InterPAD - DETAILS

5,6-epoxy-4,22,27-trihydroxy-1-oxoergosta-2,24-dienoic acid delta-lactone, withaferin A

No.	Title	Href
1	Synergistic antitumor activity of withaferin A combined with oxaliplatin triggers reactive oxygen species-mediated inactivation of the PI3K/AKT pathway in human pancreatic cancer cells. Cancer Lett. 2015 Feb 1;357(1):219-230. doi: 10.1016/j.canlet.2014.11.026.	`Click`
2	Synergistic antitumor effect of 5-fluorouracil and withaferin-A induces endoplasmic reticulum stress-mediated autophagy and apoptosis in colorectal cancer cells. Am J Cancer Res. 2020 Mar 1;10(3):799-815.	`Click`
3	A novel combination of withaferin A and sorafenib shows synergistic efficacy against both papillary and anaplastic thyroid cancers. Am J Surg. 2012 Dec;204(6):895-900; discussion 900-1. doi: 10.1016/j.amjsurg.2012.07.027.	`Click`
4	Withaferin A Increases the Effectiveness of Immune Checkpoint Blocker for the Treatment of Non-Small Cell Lung Cancer. Cancers (Basel). 2023 Jun 7;15(12):3089. doi: 10.3390/cancers15123089.	`Click`

No.

Title

Href

Synergistic antitumor activity of withaferin A combined with oxaliplatin triggers reactive oxygen species-mediated inactivation of the PI3K/AKT pathway in human pancreatic cancer cells. Cancer Lett. 2015 Feb 1;357(1):219-230. doi: 10.1016/j.canlet.2014.11.026.

Click

Synergistic antitumor effect of 5-fluorouracil and withaferin-A induces endoplasmic reticulum stress-mediated autophagy and apoptosis in colorectal cancer cells. Am J Cancer Res. 2020 Mar 1;10(3):799-815.

Click

A novel combination of withaferin A and sorafenib shows synergistic efficacy against both papillary and anaplastic thyroid cancers. Am J Surg. 2012 Dec;204(6):895-900; discussion 900-1. doi: 10.1016/j.amjsurg.2012.07.027.

Click

Withaferin A Increases the Effectiveness of Immune Checkpoint Blocker for the Treatment of Non-Small Cell Lung Cancer. Cancers (Basel). 2023 Jun 7;15(12):3089. doi: 10.3390/cancers15123089.

Click

Name	Withaferin A
PubChem CID	265237
Molecular Weight	470.6g/mol
Synonyms	5,6-epoxy-4,22,27-trihydroxy-1-oxoergosta-2,24-dienoic acid delta-lactone, withaferin A
Formula	C₂₈H₃₈O₆
SMILES	CC1=C(C(=O)OC(C1)C(C)C2CCC3C2(CCC4C3CC5C6(C4(C(=O)C=CC6O)C)O5)C)CO
InChI	1S/C28H38O6/c1-14-11-21(33-25(32)17(14)13-29)15(2)18-5-6-19-16-12-24-28(34-24)23(31)8-7-22(30)27(28,4)20(16)9-10-26(18,19)3/h7-8,15-16,18-21,23-24,29,31H,5-6,9-13H2,1-4H3/t15-,16-,18+,19-,20-,21+,23-,24+,26+,27-,28+/m0/s1
InChIKey	DBRXOUCRJQVYJQ-CKNDUULBSA-N
CAS Number	5119-48-2
ChEMBL ID	CHEMBL517080
ChEBI ID	CHEBI:69120
KEGG ID	C08841
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

Chineses Pinyin	ShanDouGen
Use Part	Root, Rhizome
Habitat	GuangXi
Flavor	Bitter
Meridian Tropism	Lung, Stomach
Species	>Kingdom: Viridiplantae 　-->Phylum: Streptophyta 　　-->Class: Equisetopsida 　　　-->Order: Fabales 　　　　-->Family: Fabaceae 　　　　　-->Genus: Sophora 　　　　　　-->Species: Sophora tonkinensis

