GMPS

Summary

GMPS (guanosine monophosphate synthase, HGNC:4378) is a protein-coding gene on chromosome 3q25.31, encoding GMP synthase [glutamine-hydrolyzing] (P49915). Catalyzes the conversion of xanthine monophosphate (XMP) to GMP in the presence of glutamine and ATP through an adenyl-XMP intermediate. It is a selective cancer dependency (DepMap: 77.9% of cell lines).

In the de novo synthesis of purine nucleotides, IMP is the branch point metabolite at which point the pathway diverges to the synthesis of either guanine or adenine nucleotides. In the guanine nucleotide pathway, there are 2 enzymes involved in converting IMP to GMP, namely IMP dehydrogenase (IMPD1), which catalyzes the oxidation of IMP to XMP, and GMP synthetase, which catalyzes the amination of XMP to GMP.

Source: NCBI Gene 8833 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 87 total
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 77.9% of screened cell lines
• MANE Select transcript: NM_003875

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4378
Approved symbol	GMPS
Name	guanosine monophosphate synthase
Location	3q25.31
Locus type	gene with protein product
Status	Approved
Aliases	GATD7
Ensembl gene	ENSG00000163655
Ensembl biotype	protein_coding
OMIM	600358
Entrez	8833

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 12 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000295920, ENST00000476145, ENST00000496455, ENST00000852009, ENST00000852010, ENST00000852011, ENST00000852012, ENST00000928984, ENST00000928985, ENST00000967990, ENST00000967991, ENST00000967992, ENST00000967993

RefSeq mRNA: 1 — MANE Select: NM_003875 NM_003875

CCDS: CCDS46941

Canonical transcript exons

ENST00000496455 — 16 exons

Exon	Start	End
ENSE00000779864	155916019	155916192
ENSE00000779865	155919233	155919338
ENSE00000779866	155922187	155922302
ENSE00000779870	155936338	155936510
ENSE00000805497	155931765	155931880
ENSE00000805498	155934916	155935046
ENSE00001169625	155925241	155925366
ENSE00001169644	155914419	155914570
ENSE00001169650	155911114	155911279
ENSE00001302106	155893518	155893699
ENSE00001315214	155910692	155910885
ENSE00001890402	155937591	155944020
ENSE00001951647	155870650	155870897
ENSE00003475173	155903863	155903960
ENSE00003539079	155897927	155898041
ENSE00003576441	155906160	155906263

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 96.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 64.0937 / max 362.1768, expressed in 1822 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39399	59.3672	1822
39398	3.5576	1438
39400	1.1689	582

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	96.85	gold quality
right testis	UBERON:0004534	96.74	gold quality
ventricular zone	UBERON:0003053	95.94	gold quality
ganglionic eminence	UBERON:0004023	95.17	gold quality
embryo	UBERON:0000922	95.16	gold quality
stromal cell of endometrium	CL:0002255	94.90	gold quality
testis	UBERON:0000473	94.58	gold quality
calcaneal tendon	UBERON:0003701	93.61	gold quality
islet of Langerhans	UBERON:0000006	92.82	gold quality
adrenal tissue	UBERON:0018303	92.61	gold quality
smooth muscle tissue	UBERON:0001135	92.03	gold quality
body of pancreas	UBERON:0001150	91.26	gold quality
colonic epithelium	UBERON:0000397	90.95	gold quality
pancreas	UBERON:0001264	90.95	gold quality
leukocyte	CL:0000738	90.76	gold quality
monocyte	CL:0000576	90.75	gold quality
rectum	UBERON:0001052	90.68	gold quality
cortical plate	UBERON:0005343	90.57	gold quality
bone marrow cell	CL:0002092	89.80	gold quality
vermiform appendix	UBERON:0001154	89.76	gold quality
skin of leg	UBERON:0001511	89.60	gold quality
tibial artery	UBERON:0007610	89.57	gold quality
popliteal artery	UBERON:0002250	89.56	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.47	gold quality
skin of abdomen	UBERON:0001416	89.33	gold quality
ectocervix	UBERON:0012249	89.28	gold quality
right adrenal gland cortex	UBERON:0035827	89.23	gold quality
left adrenal gland cortex	UBERON:0035825	89.08	gold quality
right adrenal gland	UBERON:0001233	89.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.05	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.74

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): APBB1, KAT5, TP53

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 77.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 7)

• analysis of USP7/HAUSP activation by its C-terminal ubiquitin-like domain and allosteric regulation by GMP-synthetase (PMID:21981925)
• Cytoplasmic sequestration of GMPS requires ubiquitylation by TRIM21. (PMID:24462112)
• Three genes-ATP6V1G1 in 9q32, GMPS in 3q25.31, and TBX5 in 12q24.21-exhibited concomitant hypermethylation and decreased expression. The i(12p)-positive cells displayed global hypomethylation of gene-poor regions on 12p, a footprint previously associated with constitutional and acquired gains of whole chromosomes as well as with X-chromosome inactivation in females (PMID:26890086)
• The GMPS SNP rs61750370 may be a reliable risk factor for extreme 6MMP preferential metabolism in patients with inflammatory bowel disease (PMID:29788244)
• Interactions of GMP with Human Glrx3 and with Saccharomyces cerevisiae Grx3 and Grx4 Converge in the Regulation of the Gcn2 Pathway. (PMID:32414791)
• Guanosine monophosphate synthase upregulation mediates cervical cancer progression by inhibiting the apoptosis of cervical cancer cells via the Stat3/P53 pathway. (PMID:33649833)
• The upregulated expression of RFC4 and GMPS mediated by DNA copy number alteration is associated with the early diagnosis and immune escape of ESCC based on a bioinformatic analysis. (PMID:34520390)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gmps	ENSDARG00000079848
mus_musculus	Gmps	ENSMUSG00000027823
rattus_norvegicus	Gmps	ENSRNOG00000051151
drosophila_melanogaster	bur	FBGN0000239
caenorhabditis_elegans		WBGENE00010912

Protein

Protein identifiers

GMP synthase [glutamine-hydrolyzing] — P49915 (reviewed: P49915)

Alternative names: GMP synthetase, Glutamine amidotransferase

All UniProt accessions (2): A0A140VJK6, P49915

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the conversion of xanthine monophosphate (XMP) to GMP in the presence of glutamine and ATP through an adenyl-XMP intermediate.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm. Cytosol.

Disease relevance. A chromosomal aberration involving GMPS is found in acute myeloid leukemias. Translocation t(3,11)(q25,q23) with KMT2A/MLL1.

Pathway. Purine metabolism; GMP biosynthesis; GMP from XMP (L-Gln route): step 1/1.

Isoforms (2)

UniProt ID	Names	Canonical?
P49915-1	1	yes
P49915-2	2

RefSeq proteins (1): NP_003866* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001674	GMP_synth_C	Domain
IPR004739	GMP_synth_GATase	Domain
IPR014729	Rossmann-like_a/b/a_fold	Homologous_superfamily
IPR017926	GATASE	Domain
IPR022310	NAD/GMP_synthase	Domain
IPR025777	GMPS_ATP_PPase_dom	Domain
IPR029062	Class_I_gatase-like	Homologous_superfamily

Pfam: PF00117, PF00958, PF02540

Enzyme classification (BRENDA):

• EC 6.3.5.2 — GMP synthase (glutamine-hydrolysing) (BRENDA: 23 organisms, 59 substrates, 115 inhibitors, 69 Km, 27 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
XMP	0.0036–0.166	23
ATP	0.027–0.53	14
L-GLUTAMINE	0.472–99	8
GLN	0.21–0.68	6
NH4+	1–36	5
NH3	0.09–0.132	4
8-AZAXMP	0.05–0.35	2
1-RIBOSYL-4,6-DIHYDROXYPYRAZOLO[3,4-D]-PYRIMIDIN	2	1
2-DXMP	0.125	1
6-THIOXMP	0.42	1
GMP	0.0112	1
L-GLN	0.472	1
MGATP2-	0.11	1

Catalyzed reactions (Rhea), 1 shown:

• XMP + L-glutamine + ATP + H2O = GMP + L-glutamate + AMP + diphosphate + 2 H(+) (RHEA:11680)

UniProt features (78 total): helix 29, strand 24, binding site 6, modified residue 5, turn 4, active site 3, sequence conflict 2, domain 2, initiator methionine 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2VPI	X-RAY DIFFRACTION	2.4
2VXO	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49915-F1	87.06	0.63

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 (3): 104 (for gatase activity); 190 (for gatase activity); 192 (for gatase activity)

Ligand- & substrate-binding residues (6): 610; 685; 691; 244–250; 337; 522

Post-translational modifications (5): 2, 8, 9, 318, 332

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-73817	Purine ribonucleoside monophosphate biosynthesis
R-HSA-9748787	Azathioprine ADME

MSigDB gene sets: 180 (showing top): GNF2_CKS1B, MODULE_52, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MODULE_56, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, MODULE_16, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, PUJANA_CHEK2_PCC_NETWORK, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, MODULE_118

GO Biological Process (4): GMP biosynthetic process (GO:0006177), purine nucleobase biosynthetic process (GO:0009113), purine ribonucleoside monophosphate biosynthetic process (GO:0009168), purine nucleotide biosynthetic process (GO:0006164)

GO Molecular Function (5): GMP synthase activity (GO:0003921), GMP synthase (glutamine-hydrolyzing) activity (GO:0003922), ATP binding (GO:0005524), nucleotide binding (GO:0000166), ligase activity (GO:0016874)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Nucleotide biosynthesis	1
Drug ADME	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
purine-containing compound biosynthetic process	2
cellular anatomical structure	2
purine ribonucleotide biosynthetic process	1
purine ribonucleoside monophosphate biosynthetic process	1
GMP metabolic process	1
purine nucleobase metabolic process	1
nucleobase biosynthetic process	1
purine nucleoside monophosphate biosynthetic process	1
ribonucleoside monophosphate biosynthetic process	1
purine ribonucleoside monophosphate metabolic process	1
purine nucleotide metabolic process	1
nucleotide biosynthetic process	1
GMP synthase (glutamine-hydrolyzing) activity	1
ligase activity, forming carbon-nitrogen bonds	1
GMP biosynthetic process	1
carbon-nitrogen ligase activity, with glutamine as amido-N-donor	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

4362 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GMPS	USP7	Q93009	987
GMPS	IMPDH1	P20839	922
GMPS	IMPDH2	P12268	877
GMPS	ATIC	P31939	818
GMPS	ADSL	P30566	792
GMPS	GART	P22102	785
GMPS	ADSS2	P30520	770
GMPS	PPAT	Q06203	759
GMPS	CTPS1	P17812	731
GMPS	APRT	P07741	718
GMPS	MTHFD2	P13995	706
GMPS	MTHFD1	P11586	705
GMPS	CTPS2	Q9NRF8	695
GMPS	UMPS	P11172	675
GMPS	AMPD2	Q01433	669

IntAct

93 interactions, top by confidence:

A	B	Type	Score
AKR7A3	AKR7A2	psi-mi:“MI:0914”(association)	0.890
CNOT3	CNOT1	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
GPX7	GAK	psi-mi:“MI:0914”(association)	0.640
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
PPM1G	COPE	psi-mi:“MI:0914”(association)	0.530
MPHOSPH6	ZFC3H1	psi-mi:“MI:0914”(association)	0.530
VGLL4	YAP1	psi-mi:“MI:0914”(association)	0.530
VCAM1	PSMD11	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
AGPAT2	GMPS	psi-mi:“MI:0915”(physical association)	0.370
ZNF16	GMPS	psi-mi:“MI:0915”(physical association)	0.370
		psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
Nedd1		psi-mi:“MI:0914”(association)	0.350
Racgap1	DDX3X	psi-mi:“MI:0914”(association)	0.350
Pkm	BRINP1	psi-mi:“MI:0914”(association)	0.350
AGO2	GMPS	psi-mi:“MI:0914”(association)	0.350
KIF7	TBC1D31	psi-mi:“MI:0914”(association)	0.350
PAX6	EPB41L2	psi-mi:“MI:0914”(association)	0.350
Wdr48	DMWD	psi-mi:“MI:0914”(association)	0.350
USP7	STIL	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
ANG	DDX39A	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350

BioGRID (223): CTPS1 (Co-fractionation), GLO1 (Co-fractionation), GMPS (Co-fractionation), GMPS (Co-fractionation), GMPS (Co-fractionation), IMPDH1 (Co-fractionation), IMPDH2 (Co-fractionation), USP7 (Co-fractionation), GMPS (Affinity Capture-MS), GMPS (Affinity Capture-MS), GMPS (Affinity Capture-MS), GMPS (Affinity Capture-MS), GMPS (Affinity Capture-MS), GMPS (Affinity Capture-MS), GMPS (Affinity Capture-MS)

ESM2 similar proteins: A0A075D5I4, A0A075D654, A0A075D657, A0A075D6M1, A0A1D6NER6, A0A482NB13, A0A8X8M4T9, A0A8X8M4W6, A0A8X8M501, A0A8X8M505, A4GNA8, A6ZRD1, C8YTM5, O74529, O94634, P32643, P34254, P49915, P50135, P52788, P97355, Q09580, Q10170, Q16KN5, Q22993, Q29LW1, Q3SZA5, Q3THK7, Q4V7C6, Q55DH6, Q5PP70, Q5R7C3, Q5RA96, Q6C3P4, Q6DC37, Q6DW73, Q83WC3, Q8IDQ9, Q8VYX1, Q93V78

Diamond homologs: A0AHK7, A0Q2S8, A0R8W7, A1W0N3, A2RED2, A4XKX8, A5I720, A5N5D9, A5VLY3, A6LQ90, A6TLR3, A7FYP0, A7GIN0, A7GKG1, A7Z235, A8FAH5, A9VQG9, B0S0S7, B0TI09, B1IFD1, B1L1J7, B1YIZ1, B2G994, B2TIX3, B2UZ05, B3ELI1, B3W952, B5XLN9, B7H4Q8, B7IUT1, B7JM61, B8D0Z5, B8I4P0, B9DYY7, B9KFL4, C0QYF1, C1EUB4, C1FLV2, C3KUC5, C3L508

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
GMPS	up-regulates	TP53	binding
TRIM21	down-regulates	GMPS	ubiquitination
GMPS	“down-regulates quantity”	“5’-xanthylic acid”	“chemical modification”
GMPS	“up-regulates quantity”	“guanosine 5’-monophosphate”	“chemical modification”
GMPS	“down-regulates quantity”	“L-glutamine zwitterion”	“chemical modification”
GMPS	“up-regulates quantity”	L-glutamate(1-)	“chemical modification”
TP53	“down-regulates quantity by repression”	GMPS	“transcriptional regulation”

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — HCC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	0
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

2857 predictions. Top by Δscore:

Variant	Effect	Δscore
3:155893506:T:TA	acceptor_gain	1.0000
3:155893510:A:AG	acceptor_gain	1.0000
3:155893511:T:G	acceptor_gain	1.0000
3:155893515:CAGC:C	acceptor_loss	1.0000
3:155893516:A:AG	acceptor_gain	1.0000
3:155893516:AGCT:A	acceptor_gain	1.0000
3:155893516:AGCTG:A	acceptor_gain	1.0000
3:155893517:G:GC	acceptor_gain	1.0000
3:155893517:GC:G	acceptor_gain	1.0000
3:155893517:GCT:G	acceptor_gain	1.0000
3:155893517:GCTG:G	acceptor_gain	1.0000
3:155893517:GCTGG:G	acceptor_gain	1.0000
3:155893598:G:GG	donor_gain	1.0000
3:155893605:A:T	donor_gain	1.0000
3:155893621:GA:G	donor_gain	1.0000
3:155893623:G:GG	donor_gain	1.0000
3:155893629:G:T	donor_gain	1.0000
3:155893686:G:GT	donor_gain	1.0000
3:155893687:A:T	donor_gain	1.0000
3:155893693:G:GT	donor_gain	1.0000
3:155897919:A:G	acceptor_gain	1.0000
3:155897925:A:AG	acceptor_gain	1.0000
3:155897926:G:GG	acceptor_gain	1.0000
3:155903856:T:TA	acceptor_gain	1.0000
3:155903861:A:AG	acceptor_gain	1.0000
3:155903861:A:T	acceptor_loss	1.0000
3:155903861:AGAT:A	acceptor_gain	1.0000
3:155903862:G:A	acceptor_loss	1.0000
3:155903862:G:GA	acceptor_gain	1.0000
3:155903862:GAT:G	acceptor_gain	1.0000

AlphaMissense

4553 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:155893618:G:C	R43P	1.000
3:155898022:G:A	G102E	1.000
3:155898027:T:C	C104R	1.000
3:155898029:C:G	C104W	1.000
3:155898034:G:A	G106D	1.000
3:155910733:C:G	H190D	1.000
3:155911123:A:C	S244R	1.000
3:155911125:T:A	S244R	1.000
3:155911125:T:G	S244R	1.000
3:155911127:G:A	G245D	1.000
3:155911136:A:T	D248V	1.000
3:155911138:T:C	S249P	1.000
3:155911220:G:C	R276T	1.000
3:155911220:G:T	R276I	1.000
3:155911221:A:C	R276S	1.000
3:155911221:A:T	R276S	1.000
3:155914439:T:C	F303L	1.000
3:155914441:C:A	F303L	1.000
3:155914441:C:G	F303L	1.000
3:155914540:A:C	K336N	1.000
3:155914540:A:T	K336N	1.000
3:155914542:G:C	R337T	1.000
3:155914543:A:C	R337S	1.000
3:155914543:A:T	R337S	1.000
3:155914553:G:A	G341R	1.000
3:155914553:G:C	G341R	1.000
3:155914553:G:T	G341W	1.000
3:155914554:G:A	G341E	1.000
3:155914562:T:C	F344L	1.000
3:155914564:T:A	F344L	1.000

dbSNP variants (sampled 300 via entrez): RS1000007607 (3:155905090 C>A,T), RS1000225992 (3:155930969 C>T), RS1000253567 (3:155878690 T>C), RS1000296175 (3:155927732 T>C), RS1000340093 (3:155937311 G>T), RS1000414875 (3:155884598 A>T), RS1000420144 (3:155895210 T>C), RS1000427471 (3:155930715 C>A,G,T), RS1000500655 (3:155897597 C>G,T), RS1000515689 (3:155879482 G>A), RS1000560241 (3:155932458 C>T), RS1000576255 (3:155929031 T>C), RS1000586235 (3:155879870 T>A), RS1000586884 (3:155934553 C>G), RS1000628737 (3:155929293 A>G)

Disease associations

OMIM: gene MIM:600358 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009018_1	Blood metabolite levels	9.000000e-10
GCST010573_2	Cardiorespiratory fitness (800m run time)	9.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004328	exercise test

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5721 (SINGLE PROTEIN)

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs61750368	GMPS		0.00	0
rs4679758	GMPS		0.00	0

Binding affinities (BindingDB)

3 measured of 5 human assays (5 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-chloro-N-[4-(3-prop-2-ynoxyanilino)quinazolin-6-yl]acetamide	IC50	6.2 nM	US-20250263383: NOVEL INHIBITORS OF GUANOSINE MONOPHOSPHATE SYNTHETASE AS THERAPEUTIC AGENTS
2-chloro-N-[4-(3-methoxyanilino)quinazolin-6-yl]acetamide	IC50	23 nM	US-20250263383: NOVEL INHIBITORS OF GUANOSINE MONOPHOSPHATE SYNTHETASE AS THERAPEUTIC AGENTS
3-[(2-chloroacetyl)amino]-N-(3-prop-2-ynoxyphenyl)benzamide	IC50	98 nM	US-20250263383: NOVEL INHIBITORS OF GUANOSINE MONOPHOSPHATE SYNTHETASE AS THERAPEUTIC AGENTS

ChEMBL bioactivities

5 potent at pChembl≥5 of 7 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.21	IC50	6.2	nM	CHEMBL5094230
7.64	IC50	23	nM	CHEMBL5093024
7.01	IC50	98	nM	CHEMBL5080411
6.76	Kd	173.1	nM	CHEMBL5653589
6.76	ED50	173.1	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 16 total; 1 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148440: Binding affinity to human GMPS incubated for 45 mins by Kinobead based pull down assay	kd	0.1731	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	decreases expression, increases expression, affects binding, decreases reaction	3
bisphenol A	decreases expression	2
Benzo(a)pyrene	affects methylation, affects cotreatment, increases expression	2
Valproic Acid	decreases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
poly(propyleneimine)	decreases expression	1
oligofectamine	increases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
bromovanin	decreases expression	1
bisphenol S	increases expression	1
NSC 689534	affects binding, decreases expression	1
bisphenol AF	increases expression	1
Air Pollutants, Occupational	affects expression	1
Atrazine	increases expression	1
Caffeine	increases phosphorylation	1
Cisplatin	decreases response to substance, increases expression	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1032551	Binding	Inhibition of GMPS in human A3.01 cells at 50 uM	Enzyme inhibitors: new and known polybrominated phenols and diphenyl ethers from four Indo-Pacific Dysidea sponges. — J Nat Prod

Clinical trials (associated diseases)

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