MIF

Summary

MIF (macrophage migration inhibitory factor, HGNC:7097) is a protein-coding gene on chromosome 22q11.23, encoding Macrophage migration inhibitory factor (P14174). Pro-inflammatory cytokine involved in the innate immune response to bacterial pathogens.

This gene encodes a lymphokine involved in cell-mediated immunity, immunoregulation, and inflammation. It plays a role in the regulation of macrophage function in host defense through the suppression of anti-inflammatory effects of glucocorticoids. This lymphokine and the JAB1 protein form a complex in the cytosol near the peripheral plasma membrane, which may indicate an additional role in integrin signaling pathways.

Source: NCBI Gene 4282 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cystic fibrosis (Supportive, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 31 total
• GTEx eGene: eQTL in 0 tissues, sQTL in 2 (q < 0.05)
• Drug target: yes — 2 curated mechanism-of-action drugs; 10 molecules with ChEMBL bioactivity (top 3% of genes corpus-wide)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.96 (unconstrained)
• MANE Select transcript: NM_002415
• Interaction hub: 2,622 STRING partners (top 4% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7097
Approved symbol	MIF
Name	macrophage migration inhibitory factor
Location	22q11.23
Locus type	gene with protein product
Status	Approved
Aliases	GIF
Ensembl gene	ENSG00000240972
Ensembl biotype	protein_coding
OMIM	153620
Entrez	4282

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 retained_intron

MANE Select: ENST00000215754

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1

ENST00000215754, ENST00000465752, ENST00000498385, ENST00000857232, ENST00000921386, ENST00000921387, ENST00001131902

RefSeq mRNA: 1 — MANE Select: NM_002415 NM_002415

CCDS: CCDS13819

Canonical transcript exons

ENST00000215754 — 3 exons

Exon	Start	End
ENSE00001839840	23895040	23895223
ENSE00001922200	23894383	23894582
ENSE00003694118	23894772	23894944

Expression profiles

Bgee: expression breadth ubiquitous, 147 present calls, max score 99.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1122.0184 / max 6625.9934, expressed in 1825 samples.

Highest expression (Bgee): pituitary gland, adenohypophysis, cortex of kidney, adrenal gland, superior frontal gyrus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MIF is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 0 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

2 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellum	sqtl	1.1e-03	+0.82	22:23884703:G:A
Brain Cerebellar Hemisphere	sqtl	5.0e-03	+0.25	22:23942208:C:T

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
191342	1079.5071	1825
191343	32.1945	1801
191344	9.6381	1660
191345	0.6787	400

Top tissues by expression

showing 100 of 147 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	99.68	gold quality
adenohypophysis	UBERON:0002196	99.68	gold quality
cortex of kidney	UBERON:0001225	99.67	gold quality
right adrenal gland	UBERON:0001233	99.67	gold quality
left adrenal gland	UBERON:0001234	99.62	gold quality
superior frontal gyrus	UBERON:0002661	99.62	gold quality
metanephros cortex	UBERON:0010533	99.62	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.62	gold quality
lower esophagus mucosa	UBERON:0035834	99.62	gold quality
right uterine tube	UBERON:0001302	99.61	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.61	gold quality
left adrenal gland cortex	UBERON:0035825	99.61	gold quality
right adrenal gland cortex	UBERON:0035827	99.60	gold quality
hypothalamus	UBERON:0001898	99.59	gold quality
primary visual cortex	UBERON:0002436	99.59	gold quality
adult mammalian kidney	UBERON:0000082	99.58	gold quality
Ammon’s horn	UBERON:0001954	99.56	gold quality
right lobe of thyroid gland	UBERON:0001119	99.55	gold quality
esophagus mucosa	UBERON:0002469	99.55	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.55	gold quality
nucleus accumbens	UBERON:0001882	99.54	gold quality
left lobe of thyroid gland	UBERON:0001120	99.52	gold quality
temporal lobe	UBERON:0001871	99.52	gold quality
amygdala	UBERON:0001876	99.52	gold quality
anterior cingulate cortex	UBERON:0009835	99.52	gold quality
prostate gland	UBERON:0002367	99.50	gold quality
right frontal lobe	UBERON:0002810	99.50	gold quality
putamen	UBERON:0001874	99.48	gold quality
caudate nucleus	UBERON:0001873	99.46	gold quality
substantia nigra	UBERON:0002038	99.46	gold quality
mucosa of transverse colon	UBERON:0004991	99.46	gold quality
vagina	UBERON:0000996	99.44	gold quality
skin of abdomen	UBERON:0001416	99.43	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.42	gold quality
endocervix	UBERON:0000458	99.40	gold quality
skin of leg	UBERON:0001511	99.40	gold quality
ectocervix	UBERON:0012249	99.40	gold quality
lower esophagus	UBERON:0013473	99.40	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.40	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.39	gold quality
esophagus	UBERON:0001043	99.36	gold quality
left coronary artery	UBERON:0001626	99.36	gold quality
telencephalon	UBERON:0001893	99.35	gold quality
right ovary	UBERON:0002118	99.35	gold quality
cerebral cortex	UBERON:0000956	99.33	gold quality
fundus of stomach	UBERON:0001160	99.33	gold quality
body of stomach	UBERON:0001161	99.33	gold quality
ascending aorta	UBERON:0001496	99.33	gold quality
left ovary	UBERON:0002119	99.32	gold quality
left uterine tube	UBERON:0001303	99.31	gold quality
thoracic aorta	UBERON:0001515	99.31	gold quality
brain	UBERON:0000955	99.30	gold quality
body of pancreas	UBERON:0001150	99.28	gold quality
zone of skin	UBERON:0000014	99.27	gold quality
minor salivary gland	UBERON:0001830	99.26	gold quality
right lobe of liver	UBERON:0001114	99.25	gold quality
right atrium auricular region	UBERON:0006631	99.23	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.22	gold quality
artery	UBERON:0001637	99.19	gold quality
spleen	UBERON:0002106	99.18	gold quality
adrenal gland	UBERON:0002369	99.18	gold quality
saliva-secreting gland	UBERON:0001044	99.17	gold quality
right coronary artery	UBERON:0001625	99.17	gold quality
popliteal artery	UBERON:0002250	99.17	gold quality
tibial artery	UBERON:0007610	99.17	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.16	gold quality
mucosa of stomach	UBERON:0001199	99.13	gold quality
descending thoracic aorta	UBERON:0002345	99.13	gold quality
body of uterus	UBERON:0009853	99.13	gold quality
omental fat pad	UBERON:0010414	99.13	gold quality
thyroid gland	UBERON:0002046	99.11	gold quality
upper lobe of left lung	UBERON:0008952	99.10	gold quality
frontal cortex	UBERON:0001870	99.09	gold quality
frontal lobe	UBERON:0016525	99.09	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.08	gold quality
transverse colon	UBERON:0001157	99.07	gold quality
apex of heart	UBERON:0002098	99.03	gold quality
cerebellum	UBERON:0002037	99.01	gold quality
cerebellar cortex	UBERON:0002129	99.01	gold quality
cerebellar hemisphere	UBERON:0002245	99.00	gold quality
thoracic mammary gland	UBERON:0005200	99.00	gold quality
nerve	UBERON:0001021	98.99	gold quality
tibial nerve	UBERON:0001323	98.99	gold quality
mammary gland	UBERON:0001911	98.99	gold quality
right lung	UBERON:0002167	98.98	gold quality
colon	UBERON:0001155	98.95	gold quality
stromal cell of endometrium	CL:0002255	98.93	gold quality
adipose tissue	UBERON:0001013	98.93	gold quality
myometrium	UBERON:0001296	98.92	gold quality
cortical plate	UBERON:0005343	98.89	gold quality
ovary	UBERON:0000992	98.86	gold quality
small intestine	UBERON:0002108	98.86	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.86	gold quality
left testis	UBERON:0004533	98.86	gold quality
heart left ventricle	UBERON:0002084	98.84	gold quality
ganglionic eminence	UBERON:0004023	98.84	gold quality
embryo	UBERON:0000922	98.83	gold quality
right testis	UBERON:0004534	98.82	gold quality
ventricular zone	UBERON:0003053	98.81	gold quality
granulocyte	CL:0000094	98.78	gold quality

Single-cell (SCXA)

Detected in 32 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-ENAD-20	yes	3179.07
E-MTAB-8495	yes	2459.26
E-HCAD-38	yes	1949.03
E-GEOD-111727	yes	769.53
E-MTAB-10287	yes	34.24
E-ANND-3	yes	23.24
E-MTAB-9067	yes	20.94
E-CURD-112	yes	14.54
E-CURD-122	yes	11.91
E-MTAB-10042	yes	11.86
E-MTAB-7316	yes	9.28
E-MTAB-6678	yes	8.05
E-MTAB-9801	yes	6.28
E-GEOD-130148	yes	6.17
E-HCAD-35	yes	4.79

