RRM1

Summary

RRM1 (ribonucleotide reductase catalytic subunit M1, HGNC:10451) is a protein-coding gene on chromosome 11p15.4, encoding Ribonucleoside-diphosphate reductase large subunit (P23921). Provides the precursors necessary for DNA synthesis. In precision oncology, RRM1 Underexpression confers sensitivity to Gemcitabine + Cisplatin in Lung Non-small Cell Carcinoma (CIViC Level B); 8 further curated variant–drug associations are listed below. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

This gene encodes the large and catalytic subunit of ribonucleotide reductase, an enzyme essential for the conversion of ribonucleotides into deoxyribonucleotides. A pool of available deoxyribonucleotides is important for DNA replication during S phase of the cell cycle as well as multiple DNA repair processes. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 6240 — RefSeq curated summary.

At a glance

• Gene–disease (curated): progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 6 (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 12
• Clinical variants (ClinVar): 84 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 67
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 9 curated variant–drug associations
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_001033

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10451
Approved symbol	RRM1
Name	ribonucleotide reductase catalytic subunit M1
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000167325
Ensembl biotype	protein_coding
OMIM	180410
Entrez	6240

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 4 protein_coding, 4 protein_coding_CDS_not_defined, 4 retained_intron, 4 nonsense_mediated_decay

ENST00000300738, ENST00000526304, ENST00000526350, ENST00000526865, ENST00000528442, ENST00000528470, ENST00000529109, ENST00000530368, ENST00000531591, ENST00000532170, ENST00000532710, ENST00000533349, ENST00000533495, ENST00000534285, ENST00000854928, ENST00000854929

RefSeq mRNA: 4 — MANE Select: NM_001033 NM_001033, NM_001318064, NM_001318065, NM_001330193

CCDS: CCDS7750, CCDS81547

Canonical transcript exons

ENST00000300738 — 19 exons

Exon	Start	End
ENSE00001838070	4138195	4138932
ENSE00002153098	4094799	4095031
ENSE00003493610	4107435	4107535
ENSE00003539380	4111601	4111640
ENSE00003560199	4106046	4106223
ENSE00003560908	4109644	4109703
ENSE00003561495	4133563	4133658
ENSE00003580075	4119845	4119928
ENSE00003589547	4101993	4102081
ENSE00003594495	4129074	4129150
ENSE00003596042	4135082	4135270
ENSE00003617237	4111900	4112062
ENSE00003633973	4123183	4123384
ENSE00003637542	4122141	4122220
ENSE00003639050	4121604	4121765
ENSE00003639634	4127035	4127256
ENSE00003663342	4118320	4118461
ENSE00003666985	4132286	4132421
ENSE00003686240	4126684	4126833

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 98.29.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 64.2022 / max 1044.0370, expressed in 1813 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112764	43.6391	1798
112763	19.1788	1779
112762	0.8833	551
112767	0.5011	265

Top tissues by expression

299 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.29	gold quality
ganglionic eminence	UBERON:0004023	97.89	gold quality
cervix squamous epithelium	UBERON:0006922	97.42	gold quality
embryo	UBERON:0000922	97.04	gold quality
penis	UBERON:0000989	96.95	gold quality
nipple	UBERON:0002030	96.73	gold quality
tongue squamous epithelium	UBERON:0006919	96.48	gold quality
trabecular bone tissue	UBERON:0002483	96.40	gold quality
skin of hip	UBERON:0001554	96.34	gold quality
upper leg skin	UBERON:0004262	96.09	gold quality
pharyngeal mucosa	UBERON:0000355	95.97	gold quality
mammalian vulva	UBERON:0000997	95.85	gold quality
calcaneal tendon	UBERON:0003701	95.62	gold quality
hair follicle	UBERON:0002073	95.32	gold quality
gingival epithelium	UBERON:0001949	95.19	gold quality
tendon	UBERON:0000043	95.07	gold quality
gingiva	UBERON:0001828	95.06	gold quality
epithelium of nasopharynx	UBERON:0001951	94.87	gold quality
nasopharynx	UBERON:0001728	94.85	gold quality
stromal cell of endometrium	CL:0002255	94.71	gold quality
superior surface of tongue	UBERON:0007371	94.34	gold quality
oral cavity	UBERON:0000167	94.33	gold quality
squamous epithelium	UBERON:0006914	94.31	gold quality
bone marrow	UBERON:0002371	94.21	gold quality
pylorus	UBERON:0001166	93.84	gold quality
cervix epithelium	UBERON:0004801	93.76	gold quality
amniotic fluid	UBERON:0000173	93.61	gold quality
tongue	UBERON:0001723	93.55	gold quality
adrenal tissue	UBERON:0018303	93.42	gold quality
secondary oocyte	CL:0000655	93.32	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-6075	yes	320.44
E-HCAD-10	yes	34.87
E-CURD-122	yes	22.38
E-ANND-3	yes	8.49
E-MTAB-6678	yes	7.72
E-MTAB-10553	yes	7.01
E-MTAB-9801	yes	3.56
E-GEOD-99795	no	577.83
E-CURD-10	no	401.75
E-MTAB-6058	no	381.82
E-GEOD-76312	no	287.43
E-MTAB-7037	no	212.73
E-CURD-88	no	3.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, E2F4, HR, KAT5, SP1, TFDP1, THAP1, TP53

miRNA regulators (miRDB)

21 targeting RRM1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-4705	99.10	69.10	1091
HSA-MIR-605-5P	98.79	68.24	1161
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-10526-3P	97.86	64.97	1342
HSA-MIR-4733-5P	97.75	67.44	866
HSA-MIR-6894-3P	96.73	65.64	798
HSA-MIR-6782-5P	96.45	64.42	612
HSA-MIR-3619-3P	95.59	65.99	428

