InterPAD - DETAILS

methotrexate, 59-05-2, Rheumatrex, Amethopterin, Methylaminopterin, Metatrexan, Hdmtx, Abitrexate, Trexall, Mexate, Ledertrexate, Methylaminopterinum, (S)-2-(4-(((2,4-Diaminopteridin-6-yl)methyl)(methyl)amino)benzamido)pentanedioic acid, Methotrexatum, Antifolan, MTX, 4-Amino-10-methylfolic acid, Amethopterine, Metotrexato, Emtexate, Maxtrex, Rasuvo, Methotrexate hydrate, A-Methopterin, L-Amethopterin, A-Methpterin, Amethopterin L-, Folex-Pfs, Methotrexat-Ebewe, NSC-740, Methotrexate, L-, N-Bismethylpteroylglutamic acid, Farmitrexat, Medsatrexate, Methoblastin, Methotextrate, Methotrexat, Metotressato, Brimexate, Emthexat, Emthexate, Fauldexato, Lantarel, Lumexon, Metrotex, Novatrex, Otrexup, Tremetex, Trexeron, Trixilem, Texate, Metex, Mexate-Aq, alpha-Methopterin, CL-14377, Folex, NCI-C04671, JYLAMVO, Methotrexate Lpf, CCRIS 1109, Nordimet, Xatmep, EMT 25,299, 133073-73-1, 4-Aminomethylpteroylglutamic acid, HSDB 3123, NSC 740, CL 14377, UNII-YL5FZ2Y5U1, Methotrexatum [INN-Latin], Metotrexato [INN-Spanish], EINECS 200-413-8, YL5FZ2Y5U1, R 9985, REDITREX, NSC740, DTXSID4020822, CHEBI:44185, AI3-25299, TCMDC-125858, X 133, 4-Amino-N(sup 10)-methylpteroylglutamic acid, ADX-2191, MPI-2505, WR-19039, CHEMBL34259, DTXCID80822, (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]pentanedioic acid, R-9985, Kyselina 4-amino-N(sup 10)-methylpteroylglutamova, N-(p-(((2,4-Diamino-6-pteridyl)methyl)methylamino)benzoyl)glutamic acid, L-(+)-N-(p-(((2,4-Diamino-6-pteridinyl)methyl)methylamino)benzoyl)glutamic acid, N-(4-(((2,4-Diamino-6-pteridinyl)methyl)methylamino)benzoyl)-L-glutamicacid, N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid, N-(p-(((2,4-Diamino-6-pteridinyl)methyl)methylamino)benzoyl)-L-(+)-glutamic acid, N-[(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}phenyl)carbonyl]-L-glutamic acid, Methotrexate [USAN:USP:INN:BAN:JAN], NCGC00025060-04, 4-amino-N(10)-methylpteroylglutamic acid, MFCD00150847, Kyselina N-(p-((2,4-diamino-6-pteridinylmethyl)methylamino)benzoyl)-L-glutamova, METHOTREXATE (IARC), METHOTREXATE [IARC], Methotrexatum (INN-Latin), Metotrexato (INN-Spanish), (2S)-2-[(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}phenyl)formamido]pentanedioic acid, Glutamic acid, N-(p-(((2,4-diamino-6-pteridinyl)methyl)methylamino)benzoyl)-, L-, METHOTREXATE (MART.), METHOTREXATE [MART.], METHOTREXATE (USP-RS), METHOTREXATE [USP-RS], Metotressato [DCIT], Methotrexate, d-, METHOTREXATE (EP MONOGRAPH), METHOTREXATE (USP IMPURITY), METHOTREXATE [EP MONOGRAPH], METHOTREXATE [USP IMPURITY], METHOTREXATE (USP MONOGRAPH), METHOTREXATE [USP MONOGRAPH], MLS001401431, [3H]methotrexate, Methotrexate (hydrate), Methotrexate (USAN:USP:INN:BAN:JAN), SMR000112001, [3H]-methotrexate, folic acid antagonist, 4-Amino-10-methylfolic acid hydrate, SR-01000075682, SMR000449324, Methotrexate (1.0mg/mL in Methanol with 0.1N NaOH), TCMDC-125488, Metolate, Antifolan hydrate, Intradose-MTX, MTX hydrate, 1dhi, 1dhj, 2drc, 4ocx, (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methyl-amino]benzoyl]amino]pentanedioic acid, CAS-59-05-2, Prestwick_322, Otrexup (TN), Xatmep (TN), L-METHOTREXATE, OTREXUP PFS, Kyselina 4-amino-N(sup 10)-methylpteroylglutamova [Czech], Methylaminopterin; MTX, DL-Amethopterin hydrate, Spectrum_001836, Tocris-1230, 4kn0, Methylaminopterin hydrate, Prestwick0_000135, Prestwick1_000135, Prestwick2_000135, Spectrum2_001077, Spectrum3_000497, Spectrum4_000616, Spectrum5_000958, Abitrexate (Methotrexate), METHOTREXATE [MI], METHOTREXATE [INN], METHOTREXATE [JAN], METHOTREXATE [HSDB], METHOTREXATE [USAN], NCIMech_000767, SCHEMBL3711, Kyselina N-(p-((2,4-diamino-6-pteridinylmethyl)methylamino)benzoyl)-L-glutamova [Czech], METHOTREXATE [VANDF], BIDD:PXR0175, Lopac0_000020, KBioGR_001172, KBioSS_002341, Methotrexate Methylaminopterin, MLS000049968, MLS002154208, DivK1c_000114, METHOTREXATE [WHO-DD], METHOTREXATE [WHO-IP], SPBio_001094, SPBio_002149, Amethopterin (hydrate); CL14377 (hydrate); WR19039 (hydrate), AMY235, cid_126941, cid_165528, GTPL4674, GTPL4815, SCHEMBL12421860, SCHEMBL23111732, BDBM18050, BDBM66082, HMS500F16, KBio1_000114, KBio2_002338, KBio2_004906, KBio2_007474, KBio3_001493, Methotrexate (JP17/USP/INN), L01BA01, L04AX03, g301, NINDS_000114, Bio1_000486, Bio1_000975, Bio1_001464, HMS1568K12, HMS2095K12, HMS2233O18, HMS3260C21, HMS3414L09, HMS3678L07, HMS3712K12, METHOTREXATE [ORANGE BOOK], APC-2002, BCP13701, GLUTAMIC ACID, N-(P-(((2,4-DIAMINO-6-PTERIDINYL)METHYL)METHYLAMINO)BENZOYL)-, L-(+)-, MPI-5004, Tox21_110944, Tox21_300269, Tox21_500020, CCG-35800, EMT-25299, METHOTREXATUM [WHO-IP LATIN], MFCD00064370, s1210, STL535338, (4-(((2,4-diaminopteridin-6-yl)methyl)(methyl)amino)benzoyl)-L-glutamic acid, AKOS016340329, Tox21_110944_1, CL14377, CS-1732, DB00563, KS-5093, LP00020, SDCCGSBI-0050009.P003, IDI1_000114, SMP2_000020, (methyl)amino)benzamido)pentanedioic acid, NCGC00025060-01, NCGC00025060-02, NCGC00025060-03, NCGC00025060-05, NCGC00025060-06, NCGC00025060-07, NCGC00025060-08, NCGC00025060-09, NCGC00025060-10, NCGC00025060-11, NCGC00025060-12, NCGC00025060-13, NCGC00025060-15, NCGC00025060-16, NCGC00254216-01, NCGC00260705-01, HY-14519, EU-0100020, FT-0601523, FT-0630651, G-301, NS00098764, SW198601-3, Methotrexate 1.0 mg/ml in Dimethyl Sulfoxide, C01937, D00142, EN300-119523, DL-4-Amino-N10-methylpteroylglutamic