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 144 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	30401.1	high
Esophagus	tissue	21063.9	high
Vagina	tissue	13777.0	high
Tonsil	tissue	4098.7	high
Appendix	tissue	1418.6	not detected
Urinary bladder	tissue	890.9	not detected
Spleen	tissue	828.5	high
Pituitary gland	tissue	753.0
Vagina	tissue	658.3	low
Pons	tissue	643.1
Thalamus	tissue	612.5
Adipose tissue	tissue	579.9	not detected
Superior colliculi	tissue	579.9
Basal ganglia	tissue	539.8	low
Putamen	tissue	538.8
Cerebral cortex	tissue	530.5	medium
Somatosensory cortex	tissue	530.5
Midbrain	tissue	522.2
Spinal cord	tissue	510.1
Prefrontal cortex	tissue	505.0
Frontal cortex	tissue	505.0
Occipital cortex	tissue	504.1
Hippocampal formation	tissue	499.4
Motor cortex	tissue	486.9
Medulla oblongata	tissue	485.5
Hypothalamus	tissue	481.6
Substantia nigra	tissue	477.3
Septum	tissue	461.5
Retrosplenial and cingulate cortex	tissue	448.8
Smooth muscle	tissue	448.2	not detected
Temporal cortex	tissue	442.4
Ventral forebrain	tissue	439.2
Entorhinal cortex	tissue	437.3
Retrosplenial cortex	tissue	420.0
Periaqueductal gray	tissue	396.1
Locus coeruleus	tissue	380.3
Insular cortex	tissue	375.5
Choroid plexus	tissue	354.9
Cerebellum	tissue	354.4	low
Hippocampus	tissue	353.1	medium
Postcentral gyrus	tissue	351.0
Caudate putamen	tissue	347.5
Placenta	tissue	347.2	not detected
Amygdala	tissue	340.0
Nucleus accumbens	tissue	322.1
Olfactory bulb	tissue	270.6
Lung	tissue	240.2	medium
Corpus callosum	tissue	222.5
Thymus	tissue	184.3
Kidney	tissue	154.3	medium
Cervix	tissue	154.0	high
Skin 1	tissue	148.8	high
Tongue	tissue	140.2
Salivary gland	tissue	140.1	low
Adrenal gland	tissue	139.2	medium
Gallbladder	tissue	138.0	not detected
Bone marrow	tissue	137.5	low
Skin 1	tissue	136.3	low
Pancreas	tissue	136.2	medium
Liver	tissue	134.2	medium

Brain sub-regions (HPA Brain Atlas): detected in 479; highest nTPM — Lateral funiculus (white matter) (704.7), Blood vessel (582.3), Dorsal funiculus (white matter) (572.6), Arcuate nucleus (534.9), Anterior funiculus (white matter) (525.9).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting MIF by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

3 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-451A	91.68	64.18	71
HSA-MIR-1537-3P	90.51	63.57	105

Functional genomics

gnomAD constraint: pLI 2.27e-08, LOEUF 1.96, missense Z -2.72 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000215754 — one region, missense o/e 1.39.

Literature-anchored findings (GeneRIF, showing 40)

• increased expression seen in prostate carcinoma; may serve as prognostic marker (PMID:11920501)
• MIF is highly concentrated inside milk fat globules. milk MIF may protect the newborn against infection and play a role in preserving the functionality of the lactating mammary gland. (PMID:11978887)
• MIF seems to play a role in tumor-stroma interactions of primary breast cancers (PMID:11985788)
• role of tautomerase active site as target for discovery of novel anti-inflammatory agents (PMID:11997397)
• Monocyte chemotactic protein-1 and macrophage migration inhibitory factor production by peritoneal macrophages may contribute to paracrine and autocrine activation and to macrophage accumulation in peritoneal cavity of women with endometriosis. (PMID:12009356)
• a novel CATT-tetranucleotide repeat polymorphism correlated with low disease severity in a cohort of rheumatoid arthritis patients (PMID:12070782)
• capacity of MMIF to induce increased functional capacity of dendritic cells, and to produce IL-1beta and IL-8 from monocytes and DC, indicate a role of MMIF in the induction and/or perpetuation of the inflammatory environment in ulcerative colitis. (PMID:12109441)
• The serum level of MIF and PBMC MIF expression increased in acute respiratory distress syndrome patients (PMID:12126556)
• The MIF 173 C allele is associated with a significantly increased risk of developing sarcoidosis in patients with erythema nodosum. (PMID:12180727)
• released from lung epithelial cells rendered necrotic by influenza A virus infection (PMID:12186913)
• We found that the murine NB cell line, Neuro2a, secretes macrophage migration inhibitory factor, MIF, a multifunctional cytokine with the potential to block effective immune responses to a tumor (PMID:12218292)
• role of MIF in IgA nephropathy (PMID:12218308)
• Local and systemic up-regulation of MIF expression is associated with and precedes the occurrence of acute GVHD, suggesting a pathogenetic role. (PMID:12235522)
• The -173-MIF*C allele confers increased risk of susceptibility to juvenile idiopathic arthritis. (PMID:12355488)
• upregulation in intervillous blood is asociated with placental malaria (PMID:12402212)
• expression of MIF in human glioblastomas, a close relationship with VEGF expression. (PMID:12445161)
• Polymeric IgA increases the expression of this factor by human mesangial cells in IgA nephropathy. (PMID:12480958)
• up-regulation of MIF expression during hypoxic and hypoglycemic stress might play a critical role for the neovascularization of glial tumors (PMID:12507885)
• High levels of this factor are associated with risk of recurrernce after resection of lung cancer. (PMID:12576459)
• The increased secretion of MIF in AF at term, particularly at term labor, suggests that MIF contributes to the inflammatory events leading to labor. (PMID:12607777)
• Macrophage migration inhibitory factor is a critical mediator of severe acute pancreatitis. (PMID:12612911)
• Decreased serum MIF during early gestation were found in recurrent miscarriage with normal fetal chromosome karyotype. Might be related to aetiology of miscarriage. (PMID:12615835)
• MIF has potent anti-apoptotic activities and suppresses pro-oxidative stress-induced apoptosis. (PMID:12626594)
• The late morning peak of macrophage migration inhibitory factor, by antagonizing cortisol-mediated pro-inflammatory cytokine suppression may prolong the duration of early morning inflammation (PMID:12631237)
• Review. MIF is a critical upstream regulator of immune response. It is released under a variety of circumstances, regulates cytokine secretion & immune receptor expression, inhibits p53 function, & activates components of the MAP kinase & Jab-1 pathways. (PMID:12667094)
• interaction with apoptosis-associated protein BNIPL (PMID:12681488)
• the interaction between MIF and endotoxin may promote fluid collection in the middle ear, particularly in adults (PMID:12738641)
• MIF binds two peptides, hepatitis B surface antigen (HBsAg) and insulin B (InsB) with high affinity for HLA class II allo-types, HLA-DP2 and HLA-DQ8, respectively (PMID:12740374)
• Our study shows the functional relevance of the MIF-173 polymorphism and suggests that the MIF-173*C allele is a predictor of poor outcome in systemic-onset JIA. (PMID:12746913)
• MIF binds to the extracellular domain of CD74, and CD74 is required for MIF-induced activation of the extracellular signal-regulated kinase-1/2 MAP kinase cascade (PMID:12782713)
• MIF-(50-65) exhibits redox activity and has MIF-like biological functions (PMID:12796500)
• role for MIF in the regulation of p53 expression and p53-mediated events in the inflamed synovium and is of critical importance in the pathogenesis of RA. (PMID:12847682)
• Secretion of macrophage migration inhibitory factor is mediated by a non-classical pathway involving an ABCA1 transporter. (PMID:12965208)
• Macrophage migration inhibitory factor is a regulator of innate immunity. (PMID:14502271)
• MIF gene polymorphism is associated with susceptibility to but not severity of inflammatroy arthritis. (PMID:14551601)
• MIF is involved in the up-regulation of UVA-induced MMP-1 in dermal fibroblasts through PKC-, PKA-, Src family tyrosine kinase-, MAPK-, c-Jun-, and AP-1-dependent pathways. (PMID:14581488)
• MIF, TNF-alpha and IL-6 may participate in pathological process of chronic hepatitis B and cirrhosis. IL-6 may play important role in ascites formation. Serum MIF, TNF-alpha and IL-6 appear to reflect severity of tissue injury in hepatitis B. (PMID:14607690)
• MIF contributes to the inflammatory phase of the wound healing process in concert with thrombin and FXa via PAR-1 and PAR-2. (PMID:14736878)
• MIF is overexpressed in patients with systemic lupus erythematosus and while partly explained by corticosteroid use, there is evidence of an association between MIF and lupus-related disease damage. (PMID:14760795)
• MIF may play an important role in the migration of inflammatory cells into the synovium of rheumatoid joints via induction of IL-8. (PMID:15146413)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mif	ENSDARG00000071336
mus_musculus	Mif	ENSMUSG00000033307
rattus_norvegicus	Mif	ENSRNOG00000006589
rattus_norvegicus	Mifl2	ENSRNOG00000033673
rattus_norvegicus	AC127887.1	ENSRNOG00000034106
caenorhabditis_elegans		WBGENE00003234

