PIR

Summary

PIR (pirin, HGNC:30048) is a protein-coding gene on chromosome Xp22.2, encoding Pirin (O00625). Transcriptional coregulator of NF-kappa-B which facilitates binding of NF-kappa-B proteins to target kappa-B genes in a redox-state-dependent manner.

This gene encodes a member of the cupin superfamily. The encoded protein is an Fe(II)-containing nuclear protein expressed in all tissues of the body and concentrated within dot-like subnuclear structures. Interactions with nuclear factor I/CCAAT box transcription factor as well as B cell lymphoma 3-encoded oncoprotein suggest the encoded protein may act as a transcriptional cofactor and be involved in the regulation of DNA transcription and replication. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 8544 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Limited, GenCC)
• Clinical variants (ClinVar): 33 total
• Druggable target: yes
• MANE Select transcript: NM_001018109

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30048
Approved symbol	PIR
Name	pirin
Location	Xp22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000087842
Ensembl biotype	protein_coding
OMIM	300931
Entrez	8544

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 21 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000380420, ENST00000380421, ENST00000471725, ENST00000476381, ENST00000484433, ENST00000492432, ENST00000909221, ENST00000909222, ENST00000909223, ENST00000909224, ENST00000909225, ENST00000909226, ENST00000909227, ENST00000909228, ENST00000909229, ENST00000909230, ENST00000932769, ENST00000932770, ENST00000932771, ENST00000946571, ENST00000946572, ENST00000946573, ENST00000946574, ENST00000946575, ENST00000946576

RefSeq mRNA: 2 — MANE Select: NM_001018109 NM_001018109, NM_003662

CCDS: CCDS14167

Canonical transcript exons

ENST00000380420 — 10 exons

Exon	Start	End
ENSE00001219767	15425906	15425990
ENSE00001484878	15493190	15493333
ENSE00003492353	15407506	15407550
ENSE00003505889	15397449	15397531
ENSE00003519794	15384799	15385116
ENSE00003534516	15390185	15390251
ENSE00003551232	15455848	15456054
ENSE00003597215	15459657	15459740
ENSE00003666312	15491162	15491309
ENSE00003691322	15479729	15479821

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 93.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.7935 / max 349.0947, expressed in 1706 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198530	17.5693	1678
198531	8.9706	1512
198532	0.2536	113

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	93.31	gold quality
lower esophagus mucosa	UBERON:0035834	92.84	gold quality
spinal cord	UBERON:0002240	91.84	gold quality
esophagus mucosa	UBERON:0002469	91.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.07	gold quality
right lung	UBERON:0002167	90.98	gold quality
right adrenal gland	UBERON:0001233	90.46	gold quality
right adrenal gland cortex	UBERON:0035827	90.26	gold quality
urinary bladder	UBERON:0001255	90.17	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.63	gold quality
left adrenal gland	UBERON:0001234	89.30	gold quality
esophagus	UBERON:0001043	89.15	gold quality
left adrenal gland cortex	UBERON:0035825	88.94	gold quality
islet of Langerhans	UBERON:0000006	88.85	gold quality
left coronary artery	UBERON:0001626	88.71	gold quality
descending thoracic aorta	UBERON:0002345	88.69	gold quality
ascending aorta	UBERON:0001496	88.59	gold quality
substantia nigra	UBERON:0002038	88.50	gold quality
thoracic aorta	UBERON:0001515	88.47	gold quality
adrenal tissue	UBERON:0018303	88.33	gold quality
right lobe of thyroid gland	UBERON:0001119	88.29	gold quality
epithelium of nasopharynx	UBERON:0001951	88.22	gold quality
omental fat pad	UBERON:0010414	88.22	gold quality
putamen	UBERON:0001874	88.21	gold quality
peritoneum	UBERON:0002358	88.17	gold quality
left lobe of thyroid gland	UBERON:0001120	88.12	gold quality
calcaneal tendon	UBERON:0003701	88.09	gold quality
coronary artery	UBERON:0001621	88.01	gold quality
right lobe of liver	UBERON:0001114	87.98	gold quality
adrenal cortex	UBERON:0001235	87.95	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.01
E-MTAB-5061	yes	5.77

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
NFKB1	Unknown

miRNA regulators (miRDB)

