InterPAD - DETAILS

metformin, 657-24-9, 1,1-Dimethylbiguanide, N,N-dimethylimidodicarbonimidic diamide, Fluamine, Metiguanide, Dimethylbiguanide, Flumamine, Gliguanid, Haurymelin, Metformine, Melbin, Imidodicarbonimidic diamide, N,N-dimethyl-, N,N-Dimethylbiguanide, Islotin, Dimethyldiguanide, N1,N1-Dimethylbiguanide, DMGG, NNDG, N,N-Dimethyldiguanide, Diabetosan, Metformina, Metforminum, Glifage, Siofor, Metformine [INN-French], Metforminum [INN-Latin], LA-6023, BIGUANIDE, 1,1-DIMETHYL-, 3-(diaminomethylidene)-1,1-dimethylguanidine, Dimethylbiguanid, 1,1-Dimethyl biguanide, Metformin extended release, EINECS 211-517-8, CCRIS 9321, CHEBI:6801, DTXSID2023270, UNII-9100L32L2N, 9100L32L2N, CHEMBL1431, DTXCID803270, Imidodicarbonimidic diamide-, N,N-dimethyl-, Metformina [DCIT], Metformina [Spanish], Metformine (INN-French), Metforminum (INN-Latin), Dimethylguanylguanidine, Metformin [USAN:INN:BAN], C4H11N5, MLS000028493, [14C]metformin, [14C]-metformin, Metformin (USAN/INN), NCGC00016564-01, SMR000058277, CAS-1115-70-4, N,N-dimethylguanylguanidine, Dianben, Obimet, N-dimethylbiguanide, MF8, Metforminum (Latin), DMBG, Glucophage (Salt/Mix), METFORMIN [INN], n',n'-dimethylbiguanide, METFORMIN [MI], METFORMIN [USAN], Prestwick0_000004, Prestwick1_000004, Prestwick2_000004, Prestwick3_000004, METFORMIN [VANDF], N,N-Dimethylguanylguanidin, METFORMIN [WHO-DD], SCHEMBL8944, BSPBio_000007, BSPBio_002314, KBioGR_002310, KBioSS_002312, cid_14219, LA 6023 (Salt/Mix), BIDD:GT0697, SPBio_001928, N(1),N(1)-dimethylbiguanide, BPBio1_000009, GTPL4503, GTPL4779, SCHEMBL9913821, SCHEMBL10276396, BDBM57047, KBio2_002310, KBio2_004878, KBio2_007446, KBio3_002790, A10BA02, cMAP_000016, HMS2089D19, HY-B0627, Tox21_302370, BBL012337, BDBM50229665, HSCI1_000295, MFCD00242652, NSC813213, s5958, STK011633, STL483693, STL484070, N,N-Dimethyltriimidodicarbonic diamide, AKOS000121065, AKOS005206848, AKOS015966566, CCG-102605, DB00331, NSC-813213, 3-carbamimidoyl-1,1-dimethyl-guanidine, NCGC00016564-02, NCGC00016564-03, NCGC00016564-05, NCGC00016564-07, NCGC00188959-01, NCGC00255255-01, AC-32484, AS-65365, CAS-657-24-9, SBI-0206876.P001, 1-carbamimidamido-N,N-dimethylmethanimidamide, CS-0009563, FT-0628266, NS00000333, EN300-23696, A19551, C07151, D04966, D72476, EN300-746417, Q19484, (E)-3-[Amino(dimethylamino)methylidene]guanidine, 1-[(E)-amino(dimethylamino)methylidene]guanidine, W-109589, {[amino(dimethylamino)methylidene]amino}methanimidamide, BRD-K79602928-003-04-1, BRD-K79602928-003-08-2, 3-(diaminomethylene)-1,1-dimethyl-guanidine;hydrochloride, [(E)-[AMINO(DIMETHYLAMINO)METHYLIDENE]AMINO]METHANIMIDAMIDE, 3-[bis(azanyl)methylidene]-1,1-dimethyl-guanidine;hydrochloride

No.	Title	Href
1	DDInter: an online drug-drug interaction database towards improving clinical decision-making and patient safety. Nucleic Acids Res. 2022;50(D1):D1200-D1207. doi:10.1093/nar/gkab880	`Click`
2	Tangeretin boosts the anticancer activity of metformin in breast cancer cells via curbing the energy production. Phytomedicine. 2021 Mar;83:153470. doi: 10.1016/j.phymed.2021.153470.	`Click`
3	Co-Treatment with Sulforaphane and Nano-Metformin Molecules Accelerates Apoptosis in HER2+ Breast Cancer Cells by Inhibiting Key Molecules. Nutr Cancer. 2020;72(5):835-848. doi: 10.1080/01635581.2019.1655073.	`Click`
4	Synergistic Anti-proliferative Effects of Metformin and Silibinin Combination on T47D Breast Cancer Cells via hTERT and Cyclin D1 Inhibition. Drug Res (Stuttg). 2018 Dec;68(12):710-716. doi: 10.1055/a-0631-8046.	`Click`
5	Anti-proliferative and anti-apoptotic potential effects of epigallocatechin-3-gallate and/or metformin on hepatocellular carcinoma cells: in vitro study. Mol Biol Rep. 2019 Apr;46(2):2039-2047. doi: 10.1007/s11033-019-04653-6.	`Click`
6	Crocin and Metformin suppress metastatic breast cancer progression via VEGF and MMP9 downregulations: in vitro and in vivo studies. Mol Cell Biochem. 2021 Sep;476(9):3341-3351. doi: 10.1007/s11010-020-04043-8.	`Click`
7	Synergistic Growth Inhibitory Effects of Chrysin and Metformin Combination on Breast Cancer Cells through hTERT and Cyclin D1 Suppression. Asian Pac J Cancer Prev. 2018 Apr 25;19(4):977-982. doi: 10.22034/APJCP.2018.19.4.977.	`Click`
8	Lower dose of metformin combined with artesunate induced autophagy-dependent apoptosis of glioblastoma by activating ROS-AMPK-mTOR axis. Exp Cell Res. 2023 Sep 1;430(1):113691. doi: 10.1016/j.yexcr.2023.113691.	`Click`
9	Combination of aloin and metformin enhances the antitumor effect by inhibiting the growth and invasion and inducing apoptosis and autophagy in hepatocellular carcinoma through PI3K/AKT/mTOR pathway. Cancer Med. 2020 Feb;9(3):1141-1151. doi: 10.1002/cam4.2723.	`Click`
10	Honokiol inhibits the growth of hormone-resistant breast cancer cells: its promising effect in combination with metformin. Res Pharm Sci. 2023 Aug 20;18(5):580-591. doi: 10.4103/1735-5362.383712.	`Click`

No.

Title

Href

DDInter: an online drug-drug interaction database towards improving clinical decision-making and patient safety. Nucleic Acids Res. 2022;50(D1):D1200-D1207. doi:10.1093/nar/gkab880

Click

Tangeretin boosts the anticancer activity of metformin in breast cancer cells via curbing the energy production. Phytomedicine. 2021 Mar;83:153470. doi: 10.1016/j.phymed.2021.153470.

Click

Co-Treatment with Sulforaphane and Nano-Metformin Molecules Accelerates Apoptosis in HER2+ Breast Cancer Cells by Inhibiting Key Molecules. Nutr Cancer. 2020;72(5):835-848. doi: 10.1080/01635581.2019.1655073.

Click

Synergistic Anti-proliferative Effects of Metformin and Silibinin Combination on T47D Breast Cancer Cells via hTERT and Cyclin D1 Inhibition. Drug Res (Stuttg). 2018 Dec;68(12):710-716. doi: 10.1055/a-0631-8046.

Click

Anti-proliferative and anti-apoptotic potential effects of epigallocatechin-3-gallate and/or metformin on hepatocellular carcinoma cells: in vitro study. Mol Biol Rep. 2019 Apr;46(2):2039-2047. doi: 10.1007/s11033-019-04653-6.

Click

Crocin and Metformin suppress metastatic breast cancer progression via VEGF and MMP9 downregulations: in vitro and in vivo studies. Mol Cell Biochem. 2021 Sep;476(9):3341-3351. doi: 10.1007/s11010-020-04043-8.

Click

Synergistic Growth Inhibitory Effects of Chrysin and Metformin Combination on Breast Cancer Cells through hTERT and Cyclin D1 Suppression. Asian Pac J Cancer Prev. 2018 Apr 25;19(4):977-982. doi: 10.22034/APJCP.2018.19.4.977.

Click

Lower dose of metformin combined with artesunate induced autophagy-dependent apoptosis of glioblastoma by activating ROS-AMPK-mTOR axis. Exp Cell Res. 2023 Sep 1;430(1):113691. doi: 10.1016/j.yexcr.2023.113691.

Click

Combination of aloin and metformin enhances the antitumor effect by inhibiting the growth and invasion and inducing apoptosis and autophagy in hepatocellular carcinoma through PI3K/AKT/mTOR pathway. Cancer Med. 2020 Feb;9(3):1141-1151. doi: 10.1002/cam4.2723.

Click

Honokiol inhibits the growth of hormone-resistant breast cancer cells: its promising effect in combination with metformin. Res Pharm Sci. 2023 Aug 20;18(5):580-591. doi: 10.4103/1735-5362.383712.

Click

Name	Metformin
PubChem CID	4091
Molecular Weight	129.16g/mol
Synonyms	metformin, 657-24-9, 1,1-Dimethylbiguanide, N,N-dimethylimidodicarbonimidic diamide, Fluamine, Metiguanide, Dimethylbiguanide, Flumamine, Gliguanid, Haurymelin, Metformine, Melbin, Imidodicarbonimidic diamide, N,N-dimethyl-, N,N-Dimethylbiguanide, Islotin, Dimethyldiguanide, N1,N1-Dimethylbiguanide, DMGG, NNDG, N,N-Dimethyldiguanide, Diabetosan, Metformina, Metforminum, Glifage, Siofor, Metformine [INN-French], Metforminum [INN-Latin], LA-6023, BIGUANIDE, 1,1-DIMETHYL-, 3-(diaminomethylidene)-1,1-dimethylguanidine, Dimethylbiguanid, 1,1-Dimethyl biguanide, Metformin extended release, EINECS 211-517-8, CCRIS 9321, CHEBI:6801, DTXSID2023270, UNII-9100L32L2N, 9100L32L2N, CHEMBL1431, DTXCID803270, Imidodicarbonimidic diamide-, N,N-dimethyl-, Metformina [DCIT], Metformina [Spanish], Metformine (INN-French), Metforminum (INN-Latin), Dimethylguanylguanidine, Metformin [USAN:INN:BAN], C4H11N5, MLS000028493, [14C]metformin, [14C]-metformin, Metformin (USAN/INN), NCGC00016564-01, SMR000058277, CAS-1115-70-4, N,N-dimethylguanylguanidine, Dianben, Obimet, N-dimethylbiguanide, MF8, Metforminum (Latin), DMBG, Glucophage (Salt/Mix), METFORMIN [INN], n',n'-dimethylbiguanide, METFORMIN [MI], METFORMIN [USAN], Prestwick0_000004, Prestwick1_000004, Prestwick2_000004, Prestwick3_000004, METFORMIN [VANDF], N,N-Dimethylguanylguanidin, METFORMIN [WHO-DD], SCHEMBL8944, BSPBio_000007, BSPBio_002314, KBioGR_002310, KBioSS_002312, cid_14219, LA 6023 (Salt/Mix), BIDD:GT0697, SPBio_001928, N(1),N(1)-dimethylbiguanide, BPBio1_000009, GTPL4503, GTPL4779, SCHEMBL9913821, SCHEMBL10276396, BDBM57047, KBio2_002310, KBio2_004878, KBio2_007446, KBio3_002790, A10BA02, cMAP_000016, HMS2089D19, HY-B0627, Tox21_302370, BBL012337, BDBM50229665, HSCI1_000295, MFCD00242652, NSC813213, s5958, STK011633, STL483693, STL484070, N,N-Dimethyltriimidodicarbonic diamide, AKOS000121065, AKOS005206848, AKOS015966566, CCG-102605, DB00331, NSC-813213, 3-carbamimidoyl-1,1-dimethyl-guanidine, NCGC00016564-02, NCGC00016564-03, NCGC00016564-05, NCGC00016564-07, NCGC00188959-01, NCGC00255255-01, AC-32484, AS-65365, CAS-657-24-9, SBI-0206876.P001, 1-carbamimidamido-N,N-dimethylmethanimidamide, CS-0009563, FT-0628266, NS00000333, EN300-23696, A19551, C07151, D04966, D72476, EN300-746417, Q19484, (E)-3-[Amino(dimethylamino)methylidene]guanidine, 1-[(E)-amino(dimethylamino)methylidene]guanidine, W-109589, {[amino(dimethylamino)methylidene]amino}methanimidamide, BRD-K79602928-003-04-1, BRD-K79602928-003-08-2, 3-(diaminomethylene)-1,1-dimethyl-guanidine;hydrochloride, [(E)-[AMINO(DIMETHYLAMINO)METHYLIDENE]AMINO]METHANIMIDAMIDE, 3-[bis(azanyl)methylidene]-1,1-dimethyl-guanidine;hydrochloride
Drug Type	Small molecule
Formula	C₄H₁₁N₅
SMILES	CN(C)C(=N)N=C(N)N
InChI	1S/C4H11N5/c1-9(2)4(7)8-3(5)6/h1-2H3,(H5,5,6,7,8)
InChIKey	XZWYZXLIPXDOLR-UHFFFAOYSA-N
CAS Number	657-24-9
ChEMBL ID	CHEMBL1431
ChEBI ID	CHEBI:6801
TTD ID	D0D7LA
Drug Bank ID	DB00331
KEGG ID	C07151
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

Pair Name	Tangeretin, Metformin
Partner Name	Tangeretin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->ROS accumulation
Gene Regulation	Down-regulation	Phosphorylation	ABCB1	hsa5243
	Down-regulation	Phosphorylation	ABCC1	hsa4363
	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP7	hsa840
	Down-regulation	Expression	CDK2	hsa1017
	Down-regulation	Expression	CDK4	hsa1019
	Down-regulation	Phosphorylation	MAPK1	hsa5594
	Up-regulation	Cleavage	PARP1	hsa142
	Up-regulation	Phosphorylation	PRKAA1	hsa5562
	Up-regulation	Activity	ROS1	hsa6098
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
In Vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
Result	The current work underscores the importance of metformin as an ERMA in tackling breast cancer and as a novel approach to boost its anticancer activity via a synergistic combination with tangeretin.

Pair Name	Sulforaphane, Metformin
Partner Name	Sulforaphane
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	CD44	hsa960
	Down-regulation	Expression	CTNNB1	hsa1499
	Down-regulation	Expression	ERBB2	hsa2064
	Down-regulation	Expression	SRC	hsa6714
	Down-regulation	Expression	WNT1	hsa7471
In Vitro Model	BT-474	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0179
Result	Our data indicate that SLFN and MTFN can reduce cancer cell viability via both collaborative and differential effects and suggest that MTFN increases SLFN effectiveness by targeting common molecules/pathways downstream of HER2 and key for CSC signaling.

Pair Name	Silibinin, Metformin
Partner Name	Silibinin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Proliferation
Gene Regulation	Down-regulation	Expression	CCND1	hsa595
Gene Regulation	Down-regulation	Expression	TERT	hsa7015
In Vitro Model	T-47D	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0553
Result	The results provide evidence that synergistic antiproliferative effects of MET and SIL, linking to the down-regulation of Cyclin D1 and hTERT genes, and propose that MET+SIL may have therapeutic value in breast cancer therapy.