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• overexpression of RRM1 in human and mouse lung cancer cell lines induced PTEN expression, reduced phosphorylation of focal adhesion kinase (FAK), suppressed migration, invasion, and metastasis formation, and increased survival in an animal model. (PMID:12687015)
• RRM1 levels influenced time to progression (P=0.05) and even more so, survival (P=0.0028) in the gemcitabine/cisplatin arm (PMID:12789263)
• Susceptibility differences to RR inhibitors between hRRM1 and hRRM2 may lead to a new direction in drug design for human cancer treatment. (PMID:14729598)
• The level of RRM1 may affect gemcitabine response in non-small cell lung cancer. Furthermore, RRM1 may serve as a biomarker for gemcitabine response. (PMID:15172981)
• the binding site on RRM1 demonstrated higher affinity for RRM2 subunit than for p53R2 subunit (PMID:16376858)
• overexpressed during the S phase of the cell cycle compared with the G0/1 phase (PMID:16476973)
• Motexafin gadolinium induces enzymatic generation of reactive oxygen species by thioredoxin reductase and inhibits ribonucleotide reductase (PMID:16481328)
• results strongly suggest that tumoral RRM1 expression is a major predictor of disease response to gemcitabine/platinum chemotherapy (PMID:16966686)
• RRM1 could play a role in the prediction of patient outcome, and draw attention to the fact that response to gemcitabine. (PMID:17064812)
• RRM1 RNA expression has a role in acquired resistance to gemcitabine (PMID:17065054)
• RRM1 should be a key molecule in gemcitabine resistance in human pancreatic cancer. (PMID:17131328)
• RRM1 haplotype showed an association with susceptibility to gemcitabine monotherapy in breast cancer patients. (PMID:17602053)
• Ribonucleotide reductase subunit M1(RRM1) mRNA expression in lung adenocarcinoma is associated with clinical outcome of docetaxel/gemcitabine therapy. (PMID:18414411)
• significant differences in response rates to gemcitabine-based chemotherapy according to the allelotypes of the RRM1 promoter sequence (PMID:18483375)
• Significantly higher RRM1 mRNA expression was found in SCLC compared with NSCLC. There was no correlation between mRNA expression of the RRM1 gene and chemosensitivity to cisplatin, carboplatin or gemcitabine. (PMID:18494946)
• Expression of RRM1 is associated with chemoresistance marker to gemcitabine in biliary tract carcinoma (PMID:18636187)
• The mRNA expression of RRM1 is potentially a useful tool for selecting NSCLC patients for individualized chemotherapy (PMID:19002265)
• genetic polymorphisms is associated with sensitivity to platin-based chemotherapy in non-small cell lung cancer patients (PMID:19304340)
• Data show that the combination of RRM1 and ERCC1 expression is prognostic in pancreatic cancer patients after a complete resection. (PMID:19543324)
• patients with advanced NSCLC treated with chemotherapy with gemcitabine and cisplatin appear to have a poor outcome if the tumor express elevated levels of RRM1 gene but surgical resection shows better survival. (PMID:19552012)
• Esophageal squamous cell carcinoma cells with a lower level of RRM1 expression are more sensitive to gemcitabine. (PMID:20021860)
• RRM1 suppression is an important step in increasing Gemcitabine efficacy (PMID:20043067)
• Tip60-dependent recruitment of RNR plays an essential role in dNTP supply for DNA repair (PMID:20159953)
• Compared with their parental cells, the expressions of CDA, RRM1, PTEN and ERCC1 increase in human gemcitabine-resistant non-small cell lung cancer cell lines. (PMID:20211060)
• RRM1 single nucleotide polymorphism is not associated with non-small cell lung cancer patients after gemcitabine-based chemotherapy. (PMID:20226083)
• ERCC1, RRM1 and BRCA1 are promising predictive and prognostic biomarkers in advanced non-small cell lung cancer. (PMID:20467918)
• RRM1, particularly in protein, level is a reliable marker for gemcitabine resistance in biliary tract carcinoma. (PMID:20811706)
• In postoperative NSCLC patients who are receiving adjuvant chemotherapy, patients with high expression of RRM1 tend to be resistant to gemcitabine. (PMID:20868593)
• RRM1 -37A>C polymorphism may represent a useful biomarker to select mCRC patients most likely to benefit from gemcitabine-based salvage therapy. (PMID:21220199)
• M1 (RRM1) expression in resected pancreatic cancer is not associated with OS or Pfs. (PMID:21264835)
• The study reports the first X-ray structures of human RR1 bound to TTP alone, dATP alone, TTP-GDP, TTP-ATP, and TTP-dATP. (PMID:21336276)
• RRM1 has a role in response to gemcitabine plus platinum therapy in advanced non-small-cell lung cancer (PMID:21370501)
• Cases with EGFR overexpression showed high expression of RRM1 and BRCA1 (PMID:21394302)
• The RRM1 2464 A/G, RRM1 37 C/C and RRM1 524 T/T alleles were associated with statistically significant superior progression free survival in pancreatic cancer patients receiving combination gemcitabine and sorafenib (PMID:21424698)
• Data suggest ribonucleotide reductase A site binding with inhibitor. (PMID:21628579)
• Single-nucleotide polymorphisms in RRM1 gene is associated with treatment response in non-small cell lung cancer. (PMID:21642870)
• RRM1 polymorphisms as well as haplotypes showed an association with gemcitabine treatment efficacy and toxicity. (PMID:22134350)
• RRM1 levels in pancreatic ductal adenocarcinoma did not predict survival times in patients treated with adjuvant gemcitabine. (PMID:22705007)
• The expression of RRMI and ERCC1 genes in tumor tissues and RRM1 in peripheral blood lymphocytes is closely correlated with the response to chemotherapy and prognosis of patients with advanced non-small cell lung cancer. (PMID:23086647)
• We assessed the relation of mRNA levels of ERCC1, RRM1, and BRCA1 to survival in surgically-resected tumor tissues from patients who underwent adjuvant chemotherapy (PMID:23155271)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rrm1	ENSDARG00000014017
mus_musculus	Rrm1	ENSMUSG00000030978
rattus_norvegicus	Rrm1	ENSRNOG00000045752
drosophila_melanogaster	RnrL	FBGN0011703
caenorhabditis_elegans		WBGENE00004391

Protein

Protein identifiers

Ribonucleoside-diphosphate reductase large subunit — P23921 (reviewed: P23921)

Alternative names: Ribonucleoside-diphosphate reductase subunit M1, Ribonucleotide reductase large subunit

All UniProt accessions (6): P23921, E9PJ62, E9PL69, E9PP77, E9PRY9, H0YCY7

UniProt curated annotations — full annotation on UniProt →

Function. Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.

Subunit / interactions. Heterodimer of a large and a small subunit. Heterodimer with small subunit RRM2 or RRM2B. The heterodimer with RRM2 has higher catalytic activity than the heterodimer with RRM2B. Interacts with AHCYL1 which inhibits its activity.

Subcellular location. Cytoplasm.

