Screening of traditional Chinese medicine monomers as ribonucleotide reductase M2 inhibitors for tumor treatment

Table 1 Tumor abbreviations

Abbreviation	Full name	Abbreviation	Full name	Abbreviation	Full name
ACC	Adrenocortical carcinoma	BLCA	Bladder Urothelial Carcinoma	BRCA	Breast invasive carcinoma
CESC	Cervical squamous cell carcinoma and endocervical adenocarcinoma	CHOL	Cholangio carcinoma	COAD	Colon adenocarcinoma
DLBC	Lymphoid Neoplasm Diffuse Large B-cell Lymphoma	ESCA	Esophageal carcinoma	GBM	Glioblastoma multiforme
HNSC	Head and Neck squamous cell carcinoma	KICH	Kidney Chromophobe	KIRC	Kidney renal clear cell carcinoma
KIRP	Kidney renal papillary cell carcinoma	LAML	Acute Myeloid Leukemia	LGG	Brain Lower Grade Glioma
LIHC	Liver hepatocellular carcinoma	LUAD	Lung adenocarcinoma	LUSC	Lung squamous cell carcinoma
MESO	Mesothelioma	OV	Ovarian serous cystadenocarcinoma	PAAD	Pancreatic adenocarcinoma
PCPG	Pheochromocytoma and Paraganglioma	PRAD	Prostate adenocarcinoma	READ	Rectum adenocarcinoma
SARC	Sarcoma	SKCM	Skin Cutaneous Melanoma	STAD	Stomach adenocarcinoma
UCEC	Uterine Corpus Endometrial Carcinoma	UCS	Uterine Carcinosarcoma	UVM	Uveal Melanoma
TGCT	Testicular Germ Cell Tumors	THCA	Thyroid carcinoma	THYM	Thymoma

Table 2 The traditional Chinese medicine monomers confirmed or predicted having ribonucleotide reductase M2 inhibition in tumors

Name	In vivo study	In vitro study	Bioinformatics analysis
Berberine	-	Non-small cell lung cancer	Breast cancer
Ursolic acid	-	-	Hepatoma, Colon cancer
Gambogic acid	Pancreatic cancer	Pancreatic cancer	-
Cinobufagin	Endometrial carcinoma	Endometrial carcinoma	-
Quercetin	-	-	Hepatoma, Colon cancer
Daphnetin	-	-	-
Osalmide	Esophageal Cancer, Multiple myeloma, Hepatocellular carcinoma, Diffuse large B-cell lymphoma	Esophageal Cancer, Multiple myeloma, Hepatocellular carcinoma, Diffuse large B-cell lymphoma	Multiple myeloma, Hepatocellular carcinoma

Table 3 The binding energy and binding sites of the selected traditional Chinese medicine monomers with ribonucleotide reductase M2

Names	Binding energy	Hydrogen bond site	Hydrophobic bond site
Berberine	-7.3 kcal/mol	Ser263 (A)	Glu260(A), Arg264(A), Tyr323(A), Arg330(A), Gly233(A), Val327(A), Ser237(A), and Gly267(A)
Ursolic acid	-8.6 kcal/mol	-	Arg264(A), Gly267(A), Cys270(A), Gly233(A), Arg330(A), Val327(A), Ser263(A), Phe244(A), Phe349(A), and Met350(A)
Gambogic acid	-8.6 kcal/mol	Arg330(A) and Tyr323(A)	Gly267(A), Leu268(A), Ser100(A), Lys96(A), Arg264(A), Met350(A), and Ser263(A)
Cinobufagin	-7.6 kcal/mol	Asp271 (A) and Arg330 (A)	Glu334 (A), Leu331 (A), Cys270 (A), Gly267 (A), Glu266 (A), Ser263 (A), Phe244 (A), and Met350 (A)
Quercetin	-7.4 kcal/mol	Arg330 (A) and Tyr323 (A)	Met350 (A), Arg264 (A), Glu260 (A), Phe244 (A), Ser263 (A), Glu232 (A), Gly233 (A), Phe240 (A) and Val327 (A)
Daphnetin	-6.7 kcal/mol	Tyr323 (A) and Arg330 (A)	Val327 (A), Ser263 (A), Phe240 (A), Met350 (A), Gly267 (A), Gly233 (A), and Gys270 (A)
Osalmide	-6.8 kcal/mol	-	Phe244 (A), Arg264 (A), Tyr323 (A), Phe240 (A), Ser237 (A), Met350 (A), Gly233 (A), and Ser263 (A)