Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0326)

Name	Talaroconvolutin A
Synonyms	Talaroconvolutin A; TalaA; (-)-talaroconvolutin A; CHEMBL495874; CHEBI:173105; (5Z)-3-[(1R,2S,4aS,6S,8aR)-3,4a,6-trimethyl-2-[(E)-4-methylhex-2-en-2-yl]-2,5,6,7,8,8a-hexahydro-1H-naphthalene-1-carbonyl]-5-[(4-hydroxyphenyl)methylidene]pyrrol-2-one; (5Z)-5-(4-hydroxybenzylidene)-3-({(1R,2S,4aS,6S,8aR)-3,4a,6-trimethyl-2-[(2E)-4-methylhex-2-en-2-yl]-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl}carbonyl)-1,5-dihydro-2H-pyrrol-2-one; 273199-42-1 Click to Show/Hide
Structure
Structure	3D MOL 2D MOL
Formula	C32H41NO3
IUPAC Name	(5Z)-3-[(1R,2S,4aS,6S,8aR)-3,4a,6-trimethyl-2-[(E)-4-methylhex-2-en-2-yl]-2,5,6,7,8,8a-hexahydro-1H-naphthalene-1-carbonyl]-5-[(4-hydroxyphenyl)methylidene]pyrrol-2-one
Canonical SMILES	CCC(C)C=C(C)C1C(C2CCC(CC2(C=C1C)C)C)C(=O)C3=CC(=CC4=CC=C(C=C4)O)NC3=O
InChI	InChI=1S/C32H41NO3/c1-7-19(2)14-21(4)28-22(5)18-32(6)17-20(3)8-13-27(32)29(28)30(35)26-16-24(33-31(26)36)15-23-9-11-25(34)12-10-23/h9-12,14-16,18-20,27-29,34H,7-8,13,17H2,1-6H3,(H,33,36)/b21-14+,24-15-/t19?,20-,27+,28-,29+,32+/m0/s1
InChIKey	QCTUYJGFLVZOTL-NKPJVERHSA-N
PubChem CID	6475761

Full List of Ferroptosis Target Related to This Drug

Hydroperoxide isomerase ALOXE3 (ALOXE3)

Target Info

In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target				[1]
Target for Ferroptosis	Driver
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In Vivo Model	5 x 10⁶ HCT116 cells were inoculated subcutaneously in the underarm of Balb/c nude female mice (5-week old). The inoculated mice were randomly divided into two groups (6 mice each group). When the tumor reached 300 mm³, the drug group was given TalaA intraperitoneally at a dose of 6.0 mg/kg, and the control group was given the same dose of cosolvent-corn oil. The drug (or cosolvent) was injected every 2 days. Body weight and tumor volume were measured every 2 days. Click to Show/Hide
Response regulation	Talaroconvolutin A (TalaA) downregulated the expression of the channel protein solute carrier family 7 member 11 (SLC7A11) but upregulated arachidonate lipoxygenase 3 (ALOXE3), promoting ferroptosis. TalaA causes upregulation of HMOX1 which lead to the degradation of heme and the release of free iron, accumulating in mitochondria and giving rise to lipid peroxidation. TalaA could be a new potential powerful drug candidate for colorectal cancer therapy.

Heme oxygenase 1 (HMOX1)

Target Info

In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target				[1]
Target for Ferroptosis	Driver/Suppressor
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In Vivo Model	5 x 10⁶ HCT116 cells were inoculated subcutaneously in the underarm of Balb/c nude female mice (5-week old). The inoculated mice were randomly divided into two groups (6 mice each group). When the tumor reached 300 mm³, the drug group was given TalaA intraperitoneally at a dose of 6.0 mg/kg, and the control group was given the same dose of cosolvent-corn oil. The drug (or cosolvent) was injected every 2 days. Body weight and tumor volume were measured every 2 days. Click to Show/Hide
Response regulation	Talaroconvolutin A (TalaA) downregulated the expression of the channel protein solute carrier family 7 member 11 (SLC7A11) but upregulated arachidonate lipoxygenase 3 (ALOXE3), promoting ferroptosis. TalaA causes upregulation of HMOX1 which lead to the degradation of heme and the release of free iron, accumulating in mitochondria and giving rise to lipid peroxidation. TalaA could be a new potential powerful drug candidate for colorectal cancer therapy.

Cystine/glutamate transporter (SLC7A11)

Target Info

In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target				[1]
Target for Ferroptosis	Suppressor
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In Vivo Model	5 x 10⁶ HCT116 cells were inoculated subcutaneously in the underarm of Balb/c nude female mice (5-week old). The inoculated mice were randomly divided into two groups (6 mice each group). When the tumor reached 300 mm³, the drug group was given TalaA intraperitoneally at a dose of 6.0 mg/kg, and the control group was given the same dose of cosolvent-corn oil. The drug (or cosolvent) was injected every 2 days. Body weight and tumor volume were measured every 2 days. Click to Show/Hide
Response regulation	Talaroconvolutin A (TalaA) downregulated the expression of the channel protein solute carrier family 7 member 11 (SLC7A11) but upregulated arachidonate lipoxygenase 3 (ALOXE3), promoting ferroptosis. TalaA causes upregulation of HMOX1 which lead to the degradation of heme and the release of free iron, accumulating in mitochondria and giving rise to lipid peroxidation. TalaA could be a new potential powerful drug candidate for colorectal cancer therapy.

References

Ref 1	Discovery of a novel ferroptosis inducer-talaroconvolutin A-killing colorectal cancer cells in vitro and in vivo. Cell Death Dis. 2020 Nov 17;11(11):988. doi: 10.1038/s41419-020-03194-2.