Chineses Pinyin	YangJinHua
Use Part	Flower
Habitat	China
Flavor	Pungent
Meridian Tropism	Lung, Liver
Species	>Kingdom: Viridiplantae 　-->Phylum: Streptophyta 　　-->Class: Equisetopsida 　　　-->Order: Solanales 　　　　-->Family: Solanaceae 　　　　　-->Genus: Datura 　　　　　　-->Species: Datura metel

Chineses Pinyin	ShuiQie
Use Part	Root
Habitat	TaiWan, GuangDong, GuangXi, YunNan
Flavor	Bland
Species	>Kingdom: Viridiplantae 　-->Phylum: Streptophyta 　　-->Class: Equisetopsida 　　　-->Order: Solanales 　　　　-->Family: Solanaceae 　　　　　-->Genus: Solanum 　　　　　　-->Species: Solanum torvum

Pair Name	Withaferin A, Fluorouracil
Partner Name	Fluorouracil
Disease Info	[ICD-11: 2B91.Z]	Colorectal cancer		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G2/M phase
Gene Regulation	Up-regulation	Expression	HSPA5	hsa3309
	Up-regulation	Expression	EIF2AK3	hsa9451
	Up-regulation	Expression	DDIT3	hsa1649
	Up-regulation	Expression	ATF4	hsa468
	Up-regulation	Expression	EIF2S1	hsa1965
	Down-regulation	Expression	CTNNB1	hsa1499
In Vitro Model	SW480	Colon adenocarcinoma	Homo sapiens (Human)	CVCL_0546
	HT-29	Colon adenocarcinoma	Homo sapiens (Human)	CVCL_0320
	HCT 116	Colon carcinoma	Homo sapiens (Human)	CVCL_0291
Result	Synergistic antitumor effect of 5-fluorouracil and withaferin-A induces endoplasmic reticulum stress-mediated autophagy and apoptosis in colorectal cancer cells

Pair Name	Withaferin A, Sorafenib
Partner Name	Sorafenib
Disease Info	[ICD-11: 2D10.Z]	Thyroid cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Phosphorylation	CASP3	hsa836
Gene Regulation	Down-regulation	Expression	PARP1	hsa142
In Vitro Model	B-CPAP	Poorly differentiated thyroid gland carcinoma	Homo sapiens (Human)	CVCL_0153
In Vitro Model	SW1736	Thyroid gland anaplastic carcinoma	Homo sapiens (Human)	CVCL_3883
Result	Combination therapy with sorafenib + withaferin showed synergistic efficacy in papillary and anaplastic cancers in vitro with significant induction of apoptosis. This combination achieved potent anticancer activity with lower overall doses of sorafenib, indicating a potential strategy to decrease sorafenib toxicity in future translational studies.

Pair Name	Withaferin A, Immune checkpoint blockers
Partner Name	Immune checkpoint blockers
Disease Info	[ICD-11: 2C25.Z]	Lung cancer		Investigative
Biological Phenomena	Induction-->Immunomodulatory
Gene Regulation	Up-regulation	Expression	CD274	hsa29126
In Vivo Model	To establish the LLC syngeneic tumors, C57BL/6 mice were injected with a half million cells on the right flank and monitored until tumors were first palpable (2–3 mm diameter).
Result	Our results demonstrate that WFA sensitizes NSCLC to α-PD-L1 in part via activation of ROS.

Pair Name	Withaferin A, Oxaliplatin
Partner Name	Oxaliplatin
Disease Info	[ICD-11: 2C10.Z]	Pancreatic cancer		Investigative
Biological Phenomena	Induction-->ROS accumulation
Gene Regulation	Down-regulation	Phosphorylation	PIK3R1	hsa5295
	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Phosphorylation	MAPK14	hsa1432
	Up-regulation	Phosphorylation	MAPK8	hsa5599
	Down-regulation	Phosphorylation	PDPK1	hsa5170
	Down-regulation	Phosphorylation	BRAF	hsa673
	Down-regulation	Expression	XIAP	hsa331
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Activity	CASP3	hsa836
In Vitro Model	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0480
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0428
	SW1990	Pancreatic adenocarcinoma	Homo sapiens (Human)	CVCL_1723
Result	These results support the notion that combination treatment with oxaliplatin and WA could facilitate development of an effective strategy for PC treatment.