Paralogs (2): DDTL (ENSG00000099974), DDT (ENSG00000099977)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:96982) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 20 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal inflammatory response	1
decreased susceptibility to bacterial infection	1
abnormal cochlear ganglion morphology	1
abnormal cytokine secretion	1
increased myocardial infarct size	1
decreased cochlear outer hair cell number	1
increased incidence of tumors by chemical induction	1
decreased incidence of tumors by chemical induction	1
abnormal outer hair cell stereociliary bundle morphology	1
decreased mitotic index	1
decreased eosinophil cell number	1
increased susceptibility to parasitic infection	1
impaired hearing	1
decreased circulating tumor necrosis factor level	1
increased interleukin-4 secretion	1
decreased susceptibility to endotoxin shock	1
increased fibrosarcoma incidence	1
decreased fibroblast proliferation	1
increased or absent threshold for auditory brainstem response	1
increased susceptibility to myocardial ischemic injury	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	P80177	100.0%	Diamond
Ovis aries	Q1ZZU7	100.0%	Diamond
Macaca fascicularis	Q4R549	100.0%	Diamond
Macaca mulatta	Q6DN04	100.0%	Diamond
Sus scrofa	P80928	94.8%	Diamond
Wuchereria bancrofti	O44786	93.9%	Diamond
Meriones unguiculatus	O55052	93.9%	Diamond
Brugia malayi	P91850	93.9%	Diamond
Xenopus tropicalis	A9JSE7	87.8%	Diamond
Xenopus laevis	Q76BK2	87.8%	Diamond
Onchocerca volvulus	Q963F7	86.1%	Diamond
Gallus gallus	Q02960	77.4%	Diamond
Trichinella spiralis	P81529	57.9%	Diamond
Trichuris trichiura	P81748	57.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIF-AS1	ncRNA	284889
GSTT2B	protein-coding	653689
SLC2A11	protein-coding	66035
DDTL	protein-coding	100037417
DDT	protein-coding	1652
MMP11	protein-coding	4320
SMARCB1	protein-coding	6598
DERL3	protein-coding	91319

Protein

Protein identifiers

Macrophage migration inhibitory factor — P14174 (reviewed: P14174)

Alternative names: Glycosylation-inhibiting factor, L-dopachrome isomerase, L-dopachrome tautomerase, Phenylpyruvate tautomerase

All UniProt accessions (2): P14174, I4AY87

UniProt curated annotations — full annotation on UniProt →

Function. Pro-inflammatory cytokine involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Counteracts the anti-inflammatory activity of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity.

Subunit / interactions. Homotrimer. Interacts with CXCR2 extracellular domain. Interacts with the CD74 extracellular domain, USO1, COPS5 and BNIPL.

Subcellular location. Secreted. Cytoplasm.

Disease relevance. Rheumatoid arthritis systemic juvenile (RASJ) [MIM:604302] An inflammatory articular disorder with systemic onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Induction. Up-regulated in concanavalin-A-treated lymphocytes. Up-regulated in macrophages upon exposure to M.tuberculosis antigens.

Miscellaneous. Serum levels of MIF are elevated in patients with severe sepsis or septic shock. High levels of MIF are correlated with low survival. Drugs that inhibit tautomerase activity protect against death due to sepsis.

Similarity. Belongs to the MIF family.

RefSeq proteins (1): NP_002406* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001398	Macrophage_inhib_fac	Family
IPR014347	Tautomerase/MIF_sf	Homologous_superfamily
IPR019829	Macrophage_inhib_fac_CS	Conserved_site

Pfam: PF01187

Enzyme classification (BRENDA)

• EC 5.3.2.1 — phenylpyruvate tautomerase (BRENDA: 15 organisms, 36 substrates, 162 inhibitors, 39 Km, 40 kcat entries)
• EC 5.3.3.12 — L-dopachrome isomerase (BRENDA: 15 organisms, 23 substrates, 32 inhibitors, 2 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ENOL-PHENYLPYRUVATE	0.02–0.31	14
ENOL-(P-HYDROXYPHENYL)PYRUVATE	0.107–0.582	8
(4-HYDROXYPHENYL)PYRUVATE	0.072–2.4	4
PHENYLENOLPYRUVATE	0.11–3.5	3
PHENYLPYRUVATE	6–8	3
(4-HYDROXYPHENYL)ENOLPYRUVATE	0.79–0.89	2
DOPACHROME	0.1–1	2
4-(HYDROXYPHENYL)PYRUVATE	0.1	1
CIS-3-CHLOROACRYLATE	0.152	1
KETO-(P-HYDROXYPHENYL)PYRUVATE	2.77	1
KETO-PHENYLPYRUVATE	4.9	1
TRANS-3-CHLOROACRYLATE	96	1

Catalyzed reactions (Rhea)

• L-dopachrome = 5,6-dihydroxyindole-2-carboxylate (RHEA:13041)
• 3-phenylpyruvate = enol-phenylpyruvate (RHEA:17097)

UniProt features (29 total): strand 7, sequence conflict 6, helix 6, binding site 3, modified residue 2, initiator methionine 1, chain 1, active site 1, turn 1, mutagenesis site 1

Structure

Experimental structures (PDB)

showing 30 of 119 structures by resolution:

PDB	Title	Method	Resolution (Å)
9JIT	Macrophage migration inhibitory factor S61H/Y100H mutant (MIF(S61H/Y100H))	X-RAY DIFFRACTION	1.08
9BNQ	N-(4-(isothiocyanatomethyl)phenyl)methanesulfonamide complexed with Macrophage Migration …	X-RAY DIFFRACTION	1.09
6B1K	Macrophage Migration Inhibitory Factor in Complex with a Naphthyridinone Inhibitor (3a)	X-RAY DIFFRACTION	1.17
9JIY	Macrophage migration inhibitory factor S61H/Y100H mutant complexed with three Zinc ions …	X-RAY DIFFRACTION	1.2
7EE8	The crystal structure of MIF bound to compound D5	X-RAY DIFFRACTION	1.22
3DJH	Macrophage Migration Inhibitory Factor (MIF) at 1.25 A Resolution	X-RAY DIFFRACTION	1.25
3IJJ	Ternary Complex of Macrophage Migration Inhibitory Factor (MIF) Bound Both to …	X-RAY DIFFRACTION	1.25
4GRN	crystal structure of PAAM mutant of human MIF	X-RAY DIFFRACTION	1.25
9JIV	Macrophage migration inhibitory factor Y100H mutant (MIF(Y100H))	X-RAY DIFFRACTION	1.25
9JJ0	Macrophage migration inhibitory factor Y100H mutant complexed with three Zinc ions …	X-RAY DIFFRACTION	1.25
7EDQ	MIF complex to compound7	X-RAY DIFFRACTION	1.27
4GRP	Crystallographic and biological characterization of N- and C- terminus mutants of human …	X-RAY DIFFRACTION	1.27
7XTX	High resolution crystal structure of human macrophage migration inhibitory factor in …	X-RAY DIFFRACTION	1.28
8IMR	Structure of ligand-free human macrophage migration inhibitory factor	X-RAY DIFFRACTION	1.3
9JIZ	Macrophage migration inhibitory factor S61H/Y100H mutant complexed with three Zinc ions …	X-RAY DIFFRACTION	1.3
5B4O	Crystal structure of Macrophage Migration Inhibitory Factor in complex with BTZO-14	X-RAY DIFFRACTION	1.37
7E47	Crystal structure of compound 6 bound to MIF	X-RAY DIFFRACTION	1.38
6FVH	Macrophage Migration Inhibitory Factor (MIF) with Covalently Bound PITC	X-RAY DIFFRACTION	1.4
6FVE	Macrophage Migration Inhibitory Factor (MIF) with Covalently Bound FITC	X-RAY DIFFRACTION	1.41
7E45	Crystal structure of compound 7 bound to MIF	X-RAY DIFFRACTION	1.43
4GRR	characterization of N- and C- terminus mutants of human MIF	X-RAY DIFFRACTION	1.47
7E4A	Crystal structure of MIF bound to compound 13	X-RAY DIFFRACTION	1.48
1GD0	HUMAN MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF)	X-RAY DIFFRACTION	1.5
4Z1T	MIF in complex with 4-[(4-oxo-2-thioxo-1,3-thiazolan-3-yl)methyl]benzonitrile	X-RAY DIFFRACTION	1.5
6BG6	Crystal structure of S111A mutant of human macrophage migration inhibitory factor	X-RAY DIFFRACTION	1.52
4F2K	Macrophage Migration Inhibitory Factor covalently complexed with phenethylisothiocyanate	X-RAY DIFFRACTION	1.53
6OY8	Crystal structure of Y99G mutant of human macrophage migration inhibitory factor	X-RAY DIFFRACTION	1.53
6OYB	Crystal structure of H62G mutant of human macrophage migration inhibitory factor	X-RAY DIFFRACTION	1.53
6OYE	Crystal structure of Y99F mutant of human macrophage migration inhibitory factor	X-RAY DIFFRACTION	1.53
9BNR	4-(2-isothiocyanatoethyl)benzenesulfonamide complexed with Macrophage Migration …	X-RAY DIFFRACTION	1.53

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14174-F1	98.60	1.00

Human Protein Atlas

Protein class: Predicted secreted proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; intermediate filaments; plasma membrane

Antibody reliability (HPA): IH enhanced · IF supported

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 (1)

Position	Role
2	proton acceptor; via imino nitrogen

Ligand- & substrate-binding residues (3)

Position	Role
33	substrate
65	substrate
98	substrate

Post-translational modifications (2)

Type	Positions
N6-acetyllysine	78
N6-succinyllysine	78

Mutagenesis-validated functional residues (1)

Position	Phenotype
111	causes formation of interchain disulfide bonds with cys-81 from another subunit.

