Pair Name	Nobiletin, Bicalutamide
Partner Name	Bicalutamide
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	MAPK1	hsa5594
	Down-regulation	Expression	NFKB1	hsa4790
	Down-regulation	Expression	STAT3	hsa6774
In Vitro Model	VCaP	Prostate carcinoma	Homo sapiens (Human)	CVCL_2235
	PC-3	Prostate carcinoma	Homo sapiens (Human)	CVCL_0035
Result	NBT and BCT combination reduced key cellular signaling regulators including: p-Erk/Erk, p-STAT3/STAT3 and NF-κB. Overall, these results suggest that NBT combination with BCT may be an effective treatment for prostate cancer.

Pair Name	Nobiletin, Palbociclib
Partner Name	Palbociclib
Disease Info	[ICD-11: 2C90.0]	Renal cell carcinoma		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G0/G1 phase
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Phosphorylation	CDK2	hsa1017
	Down-regulation	Expression	CDKN1A	hsa1026
	Down-regulation	Expression	PSMD9	hsa5715
	Down-regulation	Phosphorylation	RB1	hsa5925
	Down-regulation	Expression	SKP2	hsa6502
In Vivo Model	A total of 2×10⁶ 786-O cells were mixed 1:1 with Matrigel (BD Biosciences) in a total volume of 200 μL, and were injected subcutaneously into the right flank side of nude mice.
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
Partner Name	Sorafenib
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G0/G1 phase
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Up-regulation	Expression	CDKN1A	hsa1026
	Up-regulation	Expression	RB1	hsa5925
In Vitro Model	PC-3	Prostate carcinoma	Homo sapiens (Human)	CVCL_0035
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	Nobiletin, Vorinostat
Partner Name	Vorinostat
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Apoptosis and autophagy
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BCL-xL	hsa598
	Down-regulation	Expression	BECN1	hsa8678
	Up-regulation	Expression	BID	hsa637
	Up-regulation	Expression	BIM	hsa10018
	Up-regulation	Cleavage	CASP9	hsa842
	Up-regulation	Expression	MAP1LC3B	hsa81631
	Down-regulation	Expression	MCL1	hsa4170
	Down-regulation	Phosphorylation	MTOR	hsa2475
	Up-regulation	Cleavage	PARP1	hsa142
	Down-regulation	Phosphorylation	PIK3CA	hsa5290
In Vitro Model	PC-3	Prostate carcinoma	Homo sapiens (Human)	CVCL_0035
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0480
	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
	NCI-H69	Lung small cell carcinoma	Homo sapiens (Human)	CVCL_1579
	NCI-H82	Lung small cell carcinoma	Homo sapiens (Human)	CVCL_1591
In Vivo Model	A subcutaneous injection of 5×10⁶ H82 cells was administered into the right flank of each BALB/c nude mouse.
Result	The combination of nobiletin with vorinostat increased histone H3K9 and H3K27 acetylation levels in SCLC mouse tumor tissue and enhanced the expression of the BH3-only proteins BIM and BID. We conclude that nobiletin is a novel natural BH3 mimetic that can cooperate with vorinostat to induce apoptosis and autophagy in SCLC.