InterPAD - DETAILS

Dipotassium Salt, Gossypol, Gossypol, Gossypol Dipotassium Salt, Gossypol Sodium Salt, Gossypol, (+)-Isomer, Gossypol, (+-)-Isomer, Gossypol, (-)-Isomer, Sodium Salt, Gossypol

No.	Title	Href
1	The ponatinib/gossypol novel combination provides enhanced anticancer activity against murine solid Ehrlich carcinoma via triggering apoptosis and inhibiting proliferation/angiogenesis. Toxicol Appl Pharmacol. 2021 Dec 1;432:115767. doi: 10.1016/j.taap.2021.115767.	`Click`
2	Gossypol and an HMT G9a inhibitor act in synergy to induce cell death in pancreatic cancer cells. Cell Death Dis. 2013 Jun 27;4(6):e690. doi: 10.1038/cddis.2013.191.	`Click`
3	Gossypol sensitizes the antitumor activity of 5-FU through down-regulation of thymidylate synthase in human colon carcinoma cells. Cancer Chemother Pharmacol. 2015 Sep;76(3):575-86. doi: 10.1007/s00280-015-2749-0.	`Click`
4	AT-101 enhances gefitinib sensitivity in non-small cell lung cancer with EGFR T790M mutations. BMC Cancer. 2016 Jul 18;16:491. doi: 10.1186/s12885-016-2519-3.	`Click`
5	Downregulation of BCL2 by AT-101 enhances the antileukaemic effect of lenalidomide both by an immune dependant and independent manner. Br J Haematol. 2012 Apr;157(1):59-66. doi: 10.1111/j.1365-2141.2011.08984.x.	`Click`
6	Synthetic lethality of combined AT-101 with idarubicin in acute myeloid leukemia via blockade of DNA repair and activation of intrinsic apoptotic pathway. Cancer Lett. 2019 Oct 1;461:31-43. doi: 10.1016/j.canlet.2019.07.003.	`Click`
7	Trastuzumab in combination with AT-101 induces cytotoxicity and apoptosis in Her2 positive breast cancer cells. Future Oncol. 2020 Jan;16(3):4485-4495. doi: 10.2217/fon-2019-0521.	`Click`
8	Gossypol, a phytochemical with BH3-mimetic property, sensitizes cultured thoracic cancer cells to Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand. J Thorac Cardiovasc Surg. 2006 Dec;132(6):1356-62. doi: 10.1016/j.jtcvs.2006.07.025.	`Click`
9	(-)Gossypol and its combination with imatinib induce apoptosis in human chronic myeloid leukemic cells. Leuk Lymphoma. 2007 Nov;48(11):2204-12. doi: 10.1080/10428190701583991.	`Click`
10	Targeting apoptosis in the hormone- and drug-resistant prostate cancer cell line, DU-145, by gossypol/zoledronic acid combination. Cell Biol Int. 2009 Nov;33(11):1165-72. doi: 10.1016/j.cellbi.2009.08.006.	`Click`
11	Combination of L-gossypol and low-concentration doxorubicin induces apoptosis in human synovial sarcoma cells. Mol Med Rep. 2015 Oct;12(4):5924-32. doi: 10.3892/mmr.2015.4127.	`Click`
12	Combination therapy with gossypol reveals synergism against gemcitabine resistance in cancer cells with high BCL-2 expression. PLoS One. 2012;7(12):e50786. doi: 10.1371/journal.pone.0050786.	`Click`

No.

Title

Href

The ponatinib/gossypol novel combination provides enhanced anticancer activity against murine solid Ehrlich carcinoma via triggering apoptosis and inhibiting proliferation/angiogenesis. Toxicol Appl Pharmacol. 2021 Dec 1;432:115767. doi: 10.1016/j.taap.2021.115767.

Click

Gossypol and an HMT G9a inhibitor act in synergy to induce cell death in pancreatic cancer cells. Cell Death Dis. 2013 Jun 27;4(6):e690. doi: 10.1038/cddis.2013.191.