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 10; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

10 pathways:

ID	Pathway	Evidence
R-HSA-202733	Cell surface interactions at the vascular wall	curated
R-HSA-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	curated
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-109582	Hemostasis	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-447115	Interleukin-12 family signaling	—
R-HSA-9020591	Interleukin-12 signaling	—
R-HSA-449147	Signaling by Interleukins	—

MSigDB gene sets: 564 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_ICOSANOID_SECRETION, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, GOBP_B_CELL_HOMEOSTASIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, HARRIS_HYPOXIA, GOBP_CELL_CHEMOTAXIS, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_BY_P53_CLASS_MEDIATOR, GOBP_REGULATION_OF_PROSTAGLANDIN_SECRETION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM

GO Biological Process (35): prostaglandin biosynthetic process (GO:0001516), positive regulation of cytokine production (GO:0001819), negative regulation of mature B cell apoptotic process (GO:0002906), inflammatory response (GO:0006954), cell surface receptor signaling pathway (GO:0007166), positive regulation of cell population proliferation (GO:0008284), negative regulation of gene expression (GO:0010629), negative regulation of macrophage chemotaxis (GO:0010760), carboxylic acid metabolic process (GO:0019752), negative regulation of cell migration (GO:0030336), positive regulation of B cell proliferation (GO:0030890), positive regulation of lipopolysaccharide-mediated signaling pathway (GO:0031666), positive regulation of tumor necrosis factor production (GO:0032760), negative regulation of myeloid cell apoptotic process (GO:0033033), positive regulation of phosphorylation (GO:0042327), regulation of macrophage activation (GO:0043030), negative regulation of apoptotic process (GO:0043066), negative regulation of DNA damage response, signal transduction by p53 class mediator (GO:0043518), innate immune response (GO:0045087), positive regulation of fibroblast proliferation (GO:0048146), negative regulation of protein metabolic process (GO:0051248), positive regulation of myeloid leukocyte cytokine production involved in immune response (GO:0061081), protein homotrimerization (GO:0070207), positive regulation of ERK1 and ERK2 cascade (GO:0070374), positive regulation of arachidonate secretion (GO:0090238), positive regulation of cAMP/PKA signal transduction (GO:0141163), negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:1902166), positive regulation of chemokine (C-X-C motif) ligand 2 production (GO:2000343), negative regulation of cellular senescence (GO:2000773), immune system process (GO:0002376), signal transduction (GO:0007165), positive regulation of prostaglandin secretion (GO:0032308), positive regulation of innate immune response (GO:0045089), positive chemotaxis (GO:0050918), regulation of cellular response to stress (GO:0080135)

GO Molecular Function (9): protease binding (GO:0002020), dopachrome isomerase activity (GO:0004167), cytokine activity (GO:0005125), cytokine receptor binding (GO:0005126), chemoattractant activity (GO:0042056), identical protein binding (GO:0042802), phenylpyruvate tautomerase activity (GO:0050178), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (9): extracellular region (GO:0005576), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cell surface (GO:0009986), vesicle (GO:0031982), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

7 top-level categories:

Category	Pathways
Immune System	2
Hemostasis	1
Innate Immune System	1
Interleukin-12 signaling	1
Signaling by Interleukins	1
Cytokine Signaling in Immune system	1
Interleukin-12 family signaling	1

GO top-level categories

showing 60 of 76 GO namespaces:

Category	Terms
cellular anatomical structure	4
receptor ligand activity	2
prostaglandin metabolic process	1
prostanoid biosynthetic process	1
cytokine production	1
regulation of cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
mature B cell apoptotic process	1
negative regulation of B cell apoptotic process	1
regulation of mature B cell apoptotic process	1
defense response	1
signal transduction	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
negative regulation of leukocyte chemotaxis	1
regulation of macrophage chemotaxis	1
macrophage chemotaxis	1
negative regulation of macrophage migration	1
oxoacid metabolic process	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
regulation of B cell proliferation	1
B cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of B cell activation	1
positive regulation of response to biotic stimulus	1
positive regulation of signal transduction	1
lipopolysaccharide-mediated signaling pathway	1
regulation of lipopolysaccharide-mediated signaling pathway	1
positive regulation of response to external stimulus	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
myeloid cell apoptotic process	1
regulation of myeloid cell apoptotic process	1
negative regulation of apoptotic process	1
phosphorylation	1
regulation of phosphorylation	1
positive regulation of phosphate metabolic process	1
regulation of leukocyte activation	1
macrophage activation	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
DNA damage response, signal transduction by p53 class mediator	1
regulation of DNA damage response, signal transduction by p53 class mediator	1
negative regulation of signal transduction by p53 class mediator	1
immune response	1
defense response to symbiont	1
positive regulation of cell population proliferation	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
enzyme binding	1
intramolecular oxidoreductase activity, transposing C=C bonds	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 32 of 55 annotations. The rest are phylogenetic / computational / electronic (IEA).

32 experimentally-supported GO terms:

GO term	NS	Evidence
carboxylic acid metabolic process	BP	direct assay
cell surface receptor signaling pathway	BP	direct assay
negative regulation of DNA damage response, signal transduction by p53 class mediator	BP	direct assay
negative regulation of apoptotic process	BP	direct assay
negative regulation of cell migration	BP	mutant phenotype
negative regulation of cellular senescence	BP	direct assay
negative regulation of gene expression	BP	direct assay
negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	BP	direct assay
negative regulation of macrophage chemotaxis	BP	direct assay
positive regulation of B cell proliferation	BP	direct assay
positive regulation of ERK1 and ERK2 cascade	BP	direct assay
positive regulation of cAMP/PKA signal transduction	BP	direct assay
positive regulation of cell population proliferation	BP	direct assay
positive regulation of cytokine production	BP	direct assay
positive regulation of fibroblast proliferation	BP	direct assay
positive regulation of phosphorylation	BP	direct assay
positive regulation of tumor necrosis factor production	BP	direct assay
prostaglandin biosynthetic process	BP	direct assay
protein homotrimerization	BP	physical interaction
cell surface	CC	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
extracellular exosome	CC	high-throughput assay
extracellular region	CC	direct assay
plasma membrane	CC	direct assay
vesicle	CC	high-throughput assay
chemoattractant activity	MF	direct assay
cytokine activity	MF	direct assay
cytokine receptor binding	MF	direct assay
dopachrome isomerase activity	MF	direct assay
identical protein binding	MF	physical interaction
phenylpyruvate tautomerase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,622 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MIF	CD74	P04233	899
MIF	COPS5	Q92905	735
MIF	CXCR2	P25025	708
MIF	CXCR4	P30991	700
MIF	IL6	P05231	690
MIF	IL1B	P01584	666
MIF	TNF	P01375	660
MIF	CCL2	P13500	649
MIF	CXCL8	P10145	648
MIF	IL10	P22301	631
MIF	IFNG	P01579	589
MIF	TGFB1	P01137	570
MIF	CXCL12	P48061	556
MIF	CCL5	P13501	548
MIF	IL1A	P01583	540

IntAct

Human interaction partners of MIF in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 33 partners by confidence:

Partner	Interaction type	MIscore	Records
NTAQ1	physical association	0.670	4
COPS5	physical association	0.590	3
EGFR	physical association	0.590	3
BCL2L11	physical association	0.580	9
GCD7	physical association	0.560	3
HTRA1	physical association	0.530	3
CXCR2	direct interaction	0.440	1
COPS6	physical association	0.400	1
BEX3	physical association	0.370	1
BNIPL	physical association	0.370	1
GORASP2	physical association	0.370	1
BLTP3B	association	0.350	1
PDHX	association	0.350	1
ATG5	physical association	0.000	1
CFLAR	physical association	0.000	1
DSTYK	physical association	0.000	1
EIF1B	physical association	0.000	1
EPB41	physical association	0.000	1
FBXO11	physical association	0.000	1
FIBP	physical association	0.000	1
FTSJ1	physical association	0.000	1
HLA-B	physical association	0.000	1
IKBKE	physical association	0.000	1
ILK	physical association	0.000	1
MPG	physical association	0.000	1
PINX1	physical association	0.000	1
PRKAB1	physical association	0.000	1
STRN4	physical association	0.000	1
TNFRSF10D	physical association	0.000	1
TNFRSF14	physical association	0.000	1

BioGRID (358 interactions; top human partners by supporting records): COPS5 (Affinity Capture-Western; 7 records), BNIPL (Two-hybrid; 4 records), ENO1 (Co-fractionation; 4 records), NME1 (Affinity Capture-Western; 3 records), CCNF (Proximity Label-MS; 2 records), CD74 (Reconstituted Complex; 2 records), EGFR (Reconstituted Complex; 2 records), GAPDH (Cross-Linking-MS (XL-MS); 2 records), HIF1A (Affinity Capture-Western; 2 records), HIST1H2BB (Affinity Capture-MS; 2 records), HSPE1 (Affinity Capture-MS; 2 records), MCM2 (Affinity Capture-MS; 2 records), MYC (Affinity Capture-MS; 2 records), PARK2 (Affinity Capture-MS; 2 records), PARK7 (Co-fractionation; 2 records)