Pair Name	Epigallocatechin gallate, Metformin
Partner Name	Epigallocatechin gallate
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G0/G1 phase
Gene Regulation	Up-regulation	Expression	CASP3	hsa836
	Down-regulation	Expression	CCND1	hsa595
	Down-regulation	Expression	GPC3	hsa2719
	Down-regulation	Expression	VEGFA	hsa7422
In Vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens (Human)	CVCL_0027
Result	Anti-proliferative and anti-apoptotic potential effects of epigallocatechin-3-gallate and/or metformin on hepatocellular carcinoma cells: in vitro study

Pair Name	Crocin, Metformin
Partner Name	Crocin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Inhibition-->Cell metastasis
Gene Regulation	Down-regulation	Expression	MMP9	hsa4318
Gene Regulation	Down-regulation	Expression	VEGFA	hsa7422
In Vitro Model	4T1	Malignant neoplasms of the mouse mammary gland	Mus musculus (Mouse)	CVCL_0125
In Vivo Model	1×10⁶ 4T1 cells suspended in 0.2 ml phosphate-buffered saline and inoculated into the left dorsal flank regions of the mice.
Result	These findings suggest that a combination of crocin and metformin could serve as a novel therapeutic approach to enhance the effectiveness of metastatic breast cancer therapy.

Pair Name	Chrysin, Metformin
Partner Name	Chrysin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Gene Regulation	Down-regulation	Expression	CCND1	hsa595
Gene Regulation	Down-regulation	Expression	TERT	hsa7015
In Vitro Model	T-47D	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0553
Result	The conmbination of metformin and chrysin suppressing hTERT and cyclin D1 gene expression might offer an appropriate approach for breast cancer therapy.

Pair Name	Artesunate, Metformin
Partner Name	Artesunate
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Biological Phenomena	Induction-->Autophagy
Gene Regulation	Up-regulation	Expression	CASP9	hsa842
	Down-regulation	Expression	MAP1LC3A	hsa84557
	Up-regulation	Expression	MAP1LC3B	hsa81631
	Down-regulation	Phosphorylation	MTOR	hsa2475
	Up-regulation	Phosphorylation	PRKAA1	hsa5562
	Down-regulation	Expression	SQSTM1	hsa8878
In Vitro Model	U-118MG	Astrocytoma	Homo sapiens (Human)	CVCL_0633
In Vitro Model	U-251MG	Astrocytoma	Homo sapiens (Human)	CVCL_0021
Result	The study findings suggest that MET used in combination with ART can induce autophagy-dependent apoptosis in GBM cells by activating the ROS-AMPK-mTOR pathway, providing a potential new treatment for GBM.

Pair Name	Aloin, Metformin
Partner Name	Aloin
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Induction-->Autophagy
Gene Regulation	Up-regulation	Activity	AKT1	hsa207
	Up-regulation	Activity	MTOR	hsa2475
	Up-regulation	Activity	PIK3CA	hsa5290
In Vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens (Human)	CVCL_0027
In Vitro Model	BEL-7402	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_5492
In Vivo Model	For xenograft study, mice were inoculated subcutaneously into the right-back with 7.5×10⁶ HepG2 cells in 200 μl PBS and Matrigel (1:1).
Result	Our research demonstrated that the concomitant treatment with aloin and MET enhances the antitumor effect by inhibiting the growth and invasion as well as inducing apoptosis and autophagy in HCC through PI3K/AKT/mTOR pathway.

Pair Name	Honokiol, Metformin
Partner Name	Honokiol
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Cleavage	PARP1	hsa142
	Down-regulation	Phosphorylation	RPS6KB1	hsa6198
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
	SK-BR-3	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0033
Result	The combination of honokiol with metformin is considered an effective approach to induce death in hormone-resistant cells. Honokiol is of interest as a natural compound with antiproliferative activity against breast cancers, including resistant tumors.

Pair Name	Niacinamide, Metformin
Partner Name	Niacinamide
Result	The efficacy of insulin and other antidiabetic agents may be diminished by certain drugs, including atypical antipsychotics, corticosteroids, diuretics, estrogens, gonadotropin-releasing hormone agonists, human growth hormone, phenothiazines, progestins, protease inhibitors, sympathomimetic amines, thyroid hormones, L-asparaginase, alpelisib, copanlisib, danazol, diazoxide, isoniazid, megestrol, omacetaxine, phenytoin, tagraxofusp, temsirolimus, as well as pharmacologic dosages of nicotinic acid and adrenocorticotropic agents. These drugs may interfere with blood glucose control because they can cause hyperglycemia, glucose intolerance, new-onset diabetes mellitus, and/or exacerbation of preexisting diabetes.