InterPAD - DETAILS

chuanxiongzine, ligustrazine, Liqustrazine, tetramethyl pyrazine, tetramethylpyrazine, tetramethylpyrazine hydrochloride, TMPZ

No.	Title	Href
1	Combination treatment of ligustrazine piperazine derivate DLJ14 and adriamycin inhibits progression of resistant breast cancer through inhibition of the EGFR/PI3K/Akt survival pathway and induction of apoptosis. Drug Discov Ther. 2014 Feb;8(1):33-41. doi: 10.5582/ddt.8.33.	`Click`
2	Ligustrazine-Derived Chalcones-Modified Platinum(IV) Complexes Intervene in Cisplatin Resistance in Pancreatic Cancer through Ferroptosis and Apoptosis. J Med Chem. 2023 Oct 12;66(19):13587-13606. doi: 10.1021/acs.jmedchem.3c00922.	`Click`

No.

Title

Href

Combination treatment of ligustrazine piperazine derivate DLJ14 and adriamycin inhibits progression of resistant breast cancer through inhibition of the EGFR/PI3K/Akt survival pathway and induction of apoptosis. Drug Discov Ther. 2014 Feb;8(1):33-41. doi: 10.5582/ddt.8.33.

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Ligustrazine-Derived Chalcones-Modified Platinum(IV) Complexes Intervene in Cisplatin Resistance in Pancreatic Cancer through Ferroptosis and Apoptosis. J Med Chem. 2023 Oct 12;66(19):13587-13606. doi: 10.1021/acs.jmedchem.3c00922.

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Name	2,3,5,6-Tetramethylpyrazine
PubChem CID	14296
Molecular Weight	136.19g/mol
Synonyms	chuanxiongzine, ligustrazine, Liqustrazine, tetramethyl pyrazine, tetramethylpyrazine, tetramethylpyrazine hydrochloride, TMPZ
Formula	C₈H₁₂N₂
SMILES	CC1=C(N=C(C(=N1)C)C)C
InChI	1S/C8H12N2/c1-5-6(2)10-8(4)7(3)9-5/h1-4H3
InChIKey	FINHMKGKINIASC-UHFFFAOYSA-N
CAS Number	1124-11-4
ChEMBL ID	CHEMBL303697
ChEBI ID	CHEBI:133246
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	ChuanXiong
Use Part	Rhizome
Flavor	Pungent
Meridian Tropism	Liver; Gallbladder; Pericardium
Species	>Kingdom: Viridiplantae 　-->Phylum: Streptophyta 　　-->Class: Magnoliopsida 　　　-->Order: Apiales 　　　　-->Family: Apiaceae 　　　　　-->Genus: Ligusticum 　　　　　　-->Species: Ligusticum chuanxiong

Pair Name	2,3,5,6-Tetramethylpyrazine, Doxorubicin
Partner Name	Doxorubicin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Mitochondria-mediated apoptosis
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP9	hsa842
	Down-regulation	Expression	CCNA2	hsa890
	Up-regulation	Expression	CDKN1A	hsa1026
	Down-regulation	Phosphorylation	EGFR	hsa1956
	Down-regulation	Expression	PIK3CA	hsa5290
	Up-regulation	Expression	TP53	hsa7157
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
In Vitro Model	K562/A02	Blast phase chronic myelogenous leukemia	Homo sapiens (Human)	CVCL_0368
Result	DLJ14 and Adr combination treatment may inhibit proliferation of Adr-resistant human breast cancer cells through inhibition of the EGFR/PI3K/Akt survival pathway and induction of apoptosis via the mitochondrial-mediated apoptosis pathway.

Pair Name	2,3,5,6-Tetramethylpyrazine, Cisplatin
Partner Name	Cisplatin
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Biological Phenomena	Induction-->Ferroptosis
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP9	hsa842
	Up-regulation	Expression	CYCS	hsa54205
	Down-regulation	Expression	GPX4	hsa2879
	Down-regulation	Expression	NFE2L2	hsa4780
	Up-regulation	Cleavage	PARP1	hsa142
	Down-regulation	Expression	SLC7A11	hsa23657
In Vitro Model	PANC-1/CDDP	Cisplatin-resistant pancreatic ductal adenocarcinoma	Homo sapiens (Human)	N.A.
In Vivo Model	The mice were inoculated subcutaneously with PANC-1/CDDP cells (1×10⁷/mouse) into the right flanks to establish PANC-1/CDDP xenograft models.
Result	A series of ligustrazine-derived chalcones-modified platinum(IV) complexes were synthesized and evaluated for their anti-proliferative potency and generated an optimal platinum(IV) complex 16a. The above-described results indicated that 16a obtained different anti-cancer mechanisms of CDDP, which could initiate mitochondria-dependent apoptosis and xCT-GPX4 axial-mediated ferroptosis in PANC-1/CDDP cells.