SIGNOR signaling

7 signaling interactions:

A	Effect	B	Mechanism
MIF	up-regulates	CD74	binding
MIF	“down-regulates quantity by repression”	HBB	“transcriptional regulation”
MIF	“down-regulates quantity by repression”	HBA1	“transcriptional regulation”
MIF	“up-regulates activity”	CD74	binding
MIF	“up-regulates activity”	CXCR2	binding
MIF	“up-regulates activity”	CXCR4	binding
MIF	“down-regulates quantity by destabilization”	SOD1	relocalization

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
MIF-NME1 complex	2	MIF, NME1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 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
negative regulation of apoptotic process	7	7.6×	1e-02

Disease & clinical

Genetic variants

Variant evidence for MIF: 31 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	4
Benign	0

AlphaMissense

283 missense substitutions predicted likely pathogenic (of 755 scored), across 79 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F114	8	0.952	0.994
N73	8	0.893	0.950
W109	7	0.943	0.970
R94	7	0.928	0.984
F50	7	0.908	0.982
D101	7	0.809	0.911
K33	6	0.975	0.988
P2	6	0.953	0.981
G66	6	0.913	0.982
N9	6	0.902	0.987
S64	6	0.900	0.989
S77	6	0.896	0.989
V107	6	0.896	0.982
C60	6	0.890	0.990
G108	6	0.882	0.987
C57	6	0.837	0.983
M48	6	0.823	0.931
T113	6	0.778	0.860
Y37	5	0.938	0.964
Y96	5	0.901	0.975

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma, Head and Neck Squamous Cell Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

8 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	6.94e-06
Liver Hepatocellular Carcinoma (validation)	unfavorable	5.9e-05
Lung Adenocarcinoma (TCGA)	unfavorable	8.93e-05
Glioblastoma Multiforme (TCGA)	unfavorable	0.000206
Glioblastoma Multiforme (validation)	favorable	0.000278
Lung Squamous Cell Carcinoma (validation)	unfavorable	0.000289
Lung Adenocarcinoma (validation)	unfavorable	0.000675
Head and Neck Squamous Cell Carcinoma (TCGA)	unfavorable	0.000758

Disease associations

OMIM: gene MIM:153620 | disease phenotypes:

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
cystic fibrosis	Supportive	Autosomal recessive
juvenile idiopathic arthritis	Limited	Autosomal dominant

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 0 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
COVID-19 research	amber

Mondo (2): cystic fibrosis (MONDO:0009061), juvenile idiopathic arthritis (MONDO:0011429)

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D001171	Arthritis, Juvenile	C05.550.114.122; C05.799.056; C17.300.775.049; C20.111.198
D003550	Cystic Fibrosis	C06.689.202; C08.381.187; C16.320.190; C16.614.213

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2085 (SINGLE PROTEIN), CHEMBL2111430 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193804 (PROTEIN-PROTEIN INTERACTION)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the MIF protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

2 curated-mechanism drugs:

Drug	Modality	Max phase
IGURATIMOD	Small molecule	3
IMALUMAB	Antibody	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 277,412 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

10 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL496	HEXACHLOROPHENE	4	26,440
CHEMBL90	HISTAMINE	4	170,520
CHEMBL19449	IBUDILAST	4	7,547
CHEMBL1201319	METARAMINOL	4	3,819
CHEMBL2107455	IGURATIMOD	3	1,482
CHEMBL51085	EBSELEN	3	13,356
CHEMBL48802	SULFORAPHANE	3	8,132
CHEMBL6246	ELLAGIC ACID	2	23,439
CHEMBL1627201	L-SULFORAPHANE	2	49
CHEMBL233248	ALLYL ISOTHIOCYANATE	1	22,628

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

519 measured of 583 human assays (604 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[3-methoxy-4-[(5-thiophen-2-yl-1,3,4-oxadiazol-2-yl)carbamoyl]phenyl]piperidine-3-carboxylic acid	IC50	6.92 nM	US-11884682: Compounds and their uses as MIF inhibitors
4-[3-methoxy-4-[(5-thiophen-2-yl-1,3,4-oxadiazol-2-yl)carbamoyl]phenyl]cyclohex-3-ene-1-carboxylic acid	IC50	7.24 nM	US-11884682: Compounds and their uses as MIF inhibitors
3-(3-hydroxybenzyl)-6-methylbenzo[d]oxazol-2(3H)-one	IC50	7.5 nM
2-[3-methoxy-4-[(5-thiophen-2-yl-1,3,4-oxadiazol-2-yl)carbamoyl]anilino]-2-methylpropanoic acid	IC50	9.55 nM	US-11884682: Compounds and their uses as MIF inhibitors
3-(3-hydroxybenzyl)-5-methylbenzo[d]oxazol-2(3H)-one	IC50	10 nM
4-(2-hydroxyethoxy)-2-methoxy-N-(5-thiophen-2-yl-1,3,4-oxadiazol-2-yl)benzamide	IC50	10.5 nM	US-11884682: Compounds and their uses as MIF inhibitors
2-methoxy-4-[3-(2H-tetrazol-5-yl)propyl]-N-(5-thiophen-2-yl-1,3,4-oxadiazol-2-yl)benzamide	IC50	11.2 nM	US-11884682: Compounds and their uses as MIF inhibitors
2-methoxy-4-(2H-tetrazol-5-ylmethoxy)-N-(5-thiophen-2-yl-1,3,4-oxadiazol-2-yl)benzamide	IC50	12.3 nM	US-11884682: Compounds and their uses as MIF inhibitors
1-[3-methoxy-4-[(5-thiophen-2-yl-1,3,4-oxadiazol-2-yl)carbamoyl]phenyl]pyrrolidine-2-carboxylic acid	IC50	12.6 nM	US-11884682: Compounds and their uses as MIF inhibitors
3-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-5-yl]oxybenzoic acid	KI	14 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
2,4-dimethoxy-N-(5-thiophen-3-yl-1,3,4-oxadiazol-2-yl)benzamide	IC50	18.6 nM	US-11884682: Compounds and their uses as MIF inhibitors
4-[3-methoxy-4-[(5-thiophen-2-yl-1,3,4-oxadiazol-2-yl)carbamoyl]phenyl]cyclohexane-1-carboxylic acid	IC50	18.6 nM	US-11884682: Compounds and their uses as MIF inhibitors
4-(3-cyanopropyl)-2-methoxy-N-(5-thiophen-2-yl-1,3,4-oxadiazol-2-yl)benzamide	IC50	20.9 nM	US-11884682: Compounds and their uses as MIF inhibitors
2,4-dimethoxy-N-(5-thiophen-2-yl-1,3,4-oxadiazol-2-yl)benzamide	IC50	22.9 nM	US-11884682: Compounds and their uses as MIF inhibitors
2-methoxy-4-(2-phenylmethoxyethoxy)-N-(5-thiophen-2-yl-1,3,4-oxadiazol-2-yl)benzamide	IC50	23.4 nM	US-11884682: Compounds and their uses as MIF inhibitors
2-fluoro-4-[4-[5-[3-(2-methoxyethoxy)phenoxy]quinolin-2-yl]triazol-1-yl]phenol	KI	24 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
2-[3-methoxy-4-[(5-thiophen-2-yl-1,3,4-oxadiazol-2-yl)carbamoyl]phenoxy]-2-methylpropanoic acid	IC50	25.7 nM	US-11884682: Compounds and their uses as MIF inhibitors
2-[3-methoxy-4-[(5-thiophen-2-yl-1,3,4-oxadiazol-2-yl)carbamoyl]phenoxy]acetic acid	IC50	28.8 nM	US-11884682: Compounds and their uses as MIF inhibitors
2-methoxy-4-[[2-[(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl]tetrazol-5-yl]methoxy]-N-(5-thiophen-2-yl-1,3,4-oxadiazol-2-yl)benzamide	IC50	31.6 nM	US-11884682: Compounds and their uses as MIF inhibitors
3-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-6-yl]oxypropyl formate	KI	34 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
2-methoxy-4-morpholin-4-yl-N-(5-thiophen-2-yl-1,3,4-oxadiazol-2-yl)benzamide	IC50	36.3 nM	US-11884682: Compounds and their uses as MIF inhibitors
2-[2-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-6-yl]oxyethoxy]acetic acid	KI	37 nM	US-10968198: Biaryltriazole inhibitors of macrophage migration inhibitory factor
3-(3,4-dihydroxyphenyl)-4H-chromen-4-one	IC50	38 nM
4-[3-methoxy-4-[(5-thiophen-2-yl-1,3,4-oxadiazol-2-yl)carbamoyl]phenyl]cyclohexane-1-carboxylic acid	IC50	38 nM	US-11884682: Compounds and their uses as MIF inhibitors
3-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-7-yl]oxypropyl formate	KI	43 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
4-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-7-yl]oxybutanoic acid	KI	43 nM	US-10968198: Biaryltriazole inhibitors of macrophage migration inhibitory factor
2-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-6-yl]oxyethoxymethyl formate	KI	45 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor
2-methoxy-4-morpholin-4-yl-N-[5-(1,3-thiazol-5-yl)-1,3,4-oxadiazol-2-yl]benzamide	IC50	46.8 nM	US-11884682: Compounds and their uses as MIF inhibitors
CHEMBL3899123	KI	48 nM
2-methoxy-4-[[1-[(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl]tetrazol-5-yl]methoxy]-N-(5-thiophen-2-yl-1,3,4-oxadiazol-2-yl)benzamide	IC50	49 nM	US-11884682: Compounds and their uses as MIF inhibitors
6-phenylpyridazin-3-yl thiophene-2-carboxylate	IC50	50 nM
CHEMBL5591863	KI	51 nM
2-methoxy-4-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)-N-(5-thiophen-2-yl-1,3,4-oxadiazol-2-yl)benzamide	IC50	51.3 nM	US-11884682: Compounds and their uses as MIF inhibitors
CHEMBL5589606	KI	55 nM
CHEMBL5594739	KI	55 nM
CHEMBL4208992	KI	56 nM
4-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-6-yl]oxybutanoic acid	KD	63 nM	US-10968198: Biaryltriazole inhibitors of macrophage migration inhibitory factor
CHEMBL5590917	KI	65 nM
2-(4-cyclopropyl-7-ethylnaphthalen-2-yl)oxy-5-(5-fluoro-1H-pyrazol-4-yl)benzoic acid	KI	66 nM	US-11999723: Pyrazole-containing macrophage migration inhibitory factor inhibitors
5-(5-fluoro-1H-pyrazol-4-yl)-2-[3-[4-(3-morpholin-4-ylpropoxy)phenyl]phenoxy]benzoic acid	KI	67 nM	US-11999723: Pyrazole-containing macrophage migration inhibitory factor inhibitors
2,4-dimethoxy-N-[5-(1,3-thiazol-5-yl)-1,3,4-oxadiazol-2-yl]benzamide	IC50	67.6 nM	US-11884682: Compounds and their uses as MIF inhibitors
CHEMBL5592539	KI	71 nM
2-[3-(4-ethoxyphenyl)phenoxy]-5-(5-fluoro-1H-pyrazol-4-yl)benzoic acid	KI	75 nM	US-11999723: Pyrazole-containing macrophage migration inhibitory factor inhibitors
cid_10414856	IC50	80 nM
4-hydroxy-2-methoxy-N-(5-thiophen-2-yl-1,3,4-oxadiazol-2-yl)benzamide	IC50	81.3 nM	US-11884682: Compounds and their uses as MIF inhibitors
CHEMBL5583909	KI	86 nM
CHEMBL4170679	KD	94 nM
CHEMBL4094592	KI	100 nM
2-(1,2-dihydroacenaphthylen-4-yloxy)-5-(5-fluoro-1H-pyrazol-4-yl)benzoic acid	KI	100 nM	US-11999723: Pyrazole-containing macrophage migration inhibitory factor inhibitors
4-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-5-yl]oxybenzoic acid	KI	110 nM	US-10336721: Biaryltriazole inhibitors of macrophage migration inhibitory factor

ChEMBL bioactivities

449 potent at pChembl≥5 of 698 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.02	Ki	0.96	nM	CHEMBL4763772
8.72	Kd	1.918	nM	CHEMBL3752910
8.65	ED50	2.239	nM	CHEMBL3752910
8.12	IC50	7.5	nM	CHEMBL1256233
8.00	IC50	10	nM	CHEMBL1255975
7.85	Ki	14	nM	CHEMBL3917143
7.80	Kd	16	nM	CHEMBL4779696
7.64	Ki	23	nM	CHEMBL3917143
7.62	Ki	24	nM	CHEMBL3918231
7.47	Ki	34	nM	CHEMBL5999957
7.47	Ki	34	nM	CHEMBL3927658
7.43	Ki	37	nM	CHEMBL3890541
7.42	Ki	38	nM	CHEMBL13486
7.42	IC50	38	nM	CHEMBL13486
7.42	IC50	38	nM	CHEMBL1089054
7.41	Ki	39	nM	CHEMBL3927658
7.37	Ki	43	nM	CHEMBL5936436
7.37	Ki	43	nM	CHEMBL5784808
7.35	Ki	45	nM	CHEMBL5987981
7.35	Ki	45	nM	CHEMBL3890541
7.32	Ki	48	nM	CHEMBL3899123
7.30	IC50	50	nM	CHEMBL1253380
7.29	Ki	51	nM	CHEMBL5591863
7.28	Ki	52	nM	CHEMBL3797437
7.26	Ki	55	nM	CHEMBL5589606
7.26	Ki	55	nM	CHEMBL5594739
7.25	Ki	56	nM	CHEMBL4208992
7.24	Ki	57	nM	CHEMBL3917143
7.20	Kd	63	nM	CHEMBL3927658
7.19	Ki	65	nM	CHEMBL5590917
7.17	Ki	67	nM	CHEMBL4208079
7.16	Kd	68.6	nM	BTZO-1
7.15	Ki	71	nM	CHEMBL4779696
7.15	Ki	71	nM	CHEMBL5592539
7.15	IC50	71	nM	BTZO-1
7.13	Ki	74	nM	CHEMBL3957289
7.12	Ki	75	nM	CHEMBL4160035
7.10	IC50	80	nM	CHEMBL1253382
7.10	IC50	80	nM	CHEMBL1256304
7.09	Ki	82	nM	CHEMBL3918231
7.07	Ki	86	nM	CHEMBL5583909
7.06	Kd	88	nM	BTZO-1
7.05	Ki	90	nM	CHEMBL4170679
7.05	IC50	90	nM	CHEMBL1255976
7.03	Kd	94	nM	CHEMBL4170679
7.00	Ki	100	nM	CHEMBL4094592
7.00	Ki	100	nM	CHEMBL4794376
6.96	IC50	110	nM	CHEMBL3797982
6.96	Kd	111	nM	CHEMBL4160035
6.96	Kd	110	nM	CHEMBL4794376