11 targeting PIR, 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-10523-5P	99.91	69.22	2038
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-100-3P	99.20	67.33	672
HSA-MIR-155-3P	99.03	67.99	924
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-5006-5P	98.79	66.92	1246

Literature-anchored findings (GeneRIF, showing 16)

• x-ray crystallography of of human pirin shows that it is an iron-binding nuclear protein and transcription cofactor (PMID:14573596)
• First report of enzymatic activity for any member of the Pirin family which may be an important connection to their roles in transcriptional regulation. (PMID:15951572)
• This study aimed to examine genetic variations in the PIR gene by a comprehensive tagging method and its sex-specific effects on bone mineral density and osteoporotic risk. (PMID:19766747)
• Pirin downregulation is a feature of acute myeloid leukemia and leads to impairment of terminal myeloid differentiation. (PMID:20010624)
• An abnormal pattern of PIR sub-cellular localization is a characteristic feature of a subset of melanomas, and suggest it may represent a marker associated with disease progression. (PMID:20089166)
• knockdown of pirin or treatment with the small molecule inhibited melanoma cell migration (PMID:20711196)
• pirin may have a relevant role in melanoma progression. (PMID:21514450)
• Data indicate that the R-shaped area composes the interface for pirin-NF-kappaB binding that is responsible for modulation of NF-kappaB’s DNA-binding properties. (PMID:23716661)
• Pirin is a newly identified binding partner of EAF2/U19 capable of down-regulating EAF2/U19 protein and alleviating its inhibition of prostate cancer cell survival/proliferation. (PMID:24272884)
• The NRF2 transcription factor binds to this element in vivo and drives the basal PIR expression. (PMID:24390086)
• Pirin regulates E-cadherin independently of Bcl3-Slug signaling. (PMID:25680527)
• Data suggest that only the Fe(III) form of pirin [not the Fe(II) form] enhances affinity of binding between p65 and DNA in the pirin-p65-DNA supramolecular complex. (pirin = quercetin 2,3-dioxygenase; p65 = RELA proto-oncogene NF-kappaB subunit) (PMID:28825294)
• miR-455-5p/PIR axis contributed to cancer cell aggressiveness. (PMID:30444038)
• PIR promotes tumorigenesis of breast cancer by upregulating cell cycle activator E2F1. (PMID:31500513)
• Pirin is a nuclear redox-sensitive modulator of autophagy-dependent ferroptosis. (PMID:33373853)
• PIWIL1 interacting RNA piR-017061 inhibits pancreatic cancer growth via regulating EFNA5. (PMID:33389678)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pir	ENSDARG00000056638
mus_musculus	Pir	ENSMUSG00000031379
rattus_norvegicus	Pir	ENSRNOG00000003674

Protein

Protein identifiers

Pirin — O00625 (reviewed: O00625)

Alternative names: Probable quercetin 2,3-dioxygenase PIR

All UniProt accessions (1): O00625

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional coregulator of NF-kappa-B which facilitates binding of NF-kappa-B proteins to target kappa-B genes in a redox-state-dependent manner. May be required for efficient terminal myeloid maturation of hematopoietic cells. Has quercetin 2,3-dioxygenase activity (in vitro).

Subunit / interactions. May interact with NF1/CTF1. Interacts with BCL3. Identified in a complex comprised of PIR, BLC3, NFKB1 and target DNA.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Highly expressed in a subset of melanomas. Detected at very low levels in most tissues (at protein level). Expressed in all tissues, with highest level of expression in heart and liver.

Activity regulation. Inhibited by kojic acid, sodium diethyldithiocarbamate and 1,10-phenanthroline monohydrochloride.

Cofactor. Binds 1 Fe cation per subunit.

Induction. Up-regulated in CD34(+) cells upon myelomonocytic differentiation. Down-regulated in many acute myeloid leukemias. Up-regulated in primary bronchial epithelial cells exposed to cigarette smoke extract.

Pathway. Flavonoid metabolism; quercetin degradation.

Polymorphism. Genetic variations in PIR might have a sex-specific influence on bone mineral density differences in some populations, as reported by PubMed:19766747. In a cohort of 4000 Chinese, a significant statistical association has been identified, in women but not in men, between the intronic SNP rs5935970 and lumbar spine bone mineral density, and between a haplotype composed of three SNPs with bone mineral density at other sites.