acid hydrate, Q422232, SR-01000597411, W-60383, (S)-2-(4-(((2,4-diaminopteridin-6-yl)methyl), Q-201366, SR-01000075682-1, SR-01000075682-2, SR-01000075682-6, SR-01000597411-1, W-105347, BRD-K59456551-001-09-3, BRD-K59456551-001-11-9, WLN: T66 BN DN GN JNJ CZ EZ H1N1&R DVMYVQ2VQ, Z1521553982, 4-AMINO-4-DEOXY-N(SUP 10)-METHYLPTEROYLGLUTAMATE, Methotrexate, European Pharmacopoeia (EP) Reference Standard, Methotrexate, United States Pharmacopeia (USP) Reference Standard, Glutamic acid,4-diamino-6-pteridinyl)methyl] methylamino]benzoyl]-, L-(+)-, L-Glutamic acid,4-diamino-6-pteridinyl)methyl]- methylamino]benzoyl]-, (S)-2-(4-(((2,4-Diaminopteridin-6-yl)methyl)-(methyl)amino)benzamido)pentanedioic acid, GLUTAMIC ACID, N-(P-(((2,4-DIAMINO-6-PTERIDINYL)METHYL)METHYLAMINO)BENZOYL)-,L, L-Glutamic acid,N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-,hydrate(9ci), Methotrexate for peak identification, European Pharmacopoeia (EP) Reference Standard, Methotrexate for system suitability, European Pharmacopoeia (EP) Reference Standard, Methotrexate, Pharmaceutical Secondary Standard; Certified Reference Material, N-(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}benzoyl)-L-glutamic acid, N-[4-[[(2,4-Diamino-6-pteridinyl)methyl] methylamino]benzoyl]-L-glutamic acid, (2S)-2-((4-(((2,4-DIAMINOPTERIDIN-6-YL)METHYL)(METHYL)AMINO)BENZOYL)AMINO)PENTANEDIOIC ACID, (2S)-2-[[[4-[(2,4-diamino-6-pteridinyl)methyl-methylamino]phenyl]-oxomethyl]amino]pentanedioic acid;hydrate, (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methyl-amino]benzoyl]amino]glutaric acid;hydrate, (2S)-2-[[4-[[2,4-bis(azanyl)pteridin-6-yl]methyl-methyl-amino]phenyl]carbonylamino]pentanedioic acid;hydrate, 102613-64-9

Name	Methotrexate
PubChem CID	126941
Molecular Weight	454.4g/mol
Synonyms	methotrexate, 59-05-2, Rheumatrex, Amethopterin, Methylaminopterin, Metatrexan, Hdmtx, Abitrexate, Trexall, Mexate, Ledertrexate, Methylaminopterinum, (S)-2-(4-(((2,4-Diaminopteridin-6-yl)methyl)(methyl)amino)benzamido)pentanedioic acid, Methotrexatum, Antifolan, MTX, 4-Amino-10-methylfolic acid, Amethopterine, Metotrexato, Emtexate, Maxtrex, Rasuvo, Methotrexate hydrate, A-Methopterin, L-Amethopterin, A-Methpterin, Amethopterin L-, Folex-Pfs, Methotrexat-Ebewe, NSC-740, Methotrexate, L-, N-Bismethylpteroylglutamic acid, Farmitrexat, Medsatrexate, Methoblastin, Methotextrate, Methotrexat, Metotressato, Brimexate, Emthexat, Emthexate, Fauldexato, Lantarel, Lumexon, Metrotex, Novatrex, Otrexup, Tremetex, Trexeron, Trixilem, Texate, Metex, Mexate-Aq, alpha-Methopterin, CL-14377, Folex, NCI-C04671, JYLAMVO, Methotrexate Lpf, CCRIS 1109, Nordimet, Xatmep, EMT 25,299, 133073-73-1, 