PubChem BioAssay actives

403 with measured affinity, of 1280 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
5-chloro-N-[[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]methyl]-1H-indole-2-carboxamide	2276615: Binding affinity to human MIF using HPP as substrate assessed as inhibition constant	ki	0.0010	uM
N-[[1-(4-hydroxyphenyl)triazol-4-yl]methyl]-1H-indole-2-carboxamide	2276615: Binding affinity to human MIF using HPP as substrate assessed as inhibition constant	ki	0.0010	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148750: Binding affinity to human MIF incubated for 45 mins by Kinobead based pull down assay	kd	0.0019	uM
N-[[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]methyl]-1H-indole-2-carboxamide	2276615: Binding affinity to human MIF using HPP as substrate assessed as inhibition constant	ki	0.0033	uM
3-[(3-hydroxyphenyl)methyl]-6-methyl-1,3-benzoxazol-2-one	516521: Inhibition of human recombinant MIF tautomerase	ic50	0.0075	uM
3-[(3-hydroxyphenyl)methyl]-5-methyl-1,3-benzoxazol-2-one	516521: Inhibition of human recombinant MIF tautomerase	ic50	0.0100	uM
3-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-5-yl]oxybenzoic acid	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.0140	uM
4-[4-(7-hydroxy-2-oxochromen-3-yl)phenyl]benzoic acid	1697392: Binding affinity to C-terminal His-tagged recombinant human MIF expressed in Escherichia coli BL21 (DE3) at 200 nM by fluorescence assay	kd	0.0160	uM
2-fluoro-4-[4-[5-[3-(2-methoxyethoxy)phenoxy]quinolin-2-yl]triazol-1-yl]phenol	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.0240	uM
2-[2-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-6-yl]oxyethoxy]acetic acid	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.0370	uM
3-(3,4-dihydroxyphenyl)chromen-4-one	464889: Inhibition of MIF	ic50	0.0380	uM
3-(3,4-dihydroxyphenyl)-7-hydroxychromen-4-one	106681: Inhibitory activity against tautomerase macrophage migration inhibitory factor (MIF)	ki	0.0380	uM
4-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-6-yl]oxybutanoic acid	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.0390	uM
2-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-6-yl]oxyacetic acid	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.0480	uM
(6-phenylpyridazin-3-yl) thiophene-2-carboxylate	513953: Inhibition of human MIF tautomerase activity	ic50	0.0500	uM
7-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-N-[4-(7-hydroxy-2-oxo-4H-1,3-benzoxazin-3-yl)phenyl]heptanamide	2115088: Binding affinity to MIF in human A549 cells assessed as inhibition constant	ki	0.0510	uM
6-[morpholin-4-yl-[4-(trifluoromethyl)phenyl]methyl]-1,3-benzodioxol-5-ol	1298946: Covalent inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli using 4-hydroxyphenyl pyruvic acid as substrate assessed as borate-enol complex formation incubated for 30 mins followed substrate addition by microplate reader	ki	0.0520	uM
N-[4-(7-hydroxy-2-oxo-4H-1,3-benzoxazin-3-yl)phenyl]-8-[[2-(1-methyl-2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]octanamide	2115088: Binding affinity to MIF in human A549 cells assessed as inhibition constant	ki	0.0550	uM
4-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-N-[4-(7-hydroxy-2-oxo-4H-1,3-benzoxazin-3-yl)phenyl]butanamide	2115088: Binding affinity to MIF in human A549 cells assessed as inhibition constant	ki	0.0550	uM
N-[5-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-yl)carbamothioylamino]pentyl]-4-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]quinolin-6-yl]oxybutanamide	1384612: Inhibition of recombinant human MIF expressed in Escherichia coli using HPP as substrate preincubated for 30 mins followed by substrate addition	ki	0.0560	uM
10-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-N-[4-(7-hydroxy-2-oxo-4H-1,3-benzoxazin-3-yl)phenyl]decanamide	2115088: Binding affinity to MIF in human A549 cells assessed as inhibition constant	ki	0.0650	uM
5-(5-fluoro-1H-pyrazol-4-yl)-2-[3-[4-(3-morpholin-4-ylpropoxy)phenyl]phenoxy]benzoic acid	1384624: Inhibition of recombinant human MIF expressed in Escherichia coli using HPP as substrate preincubated for 20 mins followed by substrate addition measured for 175 secs	ki	0.0670	uM
8-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-N-[4-(7-hydroxy-2-oxo-4H-1,3-benzoxazin-3-yl)phenyl]octanamide	2115088: Binding affinity to MIF in human A549 cells assessed as inhibition constant	ki	0.0710	uM
2-pyridin-2-yl-1,3-benzothiazin-4-one	2194556: Inhibition of [3H]-BTZO-1 binding to recombinant human C-terminal His-tagged MIF expressed in Escherichia coli BL21 (DE3) measured after 3 hrs by SPA	ic50	0.0710	uM
2-fluoro-4-[4-[6-[2-(2-morpholin-4-ylethoxy)ethoxy]quinolin-2-yl]triazol-1-yl]phenol	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.0740	uM
2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]-7-methyl-1,7-naphthyridin-8-one	1504968: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as decrease in formation of borate complex of enol product using 4-HPP as substrate incubated for 30 mins followed by substrate addition measured for 175 secs	ki	0.0750	uM
butyl 1,3-benzoxazol-2-ylsulfanylformate	513953: Inhibition of human MIF tautomerase activity	ic50	0.0800	uM
3-[(3-hydroxyphenyl)methyl]-5-methoxy-1,3-benzoxazol-2-one	516522: Inhibition of human recombinant biotinylated MIF/CD74 interaction after 30 mins	ic50	0.0800	uM
5-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-N-[4-(7-hydroxy-2-oxo-4H-1,3-benzoxazin-3-yl)phenyl]pentanamide	2115088: Binding affinity to MIF in human A549 cells assessed as inhibition constant	ki	0.0860	uM
2-[2-[1-(3-fluoro-4-hydroxyphenyl)triazol-4-yl]-8-oxo-1,7-naphthyridin-7-yl]acetic acid	1504968: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as decrease in formation of borate complex of enol product using 4-HPP as substrate incubated for 30 mins followed by substrate addition measured for 175 secs	ki	0.0900	uM
3-[(2-methoxyphenyl)methyl]-5-methyl-1,3-benzoxazol-2-one	516522: Inhibition of human recombinant biotinylated MIF/CD74 interaction after 30 mins	ic50	0.0900	uM
3-[(3-hydroxyphenyl)methyl]-5-methyl-1,3-benzoxazole-2-thione	1490032: Inhibition of recombinant human MIF tautomerase activity using 4-HPP as substrate preincubated for 15 mins followed by substrate addition measured after 360 secs	ki	0.1000	uM
3-(3,4-dimethoxyphenyl)-7-hydroxy-4H-1,3-benzoxazin-2-one	1697390: Inhibition of C-terminal His-tagged recombinant human MIF expressed in Escherichia coli BL21 (DE3) using 4-HPP as substrate preincubated for 10 mins followed by substrate addition by UV absorption spectrum analysis	ki	0.1000	uM
4-imidazo[1,2-a]pyridin-3-ylbenzene-1,2-diol	1298951: Inhibition of MIF (unknown origin) tautomerase activity using dopachrome as substrate	ic50	0.1100	uM
3-[(3-methoxyphenyl)methyl]-5,6-dimethyl-1,3-benzoxazol-2-one	516522: Inhibition of human recombinant biotinylated MIF/CD74 interaction after 30 mins	ic50	0.1150	uM
2-fluoro-4-[(E)-[(4-methoxyphenyl)hydrazinylidene]methyl]phenol	281494: Inhibition of MIF tautomerase activity by spectrophotometric assay	ic50	0.1300	uM
4-[4-[6-[2-(2-aminoethoxy)ethoxy]quinolin-2-yl]triazol-1-yl]-2-fluorophenol;2,2,2-trifluoroacetic acid	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.1440	uM
4-[4-[6-[2-(2-methoxyethoxy)ethoxy]quinolin-2-yl]triazol-1-yl]phenol	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.1470	uM
4-[4-[6-[2-(2-morpholin-4-ylethoxy)ethoxy]quinolin-2-yl]triazol-1-yl]phenol	1504968: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as decrease in formation of borate complex of enol product using 4-HPP as substrate incubated for 30 mins followed by substrate addition measured for 175 secs	ki	0.1600	uM
N-(2-aminophenyl)-4-[[2-[4-(7-hydroxy-2-oxo-4H-1,3-benzoxazin-3-yl)phenyl]acetyl]amino]benzamide	2136674: Inhibition of MIF (unknown origin) tautomerase activity incubated for 10 mins by microplate reader analysis	ic50	0.1800	uM
(4,8-dioxo-3-oxa-9-azatetracyclo[7.6.1.02,7.012,16]hexadeca-1(15),2(7),5,12(16),13-pentaen-6-yl) 4-fluorobenzoate	1799792: Tautomerase Enzyme Assay from Article 10.1074/jbc.M110.113951: “Identification and characterization of novel classes of macrophage migration inhibitory factor (MIF) inhibitors with distinct mechanisms of action.”	ki	0.1900	uM
2-[2-[1-(4-hydroxyphenyl)triazol-4-yl]quinolin-6-yl]oxyacetic acid	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.2000	uM
4-[4-[6-(2-methoxyethoxy)quinolin-2-yl]triazol-1-yl]phenol	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.2000	uM
2-[1-(4-hydroxyphenyl)triazol-4-yl]-7-methyl-1,7-naphthyridin-8-one	1504970: Inhibition of recombinant human MIF tautomerase activity assessed as decrease in formation of borate complex of enol product using 4-HPP as substrate incubated for 20 mins by fluorescence polarization method	kd	0.2130	uM
2-chloro-4-[(E)-[(4-methoxyphenyl)hydrazinylidene]methyl]phenol	281494: Inhibition of MIF tautomerase activity by spectrophotometric assay	ic50	0.2200	uM
(2-oxo-1-phenylquinolin-4-yl) benzoate	1799792: Tautomerase Enzyme Assay from Article 10.1074/jbc.M110.113951: “Identification and characterization of novel classes of macrophage migration inhibitory factor (MIF) inhibitors with distinct mechanisms of action.”	ki	0.2300	uM
4-(4-quinolin-2-yltriazol-1-yl)phenol	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.2300	uM
3-isothiocyanatoprop-1-ene	1198788: Inhibition of macrophage migration inhibitory factor tautomerase activity in human Jurkat T cells using L-dopachrome methyl ester as substrate incubated for 30 mins prior to substrate addition measured for 2 mins by spectrophotometric analysis	ic50	0.2500	uM
4-[4-[6-(2-aminoethoxy)quinolin-2-yl]triazol-1-yl]phenol;2,2,2-trifluoroacetic acid	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.2600	uM
4-[4-[6-(oxan-2-ylmethoxy)quinolin-2-yl]triazol-1-yl]phenol	1331426: Inhibition of recombinant human MIF tautomerase activity expressed in Escherichia coli assessed as borate-enol complex formation using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 20 mins followed by substrate addition measured for 175 sec by fluorescence based analysis	ki	0.2700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, increases secretion, decreases reaction, increases abundance, affects expression (+1 more)	6
Particulate Matter	increases reaction, increases expression, decreases expression, increases abundance, affects expression	4
Arsenic Trioxide	affects binding, decreases reaction, decreases expression	3
sodium arsenite	increases abundance, increases expression	2
rottlerin	decreases reaction, increases expression	2
monomethylarsonous acid	increases expression	2
Air Pollutants	increases expression, decreases expression, increases abundance	2
Arsenic	affects expression, increases abundance, increases expression	2
Vehicle Emissions	increases expression, affects expression, increases reaction	2
Lipopolysaccharides	affects cotreatment, decreases expression, decreases reaction, increases expression	2
Mustard Gas	decreases expression, increases secretion	2
Oxygen	increases expression	2
Polystyrenes	decreases expression, increases abundance	2
Tetradecanoylphorbol Acetate	decreases reaction, affects cotreatment, decreases expression, affects binding	2
aristolochic acid I	increases expression	1
ginger extract	decreases reaction, increases abundance, increases expression	1
tungsten carbide	increases expression, affects cotreatment	1
tetrachloroisophthalonitrile	decreases expression	1
sodium arsenate	decreases expression	1
titanium dioxide	increases secretion, affects binding	1
trichostatin A	increases expression	1
arsenite	affects binding, increases reaction	1
zinc chloride	decreases expression	1
cobaltous chloride	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
1,10-phenanthroline	increases expression	1
butylidenephthalide	increases expression	1
cobalt sulfate	increases expression	1
cadmium acetate	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1

