flavokawain B
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	CDKN1A	hsa1026
	Up-regulation	cleavage	PARP1	hsa142
	Up-regulation	Expression	PSMD9	hsa5715
	Down-regulation	Expression	SKP2	hsa6502
In Vitro Model	LNCaP	Prostate carcinoma	Homo sapiens (Human)	CVCL_0395
	PC-3	Prostate carcinoma	Homo sapiens (Human)	CVCL_0035
	LNCaP C4-2B	Prostate carcinoma	Homo sapiens (Human)	CVCL_4784
Result	These findings provide a rationale for further investigating combination of FKB and Bortezomib for treatment of RB deficient, castration-resistant prostate cancer.

Pair Name	Delta-Tocotrienol, Bortezomib
Partner Name	Delta-Tocotrienol
Disease Info	[ICD-11: 2A00-2F9Z]	Solid tumour or cancer		Investigative
Gene Regulation	Down-regulation	Expression	NFE2L1	hsa4779
	Down-regulation	Expression	POMP	KEGG ID N.A.
	Down-regulation	Expression	PSMA7	KEGG ID N.A.
	Down-regulation	Expression	PSMB7	KEGG ID N.A.
	Down-regulation	Expression	PSMC4	KEGG ID N.A.
In Vitro Model	NCI-H2452	Pleural biphasic mesothelioma	Homo sapiens (Human)	CVCL_1553
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0480
	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
Result	These findings suggested that the inactivation of NFE2L1 by T3, TOS, and T3E is essential to potentiate the cytotoxic effect of the proteasome inhibitor, BTZ, in solid cancers.

Pair Name	Caffeic acid phenethyl ester, Bortezomib
Partner Name	Caffeic acid phenethyl ester
Disease Info	[ICD-11: 2A83]	Multiple myeloma		Investigative
Gene Regulation	Down-regulation	Expression	IL6	hsa3569
Gene Regulation	Down-regulation	Activity	NFKB1	hsa4790
In Vitro Model	ARH-77	Plasma cell myeloma	Homo sapiens (Human)	CVCL_1072
In Vivo Model	Female BALB/c mice (5–6 weeks old) were use in this study.
Result	We think that our study, which is the first to demonstrate the in vitro and in vivo effectiveness of the.combined use of CAPE and bortezomib, will be a pioneer for future human applications of CAPE in MM.

Pair Name	Beta-Elemene, Bortezomib
Partner Name	Beta-Elemene
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G2/M phase
Gene Regulation	Up-regulation	Cleavage	CASP3	hsa836
	Down-regulation	Expression	CCNB1	hsa891
	Up-regulation	Expression	CDKN1A	hsa1026
	Down-regulation	Expression	NFKBIA	hsa4792
	Down-regulation	Expression	RELA	hsa5970
	Down-regulation	Expression	TP53	hsa7157
In Vitro Model	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0480
In Vitro Model	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0186
In Vivo Model	Bortezomib or elemene alone inhibited the tumor growth to a certain extent, while the combination treatment significantly enhanced the antitumor activity relative to bortezomib alone assessed by tumor growth curve and endpoint tumor weight, suggesting that elemene boosts bortezomib’s anti-pancreatic cancer activity, and their combination displays significant antitumor efficacy with no obvious systematic toxicity.
Result	Elemene sensitizes pancreatic cancer cells to bortezomib by enhancing proteasome inhibition via molecular patch mechanism

Pair Name	Anacardic Acid, Bortezomib
Partner Name	Anacardic Acid
Disease Info	[ICD-11: 2A83]	Multiple myeloma		Investigative
Biological Phenomena	Induction-->Endoplasmic reticulum stress
Gene Regulation	Up-regulation	Expression	ATF4	hsa468
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP8	hsa841
	Up-regulation	Cleavage	CASP9	hsa842
	Up-regulation	Expression	DDIT3	hsa1649
	Up-regulation	Phosphorylation	EIF2S1	hsa1965
	Up-regulation	Expression	HSPA4	hsa3308
	Up-regulation	Expression	HSPA5	hsa3309
	Up-regulation	Cleavage	PARP1	hsa142
In Vitro Model	U266B1	Plasma cell myeloma	Homo sapiens (Human)	CVCL_0566
Result	The results of the present study suggest that AA/Bor combination may be a potential therapeutic strategy for MM treatment.

Pair Name	Epigallocatechin gallate, Bortezomib
Partner Name	Epigallocatechin gallate
Disease Info	[ICD-11: 2A00-2F9Z]	Solid tumour or cancer	Investigative
In Vivo Model	Four- to 6-week-old male athymic nu/nu mice were obtained from Harlan (Indianapolis, IN) and implanted subcutaneously with 5 × 106 RPMI/8226 multiple myeloma cells.
Result	(-)-epigallocatechin gallate (EGCG) and other polyphenols with 1,2-benzenediol moieties, effectively prevented tumor cell death induced by BZM in vitro and in vivo. This pronounced antagonistic function of EGCG was evident only with boronic acid-based proteasome inhibitors (BZM, MG-262, PS-IX), but not with several non-boronic acid proteasome inhibitors (MG-132, PS-I, nelfinavir). EGCG directly reacted with BZM and blocked its proteasome inhibitory function; as a consequence, BZM could not trigger endoplasmic reticulum stress or caspase-7 activation, and did not induce tumor cell death. Taken together, our results indicate that green tea polyphenols may have the potential to negate the therapeutic efficacy of BZM and suggest that consumption of green tea products may be contraindicated during cancer therapy with BZM.