Disease relevance. Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 6 (PEOB6) [MIM:620647] A form of progressive external ophthalmoplegia, a mitochondrial myopathy characterized by progressive paralysis of the levator palpebrae, orbicularis oculi, and extraocular muscles. Ragged red fibers are seen on muscle biopsy. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding to separate specificity and activation sites on the M1 subunit. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction and dTTP favors GDP reduction. Stimulated by ATP and inhibited by dATP binding to the activity site, the dATP inhibition is mediated by AHCYL1 which stabilizes dATP in the site.

Miscellaneous. Two distinct regulatory sites have been defined: the specificity site, which controls substrate specificity, and the activity site which regulates overall catalytic activity. A substrate-binding catalytic site, located on M1, is formed only in the presence of the second subunit M2. The level of the enzyme activity is closely correlated with the growth rate of a cell and appears to vary with the cell cycle.

Similarity. Belongs to the ribonucleoside diphosphate reductase large chain family.

RefSeq proteins (4): NP_001024, NP_001304993, NP_001304994, NP_001317122 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000788	RNR_lg_C	Domain
IPR005144	ATP-cone_dom	Domain
IPR008926	RNR_R1-su_N	Homologous_superfamily
IPR013346	NrdE_NrdA_C	Domain
IPR013509	RNR_lsu_N	Domain
IPR039718	Rrm1	Family

Pfam: PF00317, PF02867, PF03477

Enzyme classification (BRENDA):

• EC 1.17.4.1 — ribonucleoside-diphosphate reductase (BRENDA: 56 organisms, 130 substrates, 474 inhibitors, 39 Km, 9 kcat entries)

Substrate kinetics (BRENDA)

10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CDP	0.0005–0.31	14
ADP	0.0078–0.3	6
GDP	0.0012–0.37	4
UDP	0.08–1.2	4
ATP	0.07	1
DATP	0.003	1
DTTP	0.0015	1
GLUTAREDOXIN	0.0001	1
GLUTAREDOXIN 1	0.006	1
THIOREDOXIN	0.003	1

Catalyzed reactions (Rhea), 1 shown:

• a 2’-deoxyribonucleoside 5’-diphosphate + [thioredoxin]-disulfide + H2O = a ribonucleoside 5’-diphosphate + [thioredoxin]-dithiol (RHEA:23252)

UniProt features (114 total): helix 41, strand 31, binding site 13, turn 7, site 6, sequence variant 5, active site 3, modified residue 3, chain 1, domain 1, disulfide bond 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
6L3R	X-RAY DIFFRACTION	2
6L7L	X-RAY DIFFRACTION	2.17
2WGH	X-RAY DIFFRACTION	2.3
3HNC	X-RAY DIFFRACTION	2.41
6LKM	X-RAY DIFFRACTION	2.55
5TUS	X-RAY DIFFRACTION	2.66
3HNE	X-RAY DIFFRACTION	3.11
3HNF	X-RAY DIFFRACTION	3.16
3HND	X-RAY DIFFRACTION	3.21
6AUI	ELECTRON MICROSCOPY	3.3
4X3V	X-RAY DIFFRACTION	3.7
5D1Y	X-RAY DIFFRACTION	9.01

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23921-F1	92.43	0.80

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (9): 218 (important for hydrogen atom transfer); 444 (important for hydrogen atom transfer); 427 (proton acceptor); 737 (important for electron transfer); 738 (important for electron transfer); 787 (interacts with thioredoxin/glutaredoxin); 790 (interacts with thioredoxin/glutaredoxin); 429 (cysteine radical intermediate); 431 (proton acceptor)

Ligand- & substrate-binding residues (13): 217; 226–228; 243; 256; 263–264; 427; 431; 604–607; 5–6; 11–17; 53; 57 …

Post-translational modifications (3): 17, 376, 751

Disulfide bonds (1): 218–444

Mutagenesis-validated functional residues (1):

Position	Phenotype
57	severely decreases interaction with ahcyl1 in the presence of datp.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-499943	Interconversion of nucleotide di- and triphosphates

MSigDB gene sets: 0 (showing top):

GO Biological Process (15): DNA synthesis involved in DNA repair (GO:0000731), pyrimidine nucleobase metabolic process (GO:0006206), mitochondrial DNA replication (GO:0006264), DNA repair (GO:0006281), male gonad development (GO:0008584), ribonucleoside diphosphate metabolic process (GO:0009185), deoxyribonucleotide biosynthetic process (GO:0009263), 2’-deoxyribonucleotide biosynthetic process (GO:0009265), response to ionizing radiation (GO:0010212), positive regulation of G2/M transition of mitotic cell cycle (GO:0010971), cell proliferation in forebrain (GO:0021846), protein heterotetramerization (GO:0051290), retina development in camera-type eye (GO:0060041), positive regulation of G0 to G1 transition (GO:0070318), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087)

GO Molecular Function (10): ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor (GO:0004748), ATP binding (GO:0005524), identical protein binding (GO:0042802), ribonucleoside-diphosphate reductase activity (GO:0061731), disordered domain specific binding (GO:0097718), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), purine nucleotide binding (GO:0017076)

GO Cellular Component (10): nuclear envelope (GO:0005635), mitochondrion (GO:0005739), cytosol (GO:0005829), ribonucleoside-diphosphate reductase complex (GO:0005971), centriolar satellite (GO:0034451), ciliary basal body (GO:0036064), neuronal cell body (GO:0043025), cytoplasm (GO:0005737), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of nucleotides	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
positive regulation of mitotic cell cycle phase transition	2
cytoplasm	2
DNA repair	1
DNA biosynthetic process	1
nucleobase metabolic process	1
pyrimidine-containing compound metabolic process	1
mitochondrion	1
DNA-templated DNA replication	1
mitochondrial DNA metabolic process	1
DNA metabolic process	1
DNA damage response	1
gonad development	1
development of primary male sexual characteristics	1
nucleoside diphosphate metabolic process	1
biosynthetic process	1
deoxyribonucleotide metabolic process	1
nucleotide biosynthetic process	1
2’-deoxyribonucleotide metabolic process	1
deoxyribose phosphate biosynthetic process	1
response to radiation	1
G2/M transition of mitotic cell cycle	1
regulation of G2/M transition of mitotic cell cycle	1
positive regulation of cell cycle G2/M phase transition	1
forebrain development	1
neural precursor cell proliferation	1
protein tetramerization	1
protein heterooligomerization	1
camera-type eye development	1
anatomical structure development	1
G0 to G1 transition	1
regulation of G0 to G1 transition	1
positive regulation of cell cycle process	1
G1/S transition of mitotic cell cycle	1
positive regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
ribonucleoside-diphosphate reductase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1