ChEMBL screening assays

205 unique, capped per target: 202 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1010227	Binding	Activity of human recombinant MIF tautomerase by LB plot in presence of 3 uM ZINC00806272	Discovery of human macrophage migration inhibitory factor (MIF)-CD74 antagonists via virtual screening. — *J Med Chem*
CHEMBL1291797	Functional	Agonist activity at human MIF tautomerase using 4-hydroxyphenylpyruvate as substrate at 100 uM	Receptor agonists of macrophage migration inhibitory factor. — *Bioorg Med Chem Lett*

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D2BY	Abcam HCT 116 MIF KO	Cancer cell line	Male
CVCL_SY37	HAP1 MIF (-) 1	Cancer cell line	Male
CVCL_T386	Psi-CRIP-MFGhMIF	Transformed cell line	Male
CVCL_XQ55	HAP1 MIF (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00157690	Phase 4	COMPLETED	Study of Alendronate to Prevent and Treat Osteoporosis in Cystic Fibrosis Patients
NCT00208078	Phase 4	TERMINATED	Effect of Non-Invasive Ventilation in Cystic Fibrosis Patient With Chronic Respiratory Failure.
NCT00244270	Phase 4	COMPLETED	Cystic Fibrosis and Totally Implantable Vascular Access Devices
NCT00333385	Phase 4	TERMINATED	Continuous Versus Short Infusions of Ceftazidime in Cystic Fibrosis
NCT00411736	Phase 4	COMPLETED	Scandinavian Cystic Fibrosis Azithromycin Study
NCT00418470	Phase 4	TERMINATED	Prolonging the Duration of Peripheral Venous Catheters in Cystic Fibrosis People
NCT00431964	Phase 4	COMPLETED	Effect of Azithromycin on Lung Function in 6-18 Year-olds With Cystic Fibrosis (CF) Not Infected With P. Aeruginosa
NCT00434278	Phase 4	TERMINATED	A Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease (TOPIC)
NCT00483769	Phase 4	COMPLETED	One Year Glargine Treatment in CFRD Children and Adolescents
NCT00528190	Phase 4	COMPLETED	Treatment of Aspergillus Fumigatus (a Fungal Infection) in Patients With Cystic Fibrosis
NCT00557089	Phase 4	COMPLETED	The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
NCT00572975	Phase 4	COMPLETED	Malabsorption Blood Test:Toward a Novel Approach to Quantify Steatorrhea
NCT00680316	Phase 4	TERMINATED	A Study of Pulmozyme® (Dornase Alpha) in 3- to 5-Year-Old Patients With Cystic Fibrosis
NCT00685035	Phase 4	COMPLETED	Comparison of Airway Clearance Therapy in Cystic Fibrosis Using the Same VEST Therapy Device But With Different Settings
NCT00744250	Phase 4	TERMINATED	Intraduodenal Aspiration Study to Assess the Bioavailability of Oral Pancrecarb® Compared to Placebo Control
NCT00787917	Phase 4	TERMINATED	An Exploratory Study to Assess Multiple Doses of Omalizumab in Patients With Cystic Fibrosis Complicated by Acute Bronchopulmonary Aspergillosis (ABPA)
NCT00843817	Phase 4	COMPLETED	RhDNase and Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum
NCT00890370	Phase 4	COMPLETED	Should Any One Airway Clearance Technique be Recommended for People With Cystic Fibrosis?
NCT00996424	Phase 4	TERMINATED	The Effect of Inhaled N-Acetylcysteine Compared to Normal Saline on Sputum Rheology and Lung Function
NCT01044719	Phase 4	UNKNOWN	Duration of Antibiotics in Infective Exacerbations of Cystic Fibrosis
NCT01100606	Phase 4	COMPLETED	A Study to Evaluate the Mode of Administration and Safety of EUR-1008 (APT-1008) in Infants 1 to 12 Months of Age
NCT01131507	Phase 4	COMPLETED	PR-018: An Open-Label, Safety Extension of Study PR-011
NCT01207245	Phase 4	COMPLETED	Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis
NCT01323101	Phase 4	COMPLETED	Doxycycline Effects on Inflammation in Cystic Fibrosis
NCT01327703	Phase 4	COMPLETED	Control of Steatorrhea in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
NCT01377792	Phase 4	COMPLETED	Study of Long-term Treatment With Hypertonic Saline in Patients With Cystic Fibrosis
NCT01400750	Phase 4	COMPLETED	Comparison of 2 Treatment Regimens for Eradication of P Aeruginosa Infection in Children With Cystic Fibrosis
NCT01429259	Phase 4	COMPLETED	Population Pharmacokinetics of Prolonged Infusion Meropenem in Cystic Fibrosis (CF) Children
NCT01608555	Phase 4	COMPLETED	Tobramycin 300 mg Once-a-day (o.d.) Aerosol in Adults With Cystic Fibrosis
NCT01667094	Phase 4	UNKNOWN	A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis
NCT01694069	Phase 4	TERMINATED	Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis
NCT01702415	Phase 4	WITHDRAWN	Zoledronic Acid in Cystic Fibrosis
NCT01712334	Phase 4	COMPLETED	A Study of the Comparable Efficacy and Safety of Pulmozyme (Dornase Alfa) Delivered by the eRapid Nebulizer System in Patients With Cystic Fibrosis
NCT01737983	Phase 4	COMPLETED	Effect of Lactobacillus Reuteri in Cystic Fibrosis
NCT01844778	Phase 4	COMPLETED	Ease of Use and Microbial Contamination of Tobramycin Inhalation Powder (TIP) Versus Nebulised Tobramycin Inhalation Solution (TIS) and Nebulised Colistimethate (COLI)
NCT01880346	Phase 4	COMPLETED	Comparison of Absorption of Vitamin D in Cystic Fibrosis
NCT01882400	Phase 4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT01937325	Phase 4	UNKNOWN	CPET in CF Patients With One G551D Mutation Taking VX770
NCT02015663	Phase 4	TERMINATED	Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles
NCT02048592	Phase 4	UNKNOWN	Impact of Immunonutrition on the Patients With Cystic Fibrosis
NCT02178540	Phase 4	COMPLETED	Study to Validate the Instructions for Use of TOBI® Podhaler™ in Cystic Fibrosis Patients
NCT02277626	Phase 4	COMPLETED	Electro Flo 5000 and Vest Therapy
NCT02421120	Phase 4	COMPLETED	Population Pharmacokinetics and Safety of Intravenous Ceftolozane/Tazobactam in Adult Cystic Fibrosis Patients
NCT02444234	Phase 4	COMPLETED	Pharmacokinetics of Tedizolid Phosphate in Cystic Fibrosis
NCT02504827	Phase 4	COMPLETED	Steady-state Pharmacokinetics of Ceftazidime/Avibactam in Cystic Fibrosis
NCT02547116	Phase 4	WITHDRAWN	Epidemiology and Treatment of Small-colony Variant Staphylococcus Aureus in Cystic Fibrosis
NCT02677701	Phase 4	COMPLETED	Testing the Effect of Adding Chronic Oral Azithromycin to Inhaled Tobramycin in People With Cystic Fibrosis (CF)
NCT02700282	Phase 4	COMPLETED	Backpack Carrying in Children With Cystic Fibrosis
NCT02823470	Phase 4	TERMINATED	A Pilot Study to Evaluate the Use of Smart Adherence Technology to Measure Lumacaftor/Ivacaftor Adherence in CF Subjects Homozygous for the F508del CFTR Mutation
NCT02823964	Phase 4	COMPLETED	EASY: Extended Access to Sollpura Over Years
NCT02875366	Phase 4	COMPLETED	A Study of the Effects of Lumacaftor/Ivacaftor (LUM/IVA) on Exercise Tolerance in Subjects With Cystic Fibrosis (CF), Homozygous for the F508del-CFTR Mutation
NCT02894684	Phase 4	COMPLETED	Aztreonam for Inhalation Solution (AZLI) for the Treatment of Exacerbations of Cystic Fibrosis
NCT02918409	Phase 4	COMPLETED	IV Colistin for Pulmonary Exacerbations: Improving Safety and Efficacy
NCT03045198	Phase 4	UNKNOWN	Effect of Azithromycin on Fatty Acids in CF
NCT03172793	Phase 4	COMPLETED	Telavancin Pharmacokinetics in Cystic Fibrosis Patients
NCT03256799	Phase 4	COMPLETED	Evaluation of Ivacaftor in Patients Using Ataluren for Nonsense Mutations
NCT03256968	Phase 4	COMPLETED	PTC Study to Evaluate Ataluren in Combination With Ivacaftor
NCT03502070	Phase 4	COMPLETED	Human Factors Study to Validate the User Interface of TOBI Podhaler Using Placebo Capsules
NCT03624101	Phase 4	TERMINATED	Novel Therapeutic Approaches for Treatment of CF Patients With W1282X Premature Termination Codon Mutations
NCT03632525	Phase 4	COMPLETED	Intravenous Iron in Adults With Cystic Fibrosis

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MIF across ~30M SureChEMBL compounds — explore on Sugi Predict.