4-Aminomethylpteroylglutamic acid, HSDB 3123, NSC 740, CL 14377, UNII-YL5FZ2Y5U1, Methotrexatum [INN-Latin], Metotrexato [INN-Spanish], EINECS 200-413-8, YL5FZ2Y5U1, R 9985, REDITREX, NSC740, DTXSID4020822, CHEBI:44185, AI3-25299, TCMDC-125858, X 133, 4-Amino-N(sup 10)-methylpteroylglutamic acid, ADX-2191, MPI-2505, WR-19039, CHEMBL34259, DTXCID80822, (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]pentanedioic acid, R-9985, Kyselina 4-amino-N(sup 10)-methylpteroylglutamova, N-(p-(((2,4-Diamino-6-pteridyl)methyl)methylamino)benzoyl)glutamic acid, L-(+)-N-(p-(((2,4-Diamino-6-pteridinyl)methyl)methylamino)benzoyl)glutamic acid, N-(4-(((2,4-Diamino-6-pteridinyl)methyl)methylamino)benzoyl)-L-glutamicacid, N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid, N-(p-(((2,4-Diamino-6-pteridinyl)methyl)methylamino)benzoyl)-L-(+)-glutamic acid, N-[(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}phenyl)carbonyl]-L-glutamic acid, Methotrexate [USAN:USP:INN:BAN:JAN], NCGC00025060-04, 4-amino-N(10)-methylpteroylglutamic acid, MFCD00150847, Kyselina N-(p-((2,4-diamino-6-pteridinylmethyl)methylamino)benzoyl)-L-glutamova, METHOTREXATE (IARC), METHOTREXATE [IARC], Methotrexatum (INN-Latin), Metotrexato (INN-Spanish), (2S)-2-[(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}phenyl)formamido]pentanedioic acid, Glutamic acid, N-(p-(((2,4-diamino-6-pteridinyl)methyl)methylamino)benzoyl)-, L-, METHOTREXATE (MART.), METHOTREXATE [MART.], METHOTREXATE (USP-RS), METHOTREXATE [USP-RS], Metotressato [DCIT], Methotrexate, d-, METHOTREXATE (EP MONOGRAPH), METHOTREXATE (USP IMPURITY), METHOTREXATE [EP MONOGRAPH], METHOTREXATE [USP IMPURITY], METHOTREXATE (USP MONOGRAPH), METHOTREXATE [USP MONOGRAPH], MLS001401431, [3H]methotrexate, Methotrexate (hydrate), Methotrexate (USAN:USP:INN:BAN:JAN), SMR000112001, [3H]-methotrexate, folic acid antagonist, 4-Amino-10-methylfolic acid hydrate, SR-01000075682, SMR000449324, Methotrexate (1.0mg/mL in Methanol with 0.1N NaOH), TCMDC-125488, Metolate, Antifolan hydrate, Intradose-MTX, MTX hydrate, 1dhi, 1dhj, 2drc, 4ocx, (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methyl-amino]benzoyl]amino]pentanedioic acid, CAS-59-05-2, Prestwick_322, Otrexup (TN), Xatmep (TN), L-METHOTREXATE, OTREXUP PFS, Kyselina 4-amino-N(sup 10)-methylpteroylglutamova [Czech], Methylaminopterin; MTX, DL-Amethopterin hydrate, Spectrum_001836, Tocris-1230, 4kn0, Methylaminopterin hydrate, Prestwick0_000135, Prestwick1_000135, Prestwick2_000135, Spectrum2_001077, Spectrum3_000497, Spectrum4_000616, Spectrum5_000958, Abitrexate (Methotrexate), METHOTREXATE [MI], METHOTREXATE [INN], METHOTREXATE [JAN], METHOTREXATE [HSDB], METHOTREXATE [USAN], NCIMech_000767, SCHEMBL3711, Kyselina N-(p-((2,4-diamino-6-pteridinylmethyl)methylamino)benzoyl)-L-glutamova [Czech], METHOTREXATE [VANDF], BIDD:PXR0175, Lopac0_000020, KBioGR_001172, KBioSS_002341, Methotrexate Methylaminopterin, MLS000049968, MLS002154208, DivK1c_000114, METHOTREXATE [WHO-DD], METHOTREXATE [WHO-IP], SPBio_001094, SPBio_002149, Amethopterin (hydrate); CL14377 (hydrate); WR19039 (hydrate), AMY235, cid_126941, cid_165528, GTPL4674, GTPL4815, SCHEMBL12421860, SCHEMBL23111732, BDBM18050, BDBM66082, HMS500F16, KBio1_000114, KBio2_002338, KBio2_004906, KBio2_007474, KBio3_001493, Methotrexate (JP17/USP/INN), L01BA01, L04AX03, g301, NINDS_000114, Bio1_000486, Bio1_000975, Bio1_001464, HMS1568K12, HMS2095K12, HMS2233O18, HMS3260C21, HMS3414L09, HMS3678L07, HMS3712K12, METHOTREXATE [ORANGE BOOK], APC-2002, BCP13701, GLUTAMIC ACID, N-(P-(((2,4-DIAMINO-6-PTERIDINYL)METHYL)METHYLAMINO)BENZOYL)-, L-(+)-, MPI-5004, Tox21_110944, Tox21_300269, Tox21_500020, CCG-35800, EMT-25299, METHOTREXATUM [WHO-IP LATIN], MFCD00064370, s1210, STL535338, (4-(((2,4-diaminopteridin-6-yl)methyl)(methyl)amino)benzoyl)-L-glutamic acid, AKOS016340329, Tox21_110944_1, CL14377, CS-1732, DB00563, KS-5093, LP00020, SDCCGSBI-0050009.P003, IDI1_000114, SMP2_000020, (methyl)amino)benzamido)pentanedioic acid, NCGC00025060-01, NCGC00025060-02, NCGC00025060-03, NCGC00025060-05, NCGC00025060-06, NCGC00025060-07, NCGC00025060-08, NCGC00025060-09, NCGC00025060-10, NCGC00025060-11, NCGC00025060-12, NCGC00025060-13, NCGC00025060-15, NCGC00025060-16, NCGC00254216-01, NCGC00260705-01, HY-14519, EU-0100020, FT-0601523, FT-0630651, G-301, NS00098764, SW198601-3, Methotrexate 1.0 mg/ml in Dimethyl Sulfoxide, C01937, D00142, EN300-119523, DL-4-Amino-N10-methylpteroylglutamic acid hydrate, Q422232, SR-01000597411, W-60383, (S)-2-(4-(((2,4-diaminopteridin-6-yl)methyl), Q-201366, SR-01000075682-1, SR-01000075682-2, SR-01000075682-6, SR-01000597411-1, W-105347, BRD-K59456551-001-09-3, BRD-K59456551-001-11-9, WLN: T66 BN DN GN JNJ CZ EZ H1N1&R DVMYVQ2VQ, Z1521553982, 4-AMINO-4-DEOXY-N(SUP 10)-METHYLPTEROYLGLUTAMATE, Methotrexate, European Pharmacopoeia (EP) Reference Standard, Methotrexate, United States Pharmacopeia (USP) Reference Standard, Glutamic acid,4-diamino-6-pteridinyl)methyl] methylamino]benzoyl]-, L-(+)-, L-Glutamic acid,4-diamino-6-pteridinyl)methyl]- methylamino]benzoyl]-, (S)-2-(4-(((2,4-Diaminopteridin-6-yl)methyl)-(methyl)amino)benzamido)pentanedioic acid, GLUTAMIC ACID, N-(P-(((2,4-DIAMINO-6-PTERIDINYL)METHYL)METHYLAMINO)BENZOYL)-,L, L-Glutamic acid,N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-,hydrate(9ci), Methotrexate for peak identification, European