Protein interactions and networks

STRING

4721 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RRM1	RRM2	P31350	999
RRM1	RRM2B	Q7LG56	996
RRM1	ESRP1	Q6NXG1	831
RRM1	TARDBP	Q13148	821
RRM1	ESRP2	Q9H6T0	820
RRM1	EIF4G1	Q04637	802
RRM1	ERCC1	P07992	773
RRM1	TYMS	P04818	773
RRM1	TOP2A	P11388	771
RRM1	CELF6	Q96J87	763
RRM1	DCK	P27707	753
RRM1	THAP1	Q9NVV9	745
RRM1	HNRNPDL	O14979	735
RRM1	PABPC1	P11940	729
RRM1	CELF3	Q5SZQ8	719

IntAct

76 interactions, top by confidence:

A	B	Type	Score
HRAS	RAF1	psi-mi:“MI:0914”(association)	0.980
RRM1	RRM2	psi-mi:“MI:0407”(direct interaction)	0.850
RRM2	RRM1	psi-mi:“MI:0914”(association)	0.850
RRM2	RRM1	psi-mi:“MI:0915”(physical association)	0.850
TRIM33	TRIM24	psi-mi:“MI:0914”(association)	0.790
RRM1	RRM1	psi-mi:“MI:0915”(physical association)	0.780
RRM1	RRM1	psi-mi:“MI:0407”(direct interaction)	0.780
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PFDN2	POLR3A	psi-mi:“MI:0914”(association)	0.670
RRM1	ZNF655	psi-mi:“MI:0915”(physical association)	0.560
RRM1	GLRX3	psi-mi:“MI:0914”(association)	0.530
KAT5	YEATS4	psi-mi:“MI:0914”(association)	0.530
GPR37	ATE1	psi-mi:“MI:0914”(association)	0.530
PPP1CC	RRM1	psi-mi:“MI:0915”(physical association)	0.370
OTUB1		psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
Cdca8	NAP1L1	psi-mi:“MI:0914”(association)	0.350
Ubr5	SFI1	psi-mi:“MI:0914”(association)	0.350
RNASEH2B	SAP18	psi-mi:“MI:0914”(association)	0.350
Cdkn2aip	SF1	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350

BioGRID (188): RRM1 (Two-hybrid), RRM1 (Affinity Capture-MS), RRM2 (Co-fractionation), RRM1 (Affinity Capture-MS), RRM1 (Synthetic Growth Defect), RRM1 (Proximity Label-MS), RRM1 (Proximity Label-MS), RRM1 (Affinity Capture-MS), RRM1 (Affinity Capture-MS), RRM1 (Affinity Capture-MS), RRM1 (Affinity Capture-MS), RRM1 (Affinity Capture-MS), RRM1 (Affinity Capture-MS), RRM1 (Affinity Capture-MS), RRM1 (Affinity Capture-MS)

ESM2 similar proteins: A0A7H0DN52, A6Q367, O15909, O55716, O61065, O83972, P07071, P07742, P0A5W9, P0C8H8, P0C8H9, P0CG99, P0CH00, P0DSV1, P0DSV2, P12848, P20503, P21524, P21672, P23921, P26685, P32282, P36602, P42491, P43752, P43754, P48591, P50620, P50647, P50648, P55982, P57276, P74240, P79732, P9WH75, Q03604, Q196Z5, Q54Q71, Q5R919, Q6GZT8

Diamond homologs: A0A7H0DN52, E7FHX6, O15909, O55716, O61065, O66503, O83972, O84834, P07742, P08543, P09853, P0C8H7, P0C8H8, P0C8H9, P0DSV1, P0DSV2, P12848, P20503, P21524, P21672, P23921, P26685, P28846, P36602, P42491, P48591, P50642, P50643, P50647, P50648, P55982, P79732, P89462, Q03604, Q54Q71, Q5R919, Q6R7H4, Q6UDJ2, Q76RD8, Q77MS1

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
E2F1	“up-regulates quantity by expression”	RRM1	“transcriptional regulation”
TFDP1	“up-regulates quantity by expression”	RRM1	“transcriptional regulation”
clofarabine	“down-regulates activity”	RRM1	“chemical inhibition”
RRM1	“form complex”	“Ribonucleotide reductase”	binding
RRM2B	“up-regulates activity”	RRM1	binding
CyclinA2/CDK2	“up-regulates activity”	RRM1	phosphorylation
mTORC2	“up-regulates activity”	RRM1	phosphorylation
gemcitabine	“down-regulates activity”	RRM1	“chemical inhibition”
(2R,3S,4S,5R)-2-(6-amino-2-fluoro-9-purinyl)-5-(hydroxymethyl)oxolane-3,4-diol	“down-regulates activity”	RRM1	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 82 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
double-strand break repair	5	13.7×	6e-03
MAPK cascade	6	12.4×	6e-03
DNA damage response	8	5.8×	7e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

84 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	58
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2664486	NM_001033.5(RRM1):c.1141C>T (p.Arg381Cys)	Pathogenic
2444243	NM_001033.5(RRM1):c.1142G>A (p.Arg381His)	Likely pathogenic

SpliceAI

2685 predictions. Top by Δscore:

Variant	Effect	Δscore
11:4096082:GTGGT:G	donor_gain	1.0000
11:4101988:TTTA:T	acceptor_loss	1.0000
11:4101989:TTAG:T	acceptor_loss	1.0000
11:4101990:TA:T	acceptor_loss	1.0000
11:4101991:A:AG	acceptor_gain	1.0000
11:4101991:AGA:A	acceptor_loss	1.0000
11:4101991:AGAT:A	acceptor_gain	1.0000
11:4101992:G:GG	acceptor_gain	1.0000
11:4101992:GA:G	acceptor_gain	1.0000
11:4101992:GAT:G	acceptor_gain	1.0000
11:4101992:GATG:G	acceptor_gain	1.0000
11:4102077:ATCCT:A	donor_gain	1.0000
11:4102078:TCCT:T	donor_gain	1.0000
11:4102079:CCT:C	donor_gain	1.0000
11:4102080:CT:C	donor_gain	1.0000
11:4102081:TGTA:T	donor_loss	1.0000
11:4102082:GTAA:G	donor_gain	1.0000
11:4102083:T:G	donor_loss	1.0000
11:4102086:G:GG	donor_gain	1.0000
11:4106041:T:TA	acceptor_gain	1.0000
11:4106044:A:AG	acceptor_gain	1.0000
11:4106044:AG:A	acceptor_gain	1.0000
11:4106045:G:GA	acceptor_gain	1.0000
11:4106045:GG:G	acceptor_gain	1.0000
11:4106045:GGC:G	acceptor_gain	1.0000
11:4106045:GGCT:G	acceptor_gain	1.0000
11:4106045:GGCTC:G	acceptor_gain	1.0000
11:4106211:A:T	donor_gain	1.0000
11:4106221:GTG:G	donor_gain	1.0000
11:4106222:TG:T	donor_gain	1.0000

AlphaMissense

5257 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:4118324:T:C	F219L	1.000
11:4118326:T:A	F219L	1.000
11:4118326:T:G	F219L	1.000
11:4119900:C:A	A283D	1.000
11:4121610:G:T	G295W	1.000
11:4121611:G:A	G295E	1.000
11:4122144:T:A	W348R	1.000
11:4122144:T:C	W348R	1.000
11:4123345:C:A	N427K	1.000
11:4123345:C:G	N427K	1.000
11:4132330:C:A	A605D	1.000
11:4102035:G:C	R21P	0.999
11:4106104:T:C	L56P	0.999
11:4106106:G:C	D57H	0.999
11:4106107:A:T	D57V	0.999
11:4106118:G:C	A61P	0.999
11:4106119:C:A	A61D	0.999
11:4106170:C:A	A78E	0.999
11:4106176:G:C	R80T	0.999
11:4106176:G:T	R80M	0.999
11:4106187:T:C	S84P	0.999
11:4106201:A:C	K88N	0.999
11:4106201:A:T	K88N	0.999
11:4107450:T:C	L101P	0.999
11:4109672:G:C	R139P	0.999
11:4109674:G:C	D140H	0.999
11:4109675:A:T	D140V	0.999
11:4109696:G:A	G147D	0.999
11:4111605:T:C	L151P	0.999
11:4111611:G:C	R153P	0.999

dbSNP variants (sampled 300 via entrez): RS1000039596 (11:4120662 C>T), RS1000065003 (11:4097113 C>T), RS1000149197 (11:4102435 A>T), RS1000244192 (11:4102274 T>A,C), RS1000260922 (11:4108530 G>A), RS1000292076 (11:4107607 T>G), RS1000367321 (11:4094563 G>A), RS1000466880 (11:4100817 A>T), RS1000512395 (11:4133131 G>A,C), RS1000524242 (11:4098891 G>A), RS1000559180 (11:4132056 G>C), RS1000641225 (11:4107856 T>A), RS1000698726 (11:4095779 G>T), RS1000887073 (11:4113002 A>G), RS1000952021 (11:4119252 T>C)

Disease associations

OMIM: gene MIM:180410 | disease phenotypes: MIM:620647

GenCC curated gene-disease

Disease	Classification	Inheritance
progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 6	Moderate	Autosomal recessive
progressive external ophthalmoplegia with mitochondrial DNA deletions	Limited	Autosomal dominant

Mondo (2): progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 6 (MONDO:0957993), progressive external ophthalmoplegia with mitochondrial DNA deletions (MONDO:0000090)

Orphanet (0):

HPO phenotypes

67 total (30 of 67 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000298	Mask-like facies
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000479	Abnormal retinal morphology
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000544	External ophthalmoplegia
HP:0000602	Ophthalmoplegia
HP:0000648	Optic atrophy
HP:0000716	Depression
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001265	Hyporeflexia
HP:0001272	Cerebellar atrophy
HP:0001284	Areflexia
HP:0001621	Weak voice
HP:0001638	Cardiomyopathy
HP:0002013	Vomiting
HP:0002015	Dysphagia
HP:0002018	Nausea
HP:0002059	Cerebral atrophy
HP:0002067	Bradykinesia
HP:0002345	Action tremor
HP:0002362	Shuffling gait
HP:0002396	Cogwheel rigidity
HP:0002500	Abnormal cerebral white matter morphology
HP:0002505	Loss of ambulation
HP:0002548	Parkinsonism with favorable response to dopaminergic medication

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST004621_20	Red cell distribution width	3.000000e-14
GCST005993_50	Mean corpuscular hemoglobin	5.000000e-09
GCST006804_134	Red cell distribution width	3.000000e-10
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55
GCST90002390_502	Mean corpuscular hemoglobin	6.000000e-34
GCST90002392_555	Mean corpuscular volume	2.000000e-39
GCST90002396_452	Mean reticulocyte volume	2.000000e-27
GCST90002397_558	Mean spheric corpuscular volume	2.000000e-24
GCST90002397_559	Mean spheric corpuscular volume	1.000000e-12
GCST90002404_504	Red cell distribution width	6.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1830 (SINGLE PROTEIN), CHEMBL2095215 (PROTEIN COMPLEX GROUP), CHEMBL3301398 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 4,524 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL231616	TRIAPINE	3	4,524

Clinical evidence (CIViC)

Drug × variant × indication: 9 predictive associations from 11 curated evidence items; also 1 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
RRM1 Underexpression	Gemcitabine + Cisplatin	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID2905 +1
RRM1 Underexpression	Gemcitabine	Pancreatic Cancer	Sensitivity/Response	CIViC B	EID5506 +1
RRM1 Underexpression	Carboplatin + Gemcitabine	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID10143
RRM1 Underexpression	Paclitaxel + Gemcitabine + Cisplatin	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID12044
RRM1 Underexpression	Gemcitabine	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID5530
RRM1 Underexpression	Paclitaxel + Vinorelbine + Gemcitabine	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID5599
RRM1 Underexpression	Platinum Compound + Gemcitabine	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID6434
RRM1 Underexpression	Cisplatin + Gemcitabine	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID6436
RRM1 Overexpression	Gemcitabine	Pancreatic Cancer	Resistance	CIViC D	EID1859

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

13 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1042858	Efficacy	4	gemcitabine	Breast Neoplasms
rs1042919	Efficacy	3	cladribine;cytarabine	Leukemia;Myeloid;Acute
rs1042927	Efficacy	3	gemcitabine;Platinum compounds	Mesothelioma
rs11030918	Toxicity	3	gemcitabine;Platinum compounds	Mesothelioma
rs12806698	Toxicity	3	gemcitabine;Platinum compounds	Mesothelioma
rs12806698	Efficacy	3	gemcitabine;Platinum compounds	Non-Small Cell Lung Carcinoma
rs1561876	Efficacy	3	cladribine;cytarabine	Leukemia;Myeloid;Acute
rs183484	Efficacy	3	gemcitabine	Neoplasms
rs2284449	Efficacy	3	cisplatin;gemcitabine	Non-Small Cell Lung Carcinoma
rs232043	Efficacy	3	cisplatin;gemcitabine	Non-Small Cell Lung Carcinoma
rs2898950	Efficacy	3	cladribine;cytarabine	Leukemia;Myeloid;Acute
rs720106	Efficacy	3	cisplatin;gemcitabine	Non-Small Cell Lung Carcinoma
rs9937	Efficacy,Toxicity	3	gemcitabine	Neoplasms

PharmGKB variants

16 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9937	RRM1	3	5.75	1	gemcitabine
rs183484	RRM1	3	0.50	1	gemcitabine
rs232043	RRM1	3	3.00	1	cisplatin;gemcitabine
rs720106	RRM1	3	3.00	1	cisplatin;gemcitabine
rs725518	RRM1		0.00	0
rs1042858	RRM1	4	-0.50	1	gemcitabine
rs1042919	RRM1	3	2.25	1	cladribine;cytarabine
rs1042927	RRM1	3	1.25	1	gemcitabine;Platinum compounds
rs1561876	RRM1, STIM1	3	2.75	1	cladribine;cytarabine
rs2284449	RRM1	3	3.00	1	cisplatin;gemcitabine
rs2898950	RRM1, STIM1	3	1.75	1	cladribine;cytarabine
rs3817657	RRM1		0.00	0
rs7940013	RRM1		0.00	0
rs11030918	RRM1, STIM1	3	3.00	1	gemcitabine;Platinum compounds
rs12806698	RRM1, STIM1	3	3.00	2	gemcitabine;Platinum compounds
rs1735053	RRM1		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 1.17.4.1 Ribonucleoside-diphosphate reductases

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
clofarabine	Inhibition	8.3	pIC50
TAS1553	Binding	7.46	pKd
fludarabine	Inhibition	6.0	pIC50
hydroxyurea	Inhibition	3.83	pIC50

Binding affinities (BindingDB)

15 measured of 15 human assays (15 total across all organisms); most potent 15 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(4S)-5-chloro-N-[(1S,2R)-2-(6-fluoro-2,3-dimethylphenyl)-1-(2-oxo-3H-1,3,4-oxadiazol-5-yl)propyl]-4-hydroxy-4-(trideuteriomethyl)-2,3-dihydrochromene-8-sulfonamide	IC50	30 nM	US-12344588: Sulfonamide compounds and use thereof
5-chloro-N-[(1S,2R)-2-(6-fluoro-2,3-dimethylphenyl)-1-(2-oxo-3H-1,3,4-oxadiazol-5-yl)propyl]-4-hydroxy-4-(trideuteriomethyl)-2,3-dihydrochromene-8-sulfonamide	IC50	30 nM	US-20250223270: Sulfonamide Compounds and Use Thereof
dimethylphenyl)-1-(5-oxo-4,5-dihydro-	IC50	70 nM	US-20250223270: Sulfonamide Compounds and Use Thereof
(4R)-5-chloro-N-[(1S,2R)-2-(6-fluoro-2,3-dimethylphenyl)-1-(2-oxo-3H-1,3,4-oxadiazol-5-yl)propyl]-4-hydroxy-4-(trideuteriomethyl)-2,3-dihydrochromene-8-sulfonamide	IC50	80 nM	US-12344588: Sulfonamide compounds and use thereof
(4S)-5-chloro-N-[(1S,2R)-2-(3-chloro-6-fluoro-2-methylphenyl)-1-(2-oxo-3H-1,3,4-oxadiazol-5-yl)propyl]-4-hydroxy-4-(trideuteriomethyl)-2,3-dihydrochromene-8-sulfonamide	IC50	80 nM	US-12344588: Sulfonamide compounds and use thereof
5-chloro-N-[(1S,2R)-2-(6-fluoro-2,3-dimethylphenyl)-1-(2-oxo-3H-1,3,4-oxadiazol-5-yl)propyl]-4-hydroxy-4-(trideuteriomethyl)-2,3-dihydrochromene-8-sulfonamide	IC50	80 nM	US-20250223270: Sulfonamide Compounds and Use Thereof
5-chloro-N-((1S,2R)-2-(3-chloro-6-	IC50	80 nM	US-20250223270: Sulfonamide Compounds and Use Thereof
5-chloro-N-((1S,2R)-2-(6-fluoro-2,3-	IC50	80 nM	US-20250223270: Sulfonamide Compounds and Use Thereof
(4R)-5-chloro-N-[(1S,2R)-2-(3-chloro-6-fluoro-2-methylphenyl)-1-(2-oxo-3H-1,3,4-oxadiazol-5-yl)propyl]-4-hydroxy-4-(trideuteriomethyl)-2,3-dihydrochromene-8-sulfonamide	IC50	140 nM	US-12344588: Sulfonamide compounds and use thereof
fluoro-2-methylphenyl)-1-(5-oxo-4,5-	IC50	140 nM	US-20250223270: Sulfonamide Compounds and Use Thereof
Triapine	IC50	1200 nM	US-10155732: Ribonucleotide reductase inhibitors and methods of use
N-[4-(3,4-dihydroxyphenyl)-1,3-thiazol-2-yl]-3,4-dihydroxybenzamide	IC50	9300 nM	US-10155732: Ribonucleotide reductase inhibitors and methods of use
N-[4-(3,4-dihydroxyphenyl)-1,3-thiazol-2-yl]benzamide	IC50	15300 nM	US-10155732: Ribonucleotide reductase inhibitors and methods of use
3-[(E)-[4-(3,4-dihydroxyphenyl)-1,3-thiazol-2-yl]iminomethyl]-4-hydroxychromen-2-one	IC50	19100 nM	US-10155732: Ribonucleotide reductase inhibitors and methods of use
Hydroxyurea	IC50	148000 nM	US-10155732: Ribonucleotide reductase inhibitors and methods of use

ChEMBL bioactivities

374 potent at pChembl≥5 of 449 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.22	IC50	0.6	nM	CHEMBL336289
9.15	IC50	0.7	nM	CHEMBL96993
9.00	IC50	1	nM	CHEMBL98729
8.70	IC50	2	nM	CHEMBL1169533
8.52	IC50	3	nM	CHEMBL133754
8.52	IC50	3	nM	CHEMBL305199
8.40	IC50	4	nM	CHEMBL95998
8.30	IC50	5	nM	CHEMBL95766
8.30	IC50	5	nM	CHEMBL335164
8.22	IC50	6	nM	CHEMBL134961
8.19	IC50	6.4	nM	CHEMBL120710
8.15	IC50	7	nM	CHEMBL133827
8.15	IC50	7	nM	CHEMBL37210
8.12	IC50	7.5	nM	CHEMBL431851
7.82	IC50	15	nM	CHEMBL71945
7.75	IC50	18	nM	CHEMBL443029
7.70	IC50	20	nM	CHEMBL6001460
7.70	IC50	20	nM	CHEMBL1169532
7.66	IC50	22	nM	CHEMBL96993
7.66	IC50	22	nM	CHEMBL439791
7.66	IC50	22	nM	CHEMBL120060
7.62	IC50	24	nM	CHEMBL305229
7.57	IC50	27	nM	CHEMBL131682
7.52	IC50	30	nM	CHEMBL5941178
7.52	IC50	30	nM	CHEMBL5913113
7.47	IC50	34	nM	CHEMBL414818
7.44	IC50	36	nM	CHEMBL118524
7.43	IC50	37	nM	CHEMBL98729
7.40	IC50	40	nM	CHEMBL5958580
7.40	IC50	40	nM	CHEMBL5777432
7.40	IC50	40	nM	CHEMBL132130
7.37	IC50	43	nM	CHEMBL99950
7.30	IC50	50	nM	CHEMBL5813221
7.30	IC50	50	nM	CHEMBL5797621
7.30	IC50	50	nM	CHEMBL6028518
7.30	IC50	50	nM	CHEMBL5987707
7.26	IC50	55	nM	CHEMBL1169533
7.22	IC50	60	nM	CHEMBL5775741
7.22	IC50	60	nM	CHEMBL5869217
7.22	IC50	60	nM	CHEMBL5844268
7.22	IC50	60	nM	CHEMBL5793033
7.22	IC50	60	nM	CHEMBL5960405
7.22	IC50	60	nM	CHEMBL5824595
7.22	IC50	60	nM	CHEMBL5935086
7.22	IC50	60	nM	CHEMBL6057994
7.22	IC50	60	nM	CHEMBL5813221
7.22	IC50	60	nM	CHEMBL5988394
7.22	IC50	60	nM	CHEMBL6019064
7.22	IC50	60	nM	CHEMBL6058380
7.22	IC50	60	nM	CHEMBL5857144

PubChem BioAssay actives

79 with measured affinity, of 546 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4,4-dimethylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0006	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzyl-3-phenylpropanoyl)amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0007	uM
1-[(1S)-2-[[(1S)-1-carboxy-3-methylbutyl]amino]-1-[[(2S)-2-[[(2S)-3-methyl-2-[[(2S)-3-methyl-2-(3-phenylpropanoylamino)butanoyl]amino]butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-2-oxoethyl]cyclopentane-1-carboxylic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0010	uM
(2R)-2-[[(2R)-3-carboxy-2-[[(2S)-2-[[(2R)-2-[[(2R,6S)-2,6-dimethylcyclohexyl]carbamoylamino]-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0020	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0030	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-5,5-dimethyl-4-oxohexanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0030	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3,3-dimethyl-2-[[(2S)-3-methyl-2-(3-phenylpropanoylamino)butanoyl]amino]butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0040	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3-methyl-2-[[(2S)-3-methyl-2-(3-phenylpropanoylamino)butanoyl]amino]butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4,4-dimethylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0050	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2R,5S)-2-(3,3-dimethyl-2-oxobutyl)-6,6-dimethyl-4-oxo-5-(pentan-3-ylcarbamoylamino)heptanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0050	uM
(3S)-3-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-4-[[(2S)-1-hydroxy-4,4-dimethylpentan-2-yl]amino]-4-oxobutanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0060	uM
1-[(1S)-2-[[(1S)-1-carboxy-3-methylbutyl]amino]-1-[[(2S)-2-[[(2S)-2-(2-ethylbutanoylamino)-3,3-dimethylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-2-oxoethyl]cyclopent-3-ene-1-carboxylic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0064	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-2-(heptan-4-ylcarbamoylamino)-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0070	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S,5S)-6,6-dimethyl-4-oxo-2-(2-oxo-2-pyrrolidin-1-ylethyl)-5-(pentan-3-ylcarbamoylamino)heptanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0070	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3-methyl-2-[[(2S)-3-methyl-2-[methyl(3-phenylpropanoyl)amino]butanoyl]amino]butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0075	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3-methyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0150	uM
(3S)-4-[[(3R)-2,2-dimethylpentan-3-yl]amino]-3-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-4-oxobutanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0180	uM
(2R)-2-[[(2R)-3-carboxy-2-[[(2S)-2-[[(2R)-2-[[(2S,6S)-2,6-dimethylcyclohexyl]carbamoylamino]-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid;(2R)-2-[[(2R)-3-carboxy-2-[[(2S)-2-[[(2R)-2-[[(2R,6R)-2,6-dimethylcyclohexyl]carbamoylamino]-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0200	uM
(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[(2-benzyl-3-phenylpropanoyl)-methylamino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0220	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-cyclohexyl-2-(3-phenylpropanoylamino)acetyl]amino]-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0220	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3-methyl-2-[[(2S)-3-methyl-2-(3-phenylpropanoylamino)butanoyl]amino]butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0240	uM
(3S)-4-[[(2R)-3,3-dimethylbutan-2-yl]amino]-3-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-4-oxobutanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0270	uM
(3S)-4-[[(2S)-1-hydroxy-4,4-dimethylpentan-2-yl]amino]-3-[[(2S)-2-[[(2S)-3-methyl-2-[[(2S)-3-methyl-2-(3-phenylpropanoylamino)butanoyl]amino]butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-4-oxobutanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0340	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(3-phenylpropanoylamino)butanoyl]amino]-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0360	uM
(3S)-3-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-4-(2,2-dimethylpropylamino)-4-oxobutanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.0400	uM
(3S)-4-[[(1S)-1-carboxy-3-methylbutyl]amino]-3-[[(2S)-2-[[(2S)-2-(2-ethylbutanoylamino)-3,3-dimethylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-2,2-dimethyl-4-oxobutanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0430	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3-methyl-2-[[(2S,3S)-3-methyl-2-(3-phenylpropanoylamino)pentanoyl]amino]butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.0610	uM
(3S)-4-(3,3-dimethylbutylamino)-3-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-4-oxobutanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.1000	uM
(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[(2-benzyl-3-phenylpropanoyl)amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.1800	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3-methyl-2-[[(2S)-2-(3-phenylpropanoylamino)butanoyl]amino]butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.3400	uM
(3S)-3-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-4-(3-methylbutylamino)-4-oxobutanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.3500	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-3-methyl-2-(propan-2-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.4400	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-2-(cyclohexylcarbamoylamino)-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.5000	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-2-(2-ethylbutanoylamino)-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	0.8600	uM
(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-3-methyl-2-[[(2S)-3-methyl-2-[[(2R)-2-methyl-3-phenylpropanoyl]amino]butanoyl]amino]butanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.8600	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoic acid	198112: In vitro inhibitory activity against HSV ribonucleotide reductase	ic50	0.8800	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-(4-nitrophenyl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-4-amino-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoic acid	197834: Inhibitory concentration against HSV-1 ribonucleotide reductase R1 protein binding	ic50	1.5000	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149321: Binding affinity to human RRM1 incubated for 45 mins by Kinobead based pull down assay	kd	1.6693	uM
(3S)-3-[[(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[2-[9H-fluoren-9-ylmethoxycarbonyl(methyl)amino]-2-phenylacetyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-cyclohexylpropanoyl]amino]-4-[[(1S)-1-carboxy-2-phenylethyl]amino]-4-oxobutanoic acid	242343: Inhibition of mammalian ribonucleotide reductase in a standard dTTP-dependent GDP reductase assay	ic50	1.9000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-2-[[(2S)-2-acetamido-3-(1H-indol-3-yl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-4-amino-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoic acid	197834: Inhibitory concentration against HSV-1 ribonucleotide reductase R1 protein binding	ic50	1.9000	uM
(3S)-3-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-4-(2-methylpropylamino)-4-oxobutanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	1.9000	uM
(3S)-4-[[(3S)-2,2-dimethylpentan-3-yl]amino]-3-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-4-oxobutanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	2.0000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-4-amino-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoic acid	198110: Inhibitory concentration against HSV-1 ribonucleotide reductase R1 protein binding	ic50	2.2000	uM
(4S)-5-[[(2S)-1-[[(2S)-3-carboxy-1-[[(1S)-1-carboxy-2-phenylethyl]amino]-1-oxopropan-2-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[3-(9H-fluoren-9-ylmethoxy)-3-oxo-2-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-5-oxopentanoic acid	242343: Inhibition of mammalian ribonucleotide reductase in a standard dTTP-dependent GDP reductase assay	ic50	2.4000	uM
(3S)-3-[[(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[3-(9H-fluoren-9-ylmethoxy)-3-oxo-2-phenylpropanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-cyclohexylpropanoyl]amino]-4-[[(1S)-1-carboxy-2-phenylethyl]amino]-4-oxobutanoic acid	242343: Inhibition of mammalian ribonucleotide reductase in a standard dTTP-dependent GDP reductase assay	ic50	2.4000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S,3S)-2-[[(2S,3R)-2-[[2-[[(2S)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-methylpentanoyl]amino]-3-methylpentanoyl]amino]-4-amino-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoic acid	198110: Inhibitory concentration against HSV-1 ribonucleotide reductase R1 protein binding	ic50	2.6000	uM
(3S)-4-[[(2S)-3,3-dimethylbutan-2-yl]amino]-3-[[(2S)-2-[[(2S)-3,3-dimethyl-2-(pentan-3-ylcarbamoylamino)butanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-4-oxobutanoic acid	197982: Inhibitory effect was evaluated on Herpes simplex virus (HSV) ribonucleotide reductase (RR) enzyme.	ic50	2.7000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-2-[[(2S)-2-acetamido-3-(4-hydroxy-3-iodophenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-4-amino-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoic acid	197834: Inhibitory concentration against HSV-1 ribonucleotide reductase R1 protein binding	ic50	2.8000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2R)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-3-sulfanylpropanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-4-amino-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoic acid	198110: Inhibitory concentration against HSV-1 ribonucleotide reductase R1 protein binding	ic50	3.1000	uM
1-[(1S)-1-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzyl-3-phenylpropanoyl)-methylamino]-3-methylbutanoyl]amino]-3,3-dimethylbutanoyl]amino]-4-oxo-4-pyrrolidin-1-ylbutanoyl]amino]-2-[[(2S)-1-hydroxy-4,4-dimethylpentan-2-yl]amino]-2-oxoethyl]cyclopentane-1-carboxylic acid	41530: Inhibitory activity against HSV-1 in baby hamster kidney cell	ec50	3.1000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-4-amino-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoic acid	198110: Inhibitory concentration against HSV-1 ribonucleotide reductase R1 protein binding	ic50	3.2000	uM

CTD chemical–gene interactions

95 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	4
Arsenic Trioxide	affects binding, decreases reaction, decreases expression, increases expression	4
Acetaminophen	increases expression, decreases expression	3
Cyclosporine	affects expression, decreases expression	3
sodium arsenite	decreases methylation, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment, increases expression	2
Resveratrol	affects cotreatment, increases expression	2
Gemcitabine	decreases response to substance, increases expression, affects response to substance	2
Benzo(a)pyrene	increases expression, increases methylation	2
Cisplatin	increases expression	2
Estradiol	increases expression	2
Hydrogen Peroxide	affects expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	decreases expression	2
tert-Butylhydroperoxide	affects expression, decreases expression	2
Vitamin K 3	affects expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases reaction, increases degradation, decreases expression	1
dicrotophos	decreases expression	1
bismuth tripotassium dicitrate	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
methylselenic acid	affects expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction, increases reaction	1
afimoxifene	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1

ChEMBL screening assays

83 unique, capped per target: 80 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3243357	Binding	Inhibition of RRM1 in human U2OS cells assessed as gammaH2AX induction after 2 hrs by FITC/propidium iodide-staining based flow cytometry in presence of SCH900776	The identification of novel 5’-amino gemcitabine analogs as potent RRM1 inhibitors. — Bioorg Med Chem
CHEMBL652605	Functional	Inhibitory activity against HSV-1 in baby hamster kidney cell	Peptidomimetic inhibitors of herpes simplex virus ribonucleotide reductase: a new class of antiviral agents. — J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.