Similarity. Belongs to the pirin family.

RefSeq proteins (2): NP_001018119, NP_003653 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003829	Pirin_N_dom	Domain
IPR008778	Pirin_C_dom	Domain
IPR011051	RmlC_Cupin_sf	Homologous_superfamily
IPR012093	Pirin	Family
IPR014710	RmlC-like_jellyroll	Homologous_superfamily

Pfam: PF02678, PF05726

Catalyzed reactions (Rhea), 1 shown:

• quercetin + O2 = 2-(3,4-dihydroxybenzoyloxy)-4,6-dihydroxybenzoate + CO (RHEA:15381)

UniProt features (40 total): strand 25, helix 6, binding site 4, sequence conflict 2, chain 1, turn 1, sequence variant 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
6N0K	X-RAY DIFFRACTION	1.46
6H1H	X-RAY DIFFRACTION	1.54
4EWE	X-RAY DIFFRACTION	1.56
6H1I	X-RAY DIFFRACTION	1.69
4HLT	X-RAY DIFFRACTION	1.7
5JCT	X-RAY DIFFRACTION	1.73
6N0J	X-RAY DIFFRACTION	1.79
4GUL	X-RAY DIFFRACTION	1.8
1J1L	X-RAY DIFFRACTION	2.1
4EWD	X-RAY DIFFRACTION	2.15
3ACL	X-RAY DIFFRACTION	2.35
4EWA	X-RAY DIFFRACTION	2.47
4ERO	X-RAY DIFFRACTION	2.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00625-F1	97.11	0.99

Functional residue map

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

Ligand- & substrate-binding residues (4): 56; 58; 101; 103

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8935690	Digestion

MSigDB gene sets: 149 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_DIGESTION, MODULE_52, JI_RESPONSE_TO_FSH_UP, BENPORATH_ES_WITH_H3K27ME3, KAAB_FAILED_HEART_ATRIUM_DN, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, MODULE_308, MODULE_70, PATIL_LIVER_CANCER, MODULE_118, BROWNE_HCMV_INFECTION_48HR_DN, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, HOSHIDA_LIVER_CANCER_LATE_RECURRENCE_DN

GO Biological Process (4): transcription by RNA polymerase II (GO:0006366), digestion (GO:0007586), monocyte differentiation (GO:0030224), myeloid cell differentiation (GO:0030099)

GO Molecular Function (6): transcription coregulator activity (GO:0003712), quercetin 2,3-dioxygenase activity (GO:0008127), metal ion binding (GO:0046872), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), dioxygenase activity (GO:0051213)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear body (GO:0016604)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Digestion and absorption	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
DNA-templated transcription	1
multicellular organismal process	1
myeloid leukocyte differentiation	1
mononuclear cell differentiation	1
hemopoiesis	1
cell differentiation	1
transcription regulator activity	1
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen	1
cation binding	1
binding	1
catalytic activity	1
oxidoreductase activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
nucleoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1222 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIR	PIWIL4	Q7Z3Z4	981
PIR	PIWIL1	Q96J94	971
PIR	BCL3	P20749	966
PIR	PIWIL2	Q8TC59	942
PIR	CTF1	Q16619	910
PIR	AGO3	Q9H9G7	618
PIR	PIWIL3	Q7Z3Z3	597
PIR	MSN	P26038	597
PIR	RDX	P35241	580
PIR	NF1	P21359	568
PIR	EZR	P15311	520
PIR	IRS1	P35568	519
PIR	VSX2	P58304	516
PIR	ARHGAP11A	Q6P4F7	497
PIR	AKT1	P31749	495

IntAct

14 interactions, top by confidence:

A	B	Type	Score
C2orf68	PIR	psi-mi:“MI:0914”(association)	0.530
PIR	BCL3	psi-mi:“MI:0407”(direct interaction)	0.440
PIR	KHDRBS1	psi-mi:“MI:0915”(physical association)	0.400
SMAD9	PIR	psi-mi:“MI:0915”(physical association)	0.370
KLHL20	KRBA1	psi-mi:“MI:0914”(association)	0.350
FGB	NME2	psi-mi:“MI:0914”(association)	0.350
RIN3		psi-mi:“MI:0914”(association)	0.350
FGB	KIF2A	psi-mi:“MI:0914”(association)	0.350
PUF60	PIR	psi-mi:“MI:0914”(association)	0.350
INSR	UBXN8	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (94): PIR (Affinity Capture-RNA), PIR (Affinity Capture-MS), PIR (Affinity Capture-MS), ACAT2 (Co-fractionation), ADK (Co-fractionation), ANXA7 (Co-fractionation), ASS1 (Co-fractionation), C11orf54 (Co-fractionation), CFL1 (Co-fractionation), CFL2 (Co-fractionation), DCXR (Co-fractionation), DSTN (Co-fractionation), FAHD1 (Co-fractionation), FH (Co-fractionation), FUBP1 (Co-fractionation)

ESM2 similar proteins: A4RAE9, A5A6K3, A6SDE9, A7UWH7, B2AFW1, B2WMQ2, C7Z837, C9SDK8, D1ZQL9, D5GHP2, E3QYP0, E3S6N7, O00625, O04226, O08709, O35244, O65361, O77834, P29951, P34949, P37780, P54887, P54888, P58112, P73623, P93732, Q0U6G5, Q29554, Q2PFL9, Q3SZI0, Q5M827, Q5R7E0, Q5XGR8, Q66WM4, Q68FX1, Q6NYF0, Q6PI48, Q8HXX2, Q924M7, Q93Z70

Diamond homologs: O00625, P58112, P58113, P58114, P65725, P73623, P9WI84, P9WI85, Q5M827, Q9CKD7, Q9D711, Q9HLU2, Q9HZ00, Q9I163, Q9I4C8, Q9KKY1, Q9LPS9, Q9LX45, Q9LX49, Q9SEE4, Q9XBR7, Q9ZW82, P46852, P58116, Q9I4D3, P42624, P58115

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
NFE2L2	“up-regulates quantity by expression”	PIR	“transcriptional regulation”
PIR	“up-regulates activity”	NFE2L2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	0
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2629 predictions. Top by Δscore:

Variant	Effect	Δscore
X:15390252:C:CC	acceptor_gain	1.0000
X:15397445:TTA:T	donor_loss	1.0000
X:15397446:TA:T	donor_loss	1.0000
X:15397447:A:AC	donor_gain	1.0000
X:15397447:AC:A	donor_gain	1.0000
X:15397448:C:CC	donor_gain	1.0000
X:15397448:CC:C	donor_gain	1.0000
X:15397530:CCCTA:C	acceptor_loss	1.0000
X:15397531:CCT:C	acceptor_loss	1.0000
X:15397532:C:CC	acceptor_gain	1.0000
X:15410825:A:AC	donor_gain	1.0000
X:15410826:C:CC	donor_gain	1.0000
X:15455842:GCTTA:G	donor_loss	1.0000
X:15455843:CTTAC:C	donor_loss	1.0000
X:15455844:TTACC:T	donor_loss	1.0000
X:15455845:TACC:T	donor_loss	1.0000
X:15455846:A:C	donor_loss	1.0000
X:15479723:ACTT:A	donor_loss	1.0000
X:15479725:TTACT:T	donor_loss	1.0000
X:15479726:TACT:T	donor_loss	1.0000
X:15479727:A:AC	donor_gain	1.0000
X:15479728:C:CT	donor_gain	1.0000
X:15479728:CT:C	donor_gain	1.0000
X:15479728:CTG:C	donor_gain	1.0000
X:15479728:CTGT:C	donor_gain	1.0000
X:15479728:CTGTT:C	donor_gain	1.0000
X:15479817:TTTAA:T	acceptor_gain	1.0000
X:15479818:TTAA:T	acceptor_gain	1.0000
X:15479819:TAA:T	acceptor_gain	1.0000
X:15479819:TAAC:T	acceptor_loss	1.0000