Click

Gossypol sensitizes the antitumor activity of 5-FU through down-regulation of thymidylate synthase in human colon carcinoma cells. Cancer Chemother Pharmacol. 2015 Sep;76(3):575-86. doi: 10.1007/s00280-015-2749-0.

Click

AT-101 enhances gefitinib sensitivity in non-small cell lung cancer with EGFR T790M mutations. BMC Cancer. 2016 Jul 18;16:491. doi: 10.1186/s12885-016-2519-3.

Click

Downregulation of BCL2 by AT-101 enhances the antileukaemic effect of lenalidomide both by an immune dependant and independent manner. Br J Haematol. 2012 Apr;157(1):59-66. doi: 10.1111/j.1365-2141.2011.08984.x.

Click

Synthetic lethality of combined AT-101 with idarubicin in acute myeloid leukemia via blockade of DNA repair and activation of intrinsic apoptotic pathway. Cancer Lett. 2019 Oct 1;461:31-43. doi: 10.1016/j.canlet.2019.07.003.

Click

Trastuzumab in combination with AT-101 induces cytotoxicity and apoptosis in Her2 positive breast cancer cells. Future Oncol. 2020 Jan;16(3):4485-4495. doi: 10.2217/fon-2019-0521.

Click

Gossypol, a phytochemical with BH3-mimetic property, sensitizes cultured thoracic cancer cells to Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand. J Thorac Cardiovasc Surg. 2006 Dec;132(6):1356-62. doi: 10.1016/j.jtcvs.2006.07.025.

Click

(-)Gossypol and its combination with imatinib induce apoptosis in human chronic myeloid leukemic cells. Leuk Lymphoma. 2007 Nov;48(11):2204-12. doi: 10.1080/10428190701583991.

Click

Targeting apoptosis in the hormone- and drug-resistant prostate cancer cell line, DU-145, by gossypol/zoledronic acid combination. Cell Biol Int. 2009 Nov;33(11):1165-72. doi: 10.1016/j.cellbi.2009.08.006.

Click

Combination of L-gossypol and low-concentration doxorubicin induces apoptosis in human synovial sarcoma cells. Mol Med Rep. 2015 Oct;12(4):5924-32. doi: 10.3892/mmr.2015.4127.

Click

Combination therapy with gossypol reveals synergism against gemcitabine resistance in cancer cells with high BCL-2 expression. PLoS One. 2012;7(12):e50786. doi: 10.1371/journal.pone.0050786.

Click

Name	Gossypol
PubChem CID	3503
Molecular Weight	518.6g/mol
Synonyms	Dipotassium Salt, Gossypol, Gossypol, Gossypol Dipotassium Salt, Gossypol Sodium Salt, Gossypol, (+)-Isomer, Gossypol, (+-)-Isomer, Gossypol, (-)-Isomer, Sodium Salt, Gossypol
Formula	C₃₀H₃₀O₈
SMILES	CC1=CC2=C(C(=C(C(=C2C(C)C)O)O)C=O)C(=C1C3=C(C4=C(C=C3C)C(=C(C(=C4C=O)O)O)C(C)C)O)O
InChI	1S/C30H30O8/c1-11(2)19-15-7-13(5)21(27(35)23(15)17(9-31)25(33)29(19)37)22-14(6)8-16-20(12(3)4)30(38)26(34)18(10-32)24(16)28(22)36/h7-12,33-38H,1-6H3
InChIKey	QBKSWRVVCFFDOT-UHFFFAOYSA-N
CAS Number	20300-26-9
ChEMBL ID	CHEMBL51483
Herb ID	HBIN028351
Drug Bank ID	DB13044
KEGG ID	C07667
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	MuZei
Use Part	Aerial Parts
Habitat	HeiLongJiang, JiLin, LiaoNing, HeBei, Shaanxi, GanSu, XinJiang, SiChuan
Flavor	Sweet, Bitter
Meridian Tropism	Lung, Liver
Species	>Kingdom: Viridiplantae 　-->Phylum: Streptophyta 　　-->Class: Equisetopsida 　　　-->Order: Equisetales 　　　　-->Family: Equisetaceae 　　　　　-->Genus: Equisetum 　　　　　　-->Species: Equisetum hyemale

Chineses Pinyin	DiTangHua
Use Part	Flower, Branchlet-Leaf
Habitat	JiangSu, ZheJiang, JiangXi, HuNan, HuBei, SiChuan, GuangDong, YunNan, HeNan
Flavor	Bitter, Astringent
Meridian Tropism	Lung, Stomach, Spleen
Species	>Kingdom: Viridiplantae 　-->Phylum: Streptophyta 　　-->Class: Equisetopsida 　　　-->Order: Rosales 　　　　-->Family: Rosaceae 　　　　　-->Genus: Kerria 　　　　　　-->Species: Kerria japonica

Chineses Pinyin	LuDiMian
Use Part	Tomentum Of Seed
Habitat	China
Flavor	Sweet
Meridian Tropism	Heart, Liver
Species	>Kingdom: Viridiplantae 　-->Phylum: Streptophyta 　　-->Class: Equisetopsida 　　　-->Order: Malvales 　　　　-->Family: Malvaceae 　　　　　-->Genus: Gossypium 　　　　　　-->Species: Gossypium hirsutum

Chineses Pinyin	WenJing
Use Part	Whole Herb
Habitat	HeiLongJiang, JiLin, LiaoNing, BeiJing, TianJin, HeBei, ShanXi, NeiMengGu, Shaanxi, XinJiang, ShanDong, JiangSu, AnHui, JiangXi, HuBei, HuNan, SiChuan, GuiZhou, XiZang
Flavor	Bitter
Meridian Tropism	Lung, Stomach, Liver
Species	>Kingdom: Viridiplantae 　-->Phylum: Streptophyta 　　-->Class: Equisetopsida 　　　-->Order: Equisetales 　　　　-->Family: Equisetaceae 　　　　　-->Genus: Equisetum 　　　　　　-->Species: Equisetum arvense

Chineses Pinyin	SanYang
Use Part	Whole herb
Species	>Kingdom: Viridiplantae 　-->Phylum: Streptophyta 　　-->Class: Equisetopsida 　　　-->Order: Malvales 　　　　-->Family: Malvaceae 　　　　　-->Genus: Thespesia 　　　　　　-->Species: Thespesia populnea

Pair Name	Gossypol, Ponatinib
Partner Name	Ponatinib
Disease Info	[ICD-11: 2A00-2F9Z]	Solid tumour or cancer		Investigative
Biological Phenomena	Inhibition-->Angiogenesis
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Expression	CASP9	hsa842
	Down-regulation	Expression	FGFR4	hsa2264
	Up-regulation	Expression	TP53	hsa7157
	Down-regulation	Expression	VEGFA	hsa7422
In Vivo Model	EAC cells were maintained through serial intraperitoneal inoculation of saline solution containing 106 cells/mouse into female Swiss albino mice (El-Wahab and Fouda, 2009). After 10 days, the host mice were euthanized by cervical dislocation, and the cells were recovered by collecting them using a syringe, washing them in normal saline, and counting them.
Result	Gossypol could be used as an adjuvant medication for ponatinib in cancer treatment, possibly leading to successful dose reductions and fewer side effects; however, further research is needed before a clinical application could be feasible.

Pair Name	Gossypol, BRD4770
Partner Name	BRD4770
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Biological Phenomena	Induction-->Autophagy
Gene Regulation	Up-regulation	Expression	BNIP3	hsa664
	Up-regulation	Expression	MAP1LC3B	hsa81631
	Up-regulation	Phosphorylation	TP53	hsa7157
In Vitro Model	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0480
Result	The combination of gossypol and BRD4770 increased LC3-II levels and the autophagosome number in PANC-1 cells, and the compound combination appears to act in a BNIP3 (B-cell lymphoma 2 19-kDa interacting protein)-dependent manner, suggesting that these compounds act together to induce autophagy-related cell death in pancreatic cancer cells.

Pair Name	Gossypol, Fluorouracil
Partner Name	Fluorouracil
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Gene Regulation	Up-regulation	Cleavage	CASP3	hsa836
	Down-regulation	Expression	CCND1	hsa595
	Down-regulation	Phosphorylation	MTOR	hsa2475
	Up-regulation	Cleavage	PARP1	hsa142
	Down-regulation	Phosphorylation	RPS6KB1	hsa6198
	Down-regulation	Expression	TYMS	hsa7298
In Vitro Model	HT-29	Colon adenocarcinoma	Homo sapiens (Human)	CVCL_0320
	HCT 116	Colon carcinoma	Homo sapiens (Human)	CVCL_0291
	RKO	Colon carcinoma	Homo sapiens (Human)	CVCL_0504
Result	These findings suggest that gossypol-mediated down-regulation of TS, cyclin D1, and the mTOR/p70S6K1 signaling pathways enhances the anti-tumor effect of 5-FU. Ultimately, our data exposed a new action for gossypol as an enhancer of 5-FU-induced cell growth suppression.

Pair Name	Gossypol, Gefitinib
Partner Name	Gefitinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BCL-xL	hsa598
	Up-regulation	Cleavage	CASP3	hsa836
	Down-regulation	Phosphorylation	EGFR	hsa1956
	Down-regulation	Phosphorylation	MAPK1	hsa5594
In Vitro Model	PC-9-GR-high	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_S706
In Vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_1511
Result	AT-101 enhances gefitinib sensitivity in non-small cell lung cancer with EGFR T790M mutations.

Pair Name	Gossypol, lenalidomide
Partner Name	lenalidomide
Disease Info	[ICD-11: 2A82]	Chronic lymphocytic leukemia		Investigative
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Phosphorylation	MAPK3	hsa5595
	Down-regulation	Expression	MCL1	hsa4170
In Vitro Model	CII	Chronic lymphocytic leukemia	Homo sapiens (Human)	CVCL_0D73
Result	Downregulation of BCL2 by AT-101 enhances the antileukaemic effect of lenalidomide both by an immune dependant and independent manner.

Pair Name	Gossypol, Idarubicin
Partner Name	Idarubicin
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia		Investigative
Biological Phenomena	Induction-->DNA damage
Gene Regulation	Down-regulation	Phosphorylation	ATM	hsa472
	Down-regulation	Phosphorylation	ATR	hsa545
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BCL-xL	hsa598
	Up-regulation	Cleavage	CASP3	hsa836
	Down-regulation	Phosphorylation	CHEK1	hsa1111
	Down-regulation	Phosphorylation	CHEK2	hsa11200
	Down-regulation	Expression	MCL1	hsa4170
	Up-regulation	Cleavage	PARP1	hsa142
	Down-regulation	Expression	XIAP	hsa331
In Vivo Model	16 male NOD-Prkdc−/−IL2rg−/- mice (NPI, IDMO ltd., Beijing, China) were intravenously injected with 2×10⁶ splenic cells of humanized xenograft mice generated from an AML patient carrying FLT3-ITD mutation via tail vein after irradiation (1 Gy).
Result	These findings suggest that combinatorial therapy with AT-101 and IDA selectively eliminates leukemia stem-like cells both in vitro and in vivo, representing a potent and alternative salvage therapy for the treatment of relapsed and refractory patients with AML.

Pair Name	Gossypol, Trastuzumab
Partner Name	Trastuzumab
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	AKT1	hsa207
Gene Regulation	Down-regulation	Expression	PIK3CA	hsa5290
In Vitro Model	SK-BR-3	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0033
In Vitro Model	MDA-MB-453	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0418
Result	The trastuzumab/AT-101 combination may be a good candidate for patients with trastuzumab-resistant Her2-positive breast cancer and inhibition of the PI3K/AKT pathway may be one of the underlying mechanisms.

Pair Name	Gossypol, TRAIL/Apo2L
Partner Name	TRAIL/Apo2L
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Mitochondria-dependent apoptosis
Gene Regulation	Up-regulation	Activity	CASP3	hsa836
In Vitro Model	NCI-H460	Lung large cell carcinoma	Homo sapiens (Human)	CVCL_0459
In Vitro Model	NCI-H322	Minimally invasive lung adenocarcinoma	Homo sapiens (Human)	CVCL_1556
Result	Gossypol profoundly sensitizes thoracic cancer cells to the cytotoxic effect of Apo2L/TRAIL via activation of the mitochondria-dependent death signaling pathway. This study provides evidence for the profound anticancer activity of this drug combination and should be further evaluated as a novel targeted molecular therapeutic for thoracic cancers.

Pair Name	Gossypol, Imatinib
Partner Name	Imatinib
Disease Info	[ICD-11: 2B33.4]	Leukemia		Investigative
Biological Phenomena	Induction-->Mitochondria-mediated apoptosis
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BCL-xL	hsa598
	Up-regulation	Cleavage	CASP3	hsa836
	Down-regulation	Expression	MCL1	hsa4170
In Vitro Model	K-562	Blast phase chronic myelogenous leukemia	Homo sapiens (Human)	CVCL_0004
Result	These results suggest that (-)gossypol induced apoptosis in K562 cells through a mitochondria pathway and that the combination of imatinib and (-)gossypol might be an effective treatment for CML.

Pair Name	Gossypol, Zoledronic acid
Partner Name	Zoledronic acid
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	BAD	hsa572
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BIRC2	hsa329
	Down-regulation	Expression	BIRC3	hsa330
	Down-regulation	Expression	BIRC5	hsa332
	Down-regulation	Expression	BIRC7	hsa79444
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Expression	CDKN1B	hsa1027
	Down-regulation	Expression	CLSPN	hsa63967
	Up-regulation	Expression	FAS	hsa355
	Down-regulation	Expression	HMOX1	hsa3162
	Down-regulation	Expression	HSPD1	hsa3329
	Down-regulation	Expression	PON2	hsa5445
	Down-regulation	Expression	TP53	hsa7157
In Vitro Model	DU145	Prostate carcinoma	Homo sapiens (Human)	CVCL_0105
Result	GP significantly enhances the anti-tumor activity of ZA in hormone- and drug-resistant prostate cancer cells by targeting many pivotal apoptosis-related proteins.

Pair Name	Gossypol, Doxorubicin
Partner Name	Doxorubicin
Disease Info	[ICD-11: 2B5A]	Biphasic synovial sarcoma		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in S phase
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP9	hsa842
In Vitro Model	SW982	Biphasic synovial sarcoma	Homo sapiens (Human)	CVCL_1734
Result	Combination therapy with L gossypol and low-concentration doxorubicin inhibited cell proliferation and induced apoptosis in SW982 HSSCs at a significantly greater level compared with either treatment alone

Pair Name	Gossypol, Gemcitabine
Partner Name	Gemcitabine
Disease Info	[ICD-11: 2A00-2F9Z]	Solid tumour or cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BCL-xL	hsa598
	Up-regulation	Expression	MCL1	hsa4170
	Up-regulation	Expression	PMAIP1	hsa5366
In Vitro Model	CNE-1	Nasopharyngeal carcinoma	Homo sapiens (Human)	CVCL_6888
	YCC-16	Gastric adenocarcinoma	Homo sapiens (Human)	CVCL_9649
	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
Result	Combination therapy with gossypol reveals synergism against gemcitabine resistance in cancer cells with high BCL-2 expression