Pharmacopoeia (EP) Reference Standard, Methotrexate for system suitability, European Pharmacopoeia (EP) Reference Standard, Methotrexate, Pharmaceutical Secondary Standard; Certified Reference Material, N-(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}benzoyl)-L-glutamic acid, N-[4-[[(2,4-Diamino-6-pteridinyl)methyl] methylamino]benzoyl]-L-glutamic acid, (2S)-2-((4-(((2,4-DIAMINOPTERIDIN-6-YL)METHYL)(METHYL)AMINO)BENZOYL)AMINO)PENTANEDIOIC ACID, (2S)-2-[[[4-[(2,4-diamino-6-pteridinyl)methyl-methylamino]phenyl]-oxomethyl]amino]pentanedioic acid;hydrate, (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methyl-amino]benzoyl]amino]glutaric acid;hydrate, (2S)-2-[[4-[[2,4-bis(azanyl)pteridin-6-yl]methyl-methyl-amino]phenyl]carbonylamino]pentanedioic acid;hydrate, 102613-64-9
Drug Type	Small molecule
Formula	C₂₀H₂₂N₈O₅
SMILES	CN(CC1=CN=C2C(=N1)C(=NC(=N2)N)N)C3=CC=C(C=C3)C(=O)NC(CCC(=O)O)C(=O)O
InChI	1S/C20H22N8O5/c1-28(9-11-8-23-17-15(24-11)16(21)26-20(22)27-17)12-4-2-10(3-5-12)18(31)25-13(19(32)33)6-7-14(29)30/h2-5,8,13H,6-7,9H2,1H3,(H,25,31)(H,29,30)(H,32,33)(H4,21,22,23,26,27)/t13-/m0/s1
InChIKey	FBOZXECLQNJBKD-ZDUSSCGKSA-N
CAS Number	59-05-2
ChEMBL ID	CHEMBL34259
ChEBI ID	CHEBI:44185
TTD ID	D0SV8E
Drug Bank ID	DB00563
KEGG ID	C01937
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	Vitamin C, Methotrexate
Partner Name	Vitamin C
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G2/M phase
Gene Regulation	Up-regulation	Cleavage	CASP3	hsa836
Gene Regulation	Up-regulation	Phosphorylation	MAPK14	hsa1432
In Vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
Result	Combined low-dose vitamin C and MTX had synergistic anti-proliferative/cytotoxic effects on TNBC cells. In addition, co-treatment increased H2O2 levels and activated both caspase-3 and p38 cell death pathways.

Pair Name	Thymoquinone, Methotrexate
Partner Name	Thymoquinone
Disease Info	[ICD-11: 2B51]	Osteosarcoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Expression	CASP3	hsa836
In Vitro Model	SaOS-2	Osteosarcoma	Homo sapiens (Human)	CVCL_0548
Result	The findings of the present study highlight new insights into understanding the role of TQ as a potential therapeutic agent in osteosarcoma by increasing MTX-induced apoptosis.

Pair Name	Thymoquinone, Methotrexate
Partner Name	Thymoquinone
Disease Info	[ICD-11: 2B51]	Osteosarcoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Expression	CASP9	hsa842
In Vitro Model	SaOS-2	Osteosarcoma	Homo sapiens (Human)	CVCL_0548
Result	The co-treatment of TQ and MTX is associated with the up-regulation of apoptotic factors and down-regulation of anti-apoptotic factors, conducting apoptosis aggravation and OS cell death.

Pair Name	Shogaol, Methotrexate
Partner Name	Shogaol
Disease Info	[ICD-11: 2B33.3]	Acute lymphoblastic leukemia		Investigative
Biological Phenomena	Induction-->ROS generation
Gene Regulation	Up-regulation	Expression	BBC3	hsa27113
	Up-regulation	Expression	CDKN1A	hsa1026
	Down-regulation	Expression	FASN	hsa2194
	Up-regulation	Expression	TP53	hsa7157
In Vivo Model	Four‐ to six‐week‐old female athymic nude mice (C57BL/6 nude) were injected with 1.5×10⁷ CCRF‐CEM cells in 100 μL FBS, subcutaneously. In order to confirm leukaemia engraftment, flow cytometry was performed on mice blood samples by using antibodies against CCRF‐CEM cell‐line CD markers.
Result	The current study revealed the in vivo novel anti-leukaemic role of ginger extract, promoted by MTX. Moreover, 6-shogaol was introduced as the major player of ginger cytotoxicity through inducing p53 activity and ROS generation.

Pair Name	Paeonol, Methotrexate
Partner Name	Paeonol
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	ABCB1	hsa5243
	Down-regulation	Expression	CASP3	hsa836
	Down-regulation	Expression	IL1B	hsa3553
	Down-regulation	Expression	NFKB1	hsa4790
	Down-regulation	Expression	TLR4	hsa7099
In Vitro Model	HCT 116	Colon carcinoma	Homo sapiens (Human)	CVCL_0291
In Vivo Model	Male Wistar rats weighing 180–220 g were used in study.
Result	Paeonol protects against MTX-induced nephrotoxicity through antioxidant, anti-inflammatory, and antiapoptotic mechanisms and might potentiate MTX chemotherapeutic efficacy.

Pair Name	Chlorogenic acid, Methotrexate
Partner Name	Chlorogenic acid
Disease Info	[ICD-11: 2B33.4]	Leukemia		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP9	hsa842
	Down-regulation	Expression	COX2	hsa4513
	Down-regulation	Expression	GPT	hsa2875
	Down-regulation	Expression	LDHA	hsa3939
	Down-regulation	Expression	NOS2	hsa4843
In Vivo Model	6-8 weeks old Male Wistar rats (150-200 g) were use in this study.
Result	These results imply that CGA has perfective effect against MTX-induced liver injury. Hence CGA supplementation might be helpful in abrogation of MTX toxicity.

No.	Title	Href
1	Paeonol Protects Against Methotrexate-Induced Nephrotoxicity via Upregulation of P-gp Expression and Inhibition of TLR4/NF-κB Pathway. Front Pharmacol. 2022 Feb 4;13:774387. doi: 10.3389/fphar.2022.774387.	`Click`
2	Protective effect of Chlorogenic acid against methotrexate induced oxidative stress, inflammation and apoptosis in rat liver: An experimental approach. Chem Biol Interact. 2017 Jun 25;272:80-91. doi: 10.1016/j.cbi.2017.05.002.	`Click`
3	Combined treatment with vitamin C and methotrexate inhibits triple-negative breast cancer cell growth by increasing H2O2 accumulation and activating caspase-3 and p38 pathways. Oncol Rep. 2017 Apr;37(4):2177-2184. doi: 10.3892/or.2017.5439.	`Click`
4	Thymoquinone Potentiates Methotrexate Mediated-Apoptosis in Saos-2 Osteosarcoma Cell Line. Drug Res (Stuttg). 2022 Sep;72(7):390-395. doi: 10.1055/a-1842-7545.	`Click`
5	Thymoquinone Augments Methotrexate-Induced Apoptosis on Osteosarcoma Cells. Drug Res (Stuttg). 2022 Apr;72(4):220-225. doi: 10.1055/a-1775-7908.	`Click`
6	6-Shogaol induces apoptosis in acute lymphoblastic leukaemia cells by targeting p53 signalling pathway and generation of reactive oxygen species. J Cell Mol Med. 2021 May 3;25(13):6148–60. doi: 10.1111/jcmm.16528.	`Click`