AlphaMissense

1904 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:15455979:A:G	W117R	0.999
X:15455979:A:T	W117R	0.999
X:15456024:C:G	A102P	0.999
X:15479742:C:G	R59P	0.999
X:15479759:A:C	F53L	0.999
X:15479759:A:T	F53L	0.999
X:15479761:A:G	F53L	0.999
X:15385043:A:C	F278L	0.998
X:15385043:A:T	F278L	0.998
X:15385045:A:G	F278L	0.998
X:15385109:A:C	F256L	0.998
X:15385109:A:T	F256L	0.998
X:15385111:A:G	F256L	0.998
X:15479750:A:C	H56Q	0.998
X:15479750:A:T	H56Q	0.998
X:15479752:G:C	H56D	0.998
X:15385110:A:G	F256S	0.997
X:15455977:C:A	W117C	0.997
X:15455977:C:G	W117C	0.997
X:15456027:G:C	H101D	0.997
X:15456041:C:A	G96V	0.997
X:15456041:C:T	G96D	0.997
X:15459701:C:G	D77H	0.997
X:15479740:C:G	G60R	0.997
X:15479746:G:C	H58D	0.997
X:15491177:G:C	S27R	0.997
X:15491177:G:T	S27R	0.997
X:15491179:T:G	S27R	0.997
X:15491184:C:G	R25P	0.997
X:15390221:C:G	A242P	0.996

dbSNP variants (sampled 300 via entrez): RS1000007868 (X:15423613 C>A,G), RS1000016434 (X:15478689 G>A,C), RS1000023253 (X:15467367 G>T), RS1000033226 (X:15467932 G>T), RS1000066971 (X:15493061 A>G), RS1000098656 (X:15402823 T>A), RS1000145137 (X:15421556 T>A,C), RS1000159005 (X:15429734 T>C), RS1000194918 (X:15488002 G>A), RS1000195695 (X:15426085 C>T), RS1000220980 (X:15416945 T>A), RS1000253557 (X:15417303 A>G), RS1000265693 (X:15430572 C>A,G), RS1000307228 (X:15457663 T>G), RS1000533688 (X:15486157 C>T)

Disease associations

OMIM: gene MIM:300931 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	X-linked

Mondo (1): complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2010627 (SINGLE PROTEIN)

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

ChEMBL bioactivities

27 potent at pChembl≥5 of 27 total, top 27 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.75	Kd	18	nM	CHEMBL4099031
7.74	Kd	18.2	nM	CHEMBL4099031
7.57	Kd	27	nM	CHEMBL4063438
7.57	Kd	26.92	nM	CHEMBL4063438
7.57	Kd	27	nM	CHEMBL4077078
7.57	Kd	26.92	nM	CHEMBL4077078
7.55	Ki	28	nM	CHEMBL4087666
7.52	Kd	30.2	nM	CHEMBL4088624
7.52	Kd	30	nM	CHEMBL4088624
7.48	IC50	33	nM	CHEMBL4087666
7.48	IC50	33	nM	CHEMBL4473676
7.48	IC50	33.11	nM	CHEMBL4087666
7.42	Kd	38	nM	CHEMBL4070633
7.42	Kd	38.02	nM	CHEMBL4070633
7.42	Kd	38.02	nM	CHEMBL4096048
7.42	Kd	38	nM	CHEMBL4096048
7.36	Kd	43.65	nM	CHEMBL4087666
7.36	Kd	44	nM	CHEMBL4087666
7.36	IC50	44	nM	CHEMBL4070633
7.36	IC50	43.65	nM	CHEMBL4070633
6.72	Ki	190	nM	CHEMBL4096048
6.22	Kd	600	nM	CHEMBL1230119
6.17	IC50	670	nM	PLX-4720
5.82	AC50	1500	nM	CHEMBL4087666
5.77	Kd	1698	nM	CHEMBL1230119
5.77	Kd	1700	nM	CHEMBL1230119
5.00	AC50	1e+04	nM	CHEMBL4096048

