CTPS2

Summary

CTPS2 (CTP synthase 2, HGNC:2520) is a protein-coding gene on chromosome Xp22.2, encoding CTP synthase 2 (Q9NRF8). CTP synthase involved in the de novo synthesis of CTP, a precursor of DNA, RNA and phospholipids.

The protein encoded by this gene catalyzes the formation of CTP from UTP with the concomitant deamination of glutamine to glutamate. This protein is the rate-limiting enzyme in the synthesis of cytosine nucleotides, which play an important role in various metabolic processes and provide the precursors necessary for the synthesis of RNA and DNA. Cancer cells that exhibit increased cell proliferation also exhibit an increased activity of this encoded protein. Thus, this protein is an attractive target for selective chemotherapy. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 56474 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 201 total
• Druggable target: yes
• MANE Select transcript: NM_175859

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2520
Approved symbol	CTPS2
Name	CTP synthase 2
Location	Xp22.2
Locus type	gene with protein product
Status	Approved
Aliases	GATD5B
Ensembl gene	ENSG00000047230
Ensembl biotype	protein_coding
OMIM	300380
Entrez	56474

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 36 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000359276, ENST00000380241, ENST00000443824, ENST00000455276, ENST00000483053, ENST00000870414, ENST00000870415, ENST00000870416, ENST00000870417, ENST00000870418, ENST00000870419, ENST00000870420, ENST00000870421, ENST00000870422, ENST00000870423, ENST00000870424, ENST00000870425, ENST00000870426, ENST00000870427, ENST00000870428, ENST00000913871, ENST00000913872, ENST00000913873, ENST00000913874, ENST00000913875, ENST00000913876, ENST00000944979, ENST00000944980, ENST00000944981, ENST00000944982, ENST00000944983, ENST00000944984, ENST00000944985, ENST00000944986, ENST00000944987, ENST00000944988, ENST00000944989

RefSeq mRNA: 3 — MANE Select: NM_175859 NM_001144002, NM_019857, NM_175859

CCDS: CCDS14175

Canonical transcript exons

ENST00000359276 — 19 exons

Exon	Start	End
ENSE00001150642	16639147	16639243
ENSE00001150648	16667514	16667557
ENSE00001150654	16667662	16667724
ENSE00001150661	16670580	16670674
ENSE00001150669	16678362	16678450
ENSE00001201944	16609541	16609685
ENSE00001201948	16617150	16617246
ENSE00001201953	16620277	16620332
ENSE00001277888	16590752	16590862
ENSE00001430890	16712335	16712669
ENSE00001612556	16693371	16693487
ENSE00001622171	16691540	16691620
ENSE00001708554	16698923	16699093
ENSE00001710627	16689450	16689601
ENSE00001723130	16698236	16698336
ENSE00001733932	16693141	16693224
ENSE00001778300	16683094	16683226
ENSE00002731939	16702737	16702941
ENSE00003843996	16587999	16589775

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 90.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.9775 / max 137.5056, expressed in 1689 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198564	6.0931	1602
198565	3.2848	1148
198566	0.3811	208
198567	0.2185	114

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	90.02	gold quality
ventricular zone	UBERON:0003053	89.92	gold quality
body of pancreas	UBERON:0001150	88.60	gold quality
endocervix	UBERON:0000458	87.93	gold quality
right ovary	UBERON:0002118	87.89	gold quality
left ovary	UBERON:0002119	87.85	gold quality
ganglionic eminence	UBERON:0004023	87.69	gold quality
calcaneal tendon	UBERON:0003701	87.46	gold quality
duodenum	UBERON:0002114	86.81	gold quality
adrenal tissue	UBERON:0018303	86.73	gold quality
ovary	UBERON:0000992	86.69	gold quality
right uterine tube	UBERON:0001302	85.92	gold quality
visceral pleura	UBERON:0002401	85.83	gold quality
endometrium	UBERON:0001295	85.63	gold quality
ectocervix	UBERON:0012249	85.61	gold quality
body of uterus	UBERON:0009853	85.30	gold quality
minor salivary gland	UBERON:0001830	85.27	gold quality
right adrenal gland cortex	UBERON:0035827	85.20	gold quality
pancreas	UBERON:0001264	85.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.76	gold quality
body of stomach	UBERON:0001161	84.61	gold quality
rectum	UBERON:0001052	84.55	gold quality
right adrenal gland	UBERON:0001233	84.55	gold quality
embryo	UBERON:0000922	84.46	gold quality
tibial nerve	UBERON:0001323	84.42	gold quality
pleura	UBERON:0000977	84.27	gold quality
parietal pleura	UBERON:0002400	84.19	gold quality
mucosa of stomach	UBERON:0001199	84.18	gold quality
right lobe of liver	UBERON:0001114	84.06	gold quality
skin of abdomen	UBERON:0001416	84.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

88 targeting CTPS2, 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-4425	100.00	67.59	1049
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-485-3P	99.98	70.68	1585
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-944	99.82	70.85	3042

Literature-anchored findings (GeneRIF, showing 4)

• analysis of the kinetic properties of hCTPS1 and hCTPS2, and determination that Ser(68) is a major site of CTPS2 regulation by phosphorylation (PMID:20739275)
• CTPS2 was identified by genome-wide gene expression analyses as correlated with cellular sensitivity to cisplatin and carboplatin. (PMID:21252287)
• Low CTPS2 expression may be a rationally-based determinant of 5FU resistance. (PMID:21378502)
• Cryo-EM structures reveal that CTPS2 filaments dynamically switch between active and inactive forms in response to changes in substrate and product levels. (PMID:31873303)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ctps2	ENSMUSG00000031360
rattus_norvegicus	Ctps2	ENSRNOG00000004257
drosophila_melanogaster	Ctps	FBGN0266452
caenorhabditis_elegans		WBGENE00012316

Paralogs (1): CTPS1 (ENSG00000171793)

Protein

Protein identifiers

CTP synthase 2 — Q9NRF8 (reviewed: Q9NRF8)

Alternative names: CTP synthetase 2, UTP–ammonia ligase 2

All UniProt accessions (2): Q9NRF8, H0Y5S6

UniProt curated annotations — full annotation on UniProt →

Function. CTP synthase involved in the de novo synthesis of CTP, a precursor of DNA, RNA and phospholipids. Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as a source of nitrogen. Constitutes the rate-limiting enzyme in the synthesis of cytosine nucleotides.

Subunit / interactions. Homotetramer. Polymerizes into filaments of stacked tetramers through conserved intertetramer interactions. Filaments dynamically switch between substrate- (active) and product-bound (inactive) conformations with unique architectures.

Subcellular location. Cytoplasm. Cytosol. Nucleus.

Activity regulation. Strongly inhibited by CTP.

Pathway. Pyrimidine metabolism; CTP biosynthesis via de novo pathway; CTP from UDP: step 2/2.

Similarity. Belongs to the CTP synthase family.

RefSeq proteins (3): NP_001137474, NP_062831, NP_787055* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004468	CTP_synthase	Family
IPR017456	CTP_synthase_N	Domain
IPR017926	GATASE	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR029062	Class_I_gatase-like	Homologous_superfamily
IPR033828	GATase1_CTP_Synthase	Domain

Pfam: PF00117, PF06418

Enzyme classification (BRENDA):

• EC 6.3.4.2 — CTP synthase (glutamine hydrolysing) (BRENDA: 19 organisms, 51 substrates, 113 inhibitors, 75 Km, 92 kcat entries)

Substrate kinetics (BRENDA)

19 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
UTP	0.027–12.4	16
L-GLUTAMINE	0.1–39.4	9
NH3	0.627–2.79	7
NH4+	54–92	6
NH4CL	0.7–4.1	6
NH4OAC	0.94–4.2	6
ATP	0.002–0.54	5
GLUTAMINE	0.196–0.424	4
GLN	0.259–0.497	3
L-GLN	0.027–0.1	3
GLN-OH	0.063–0.165	2
NH2OH	75.3–82.8	2
GTP	0.07	1
2’,3’-DIALDEHYDE ADENOSINE 5’-TRIPHOSPHATE	—	0
2’-DEOXY-GTP	—	0

Catalyzed reactions (Rhea), 1 shown:

• UTP + L-glutamine + ATP + H2O = CTP + L-glutamate + ADP + phosphate + 2 H(+) (RHEA:26426)

UniProt features (115 total): binding site 40, helix 29, strand 28, turn 4, active site 3, modified residue 3, sequence conflict 3, mutagenesis site 2, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
2V4U	X-RAY DIFFRACTION	2.3
2VKT	X-RAY DIFFRACTION	2.5
7MII	ELECTRON MICROSCOPY	2.7
3IHL	X-RAY DIFFRACTION	2.8
7MH1	ELECTRON MICROSCOPY	2.8
7MIH	ELECTRON MICROSCOPY	2.8
6PK7	ELECTRON MICROSCOPY	3.1
6PK4	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRF8-F1	91.79	0.84

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): 399 (for gatase activity); 526 (for gatase activity); 528 (for gatase activity)

Ligand- & substrate-binding residues (40): 15; 15; 16; 16; 18; 21; 21; 38; 40; 55; 70; 70 …

Post-translational modifications (3): 568, 571, 574

Mutagenesis-validated functional residues (2):

Position	Phenotype
250	promotes inhibition by small compound r80.
355	abolished ability to polymerize into filaments.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 151 (showing top): PAL_PRMT5_TARGETS_UP, GOBP_PYRIMIDINE_NUCLEOSIDE_TRIPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PYRIMIDINE_NUCLEOBASE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_PYRIMIDINE_NUCLEOTIDE_METABOLIC_PROCESS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, GOBP_NUCLEOBASE_METABOLIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOSIDE_TRIPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_TRIPHOSPHATE_BIOSYNTHETIC_PROCESS

GO Biological Process (6): pyrimidine nucleotide metabolic process (GO:0006220), CTP biosynthetic process (GO:0006241), pyrimidine nucleobase biosynthetic process (GO:0019856), ‘de novo’ CTP biosynthetic process (GO:0044210), pyrimidine nucleotide biosynthetic process (GO:0006221), small molecule metabolic process (GO:0044281)

GO Molecular Function (6): CTP synthase activity (GO:0003883), ATP binding (GO:0005524), identical protein binding (GO:0042802), nucleotide binding (GO:0000166), protein binding (GO:0005515), ligase activity (GO:0016874)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), cytoophidium (GO:0097268)

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
pyrimidine-containing compound biosynthetic process	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
cytoplasm	2
nucleotide metabolic process	1
pyrimidine-containing compound metabolic process	1
pyrimidine ribonucleoside triphosphate biosynthetic process	1
pyrimidine ribonucleotide biosynthetic process	1
CTP metabolic process	1
pyrimidine nucleobase metabolic process	1
nucleobase biosynthetic process	1
CTP biosynthetic process	1
pyrimidine nucleotide metabolic process	1
nucleotide biosynthetic process	1
metabolic process	1
ligase activity, forming carbon-nitrogen bonds	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
supramolecular fiber	1

Protein interactions and networks

STRING

3166 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTPS2	GMPS	P49915	695
CTPS2	UMPS	P11172	645
CTPS2	DHODH	Q02127	600
CTPS2	TYMS	P04818	583
CTPS2	PPAT	Q06203	566
CTPS2	IMPDH2	P12268	541
CTPS2	DCTD	P32321	535
CTPS2	TCEANC	Q8N8B7	534
CTPS2	UCKL1	Q9NWZ5	512
CTPS2	CMPK1	P30085	511
CTPS2	UCK1	Q9HA47	500
CTPS2	UPRT	Q96BW1	491
CTPS2	CDA	P32320	491
CTPS2	ADSL	P30566	486
CTPS2	ASNS	P08184	484

IntAct

93 interactions, top by confidence:

A	B	Type	Score
CTPS2	CTPS1	psi-mi:“MI:0915”(physical association)	0.850
CTPS1	CTPS2	psi-mi:“MI:0915”(physical association)	0.850
CTPS2	CTPS1	psi-mi:“MI:0914”(association)	0.850
CTPS2	CTPS2	psi-mi:“MI:0915”(physical association)	0.790
CTPS2	CTPS2	psi-mi:“MI:0407”(direct interaction)	0.790
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CTPS2	SPG21	psi-mi:“MI:0915”(physical association)	0.670
SPG21	CTPS2	psi-mi:“MI:0915”(physical association)	0.670
RNASEH2C	RNASEH2A	psi-mi:“MI:0914”(association)	0.640
CTPS2		psi-mi:“MI:0915”(physical association)	0.560
	CTPS2	psi-mi:“MI:0915”(physical association)	0.560
PRSS22	PPM1A	psi-mi:“MI:0914”(association)	0.560
TIGD3	CTPS1	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
SPATA46	MDM4	psi-mi:“MI:0914”(association)	0.530
NPPA	VGF	psi-mi:“MI:0914”(association)	0.530

BioGRID (138): CTPS2 (Two-hybrid), CTPS2 (Two-hybrid), CTPS2 (Affinity Capture-MS), CTPS2 (Affinity Capture-MS), CTPS2 (Affinity Capture-MS), CTPS2 (Affinity Capture-MS), CTPS2 (Two-hybrid), CTPS2 (Two-hybrid), CTPS2 (Affinity Capture-MS), CTPS2 (Affinity Capture-MS), CTPS2 (Affinity Capture-MS), CTPS2 (Affinity Capture-MS), CTPS2 (Affinity Capture-MS), CTPS2 (Affinity Capture-MS), CTPS1 (Affinity Capture-MS)

ESM2 similar proteins: A0AVT1, A0JMS7, A2BP19, A6H630, B0C2K7, B3EK39, B3MF31, B4MNL1, B4P925, B4S3A5, P17812, P46446, P50547, P59830, P70698, P72208, Q10VR3, Q1LXS2, Q1RMS2, Q28C61, Q2NL24, Q3MC79, Q58EM4, Q5BJ91, Q5F3Z1, Q5M876, Q5RBT2, Q5XGC5, Q6AXB1, Q6AYT5, Q6DHI0, Q6DHQ3, Q6DJA3, Q7SYV1, Q7TS68, Q8C7R4, Q8R3P0, Q8YQC1, Q91XE4, Q969U7

Diamond homologs: A0B7H6, A0RLC3, A2SSJ7, A3DGR3, A6LQF6, A6UTE4, A6ZQ59, A7GV88, A7Z9T4, A8FIE5, A9VSD6, B0CBC7, B0R6G2, B4U6A9, B6YTF0, B7HFN6, B7HY98, B7IQZ1, B7JHG1, B8HNM9, B8I598, B9IRX1, C1F0R6, C3LFL2, C3P2A0, C5A7F1, G0HV10, O29987, O42644, O59456, O74638, P13242, P17812, P28274, P38627, P50547, P70303, P70698, Q0SQX5, Q0TNA4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CSNK1A1	down-regulates	CTPS2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

4174 predictions. Top by Δscore:

Variant	Effect	Δscore
X:16589777:T:C	acceptor_gain	1.0000
X:16617148:A:AC	donor_gain	1.0000
X:16617149:C:CC	donor_gain	1.0000
X:16617149:CTTG:C	donor_gain	1.0000
X:16620331:CC:C	acceptor_gain	1.0000
X:16620332:CC:C	acceptor_gain	1.0000
X:16651142:G:GG	donor_gain	1.0000
X:16652695:A:AG	acceptor_gain	1.0000
X:16678360:A:AC	donor_gain	1.0000
X:16678361:C:CA	donor_gain	1.0000
X:16678361:CT:C	donor_gain	1.0000
X:16678361:CTCA:C	donor_gain	1.0000
X:16678361:CTCAG:C	donor_gain	1.0000
X:16678365:G:C	donor_gain	1.0000
X:16678449:TA:T	acceptor_gain	1.0000
X:16678451:C:CC	acceptor_gain	1.0000
X:16683089:CTCA:C	donor_loss	1.0000
X:16683090:TCAC:T	donor_loss	1.0000
X:16683091:CA:C	donor_loss	1.0000
X:16683092:A:AC	donor_gain	1.0000
X:16683092:A:C	donor_loss	1.0000
X:16683092:AC:A	donor_gain	1.0000
X:16683092:ACCAT:A	donor_gain	1.0000
X:16683093:C:CC	donor_gain	1.0000
X:16683093:C:CG	donor_loss	1.0000
X:16683093:CC:C	donor_gain	1.0000
X:16683093:CCAT:C	donor_gain	1.0000
X:16683093:CCATC:C	donor_gain	1.0000
X:16683224:TAC:T	acceptor_gain	1.0000
X:16693357:T:C	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000013693 (X:16667988 C>T), RS1000067418 (X:16668572 G>A,C), RS1000083859 (X:16636940 TA>T), RS1000132252 (X:16625673 A>C), RS1000172125 (X:16637882 C>A,T), RS1000186008 (X:16646108 A>G), RS1000216293 (X:16589195 A>G), RS1000238498 (X:16649358 T>C), RS1000280321 (X:16660450 G>A), RS1000310737 (X:16675487 G>A), RS1000320144 (X:16671762 G>A), RS1000365891 (X:16693798 T>C), RS1000371904 (X:16684912 G>A), RS1000424322 (X:16685257 C>T), RS1000467667 (X:16614694 TGA>T)

Disease associations

OMIM: gene MIM:300380 | disease phenotypes: MIM:601086

GenCC curated gene-disease

Mondo (1): laterality defects, autosomal dominant (MONDO:0010991)

Orphanet (1): Visceral heterotaxy (Orphanet:450)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008772_6	Suicide	1.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007624	suicide

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563391	Laterality Defects, Autosomal Dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5291524 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Nucleotide turnover

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 27 [PMID: 36449304]	Inhibition	7.74	pIC50

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.75	IC50	18	nM	CHEMBL5283284
7.72	IC50	19	nM	CHEMBL5267968
6.62	IC50	242	nM	CHEMBL5277468
6.15	IC50	710	nM	CHEMBL5288393

PubChem BioAssay actives

4 with measured affinity, of 4 total; 4 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
2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-2-methyl-N-[5-[6-(trifluoromethyl)pyrazin-2-yl]-2-pyridinyl]propanamide	1935766: Inhibition of human CTPS2 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay	ic50	0.0180	uM
2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-N-[2-fluoro-4-[6-(trifluoromethyl)pyrazin-2-yl]phenyl]-2-methylpropanamide	1935766: Inhibition of human CTPS2 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay	ic50	0.0190	uM
2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-2-methyl-N-(4-pyridin-3-ylphenyl)propanamide	1935766: Inhibition of human CTPS2 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay	ic50	0.2420	uM
2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-2-methyl-N-(4-propoxyphenyl)propanamide	1935766: Inhibition of human CTPS2 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay	ic50	0.7100	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	9
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression, affects methylation	5
trichostatin A	affects cotreatment, decreases expression	2
Nickel	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
coumarin	increases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	affects cotreatment, decreases expression	1
Fulvestrant	increases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5239171	Binding	Inhibition of human CTPS2 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay	Discovery and Optimization of Potent and Orally Available CTP Synthetase Inhibitors for Use in Treatment of Diseases Driven by Aberrant Immune Cell Proliferation. — J Med Chem

Clinical trials (associated diseases)

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