PubChem BioAssay actives

25 with measured affinity, of 49 total; 10 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
N-[5-(3,4-dihydro-2H-chromene-6-carbonylamino)-2-methylphenyl]-2-methylquinoline-6-carboxamide	1434081: Binding affinity to recombinant human pirin by surface plasma resonance method	kd	0.0180	uM
N-[5-(3,4-dihydro-2H-chromene-7-carbonylamino)-2-methylphenyl]-2-methylquinoline-6-carboxamide	1434081: Binding affinity to recombinant human pirin by surface plasma resonance method	kd	0.0269	uM
N-[5-(3,4-dihydro-1H-isochromene-7-carbonylamino)-2-methylphenyl]-2-methylquinoline-6-carboxamide	1434081: Binding affinity to recombinant human pirin by surface plasma resonance method	kd	0.0269	uM
N-[5-(2,3-dihydro-1,4-benzodioxine-6-carbonylamino)-2-methylphenyl]-2-(2-pyrrolidin-1-ylethoxy)quinoline-6-carboxamide	1434104: Inhibition of bisamide probe binding to pirin in human SKOV3 cells by SILAC-based quantitative mass spectrometry pull down assay	ki	0.0280	uM
N-[5-(2,3-dihydro-1,4-benzodioxine-6-carbonylamino)-2-methylphenyl]-2-(3-piperidin-1-ylpropoxy)quinoline-6-carboxamide	1434081: Binding affinity to recombinant human pirin by surface plasma resonance method	kd	0.0300	uM
2-[(4-tert-butylpiperazin-1-yl)methyl]-N-[2-chloro-5-(2,3-dihydro-1,4-benzodioxine-6-carbonylamino)phenyl]quinoline-6-carboxamide	1533155: Displacement of 6-amino-9-(2-((4-((2-((6-((5-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)-2-methylphenyl)carbamoyl)quinolin-2-yl)oxy)ethyl)amino)-4-oxobutyl)(methyl)carbamoyl)phenyl)-3-imino-3H-xanthene-4,5-disulfonic acid from pirin (unknown origin) by fluorescence polarization assay	ic50	0.0330	uM
N-[5-(2,3-dihydro-1,4-benzodioxine-6-carbonylamino)-2-methylphenyl]-2-methylquinoline-6-carboxamide	1434081: Binding affinity to recombinant human pirin by surface plasma resonance method	kd	0.0380	uM
N-[5-(2,3-dihydro-1,4-benzodioxine-6-carbonylamino)-2-methylphenyl]-1,2,3,4-tetrahydroquinoline-6-carboxamide	1434081: Binding affinity to recombinant human pirin by surface plasma resonance method	kd	0.0380	uM
(NE)-4-methyl-N-[methyl-(4-phenylmethoxyphenyl)-lambda4-sulfanylidene]benzenesulfonamide	654201: Antagonist activity at pirin by ITC assay	kd	0.6000	uM
N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl]propane-1-sulfonamide	1533155: Displacement of 6-amino-9-(2-((4-((2-((6-((5-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)-2-methylphenyl)carbamoyl)quinolin-2-yl)oxy)ethyl)amino)-4-oxobutyl)(methyl)carbamoyl)phenyl)-3-imino-3H-xanthene-4,5-disulfonic acid from pirin (unknown origin) by fluorescence polarization assay	ic50	0.6700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	9
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases oxidation, increases expression	5
Valproic Acid	affects expression, increases expression	5
methylmercuric chloride	affects cotreatment, increases expression	4
bisphenol A	affects expression, decreases expression, increases expression, increases methylation	4
lead acetate	increases expression	4
Tobacco Smoke Pollution	increases expression	4
Cadmium Chloride	affects expression, increases expression	4
Aflatoxin B1	affects expression, decreases expression	3
arsenite	affects binding, increases reaction, increases abundance, increases expression	2
nickel sulfate	increases expression	2
mercuric bromide	affects cotreatment, increases expression	2
Arsenic Trioxide	increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Trinitrobenzenesulfonic Acid	increases expression	2
Isotretinoin	increases expression, decreases expression	2
Cyclosporine	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Particulate Matter	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
N(6)-(delta(2)-isopentenyl)adenine	increases expression	1
4-oxoretinoic acid	increases expression	1
tungsten carbide	affects cotreatment, increases expression	1
chloroacetaldehyde	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pirinixic acid	affects binding, increases activity, increases expression	1
cinnamaldehyde	increases expression	1

ChEMBL screening assays

5 unique, capped per target: 4 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2015225	Functional	Antagonist activity at pirin by ITC assay	Unbiased binding assays for discovering small-molecule probes and drugs. — Bioorg Med Chem
CHEMBL4001279	Binding	Binding affinity to recombinant human pirin by surface plasma resonance method	Discovery of a Chemical Probe Bisamide (CCT251236): An Orally Bioavailable Efficacious Pirin Ligand from a Heat Shock Transcription Factor 1 (HSF1) Phenotypic Screen. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder