FHIT

Summary

FHIT (fragile histidine triad diadenosine triphosphatase, HGNC:3701) is a protein-coding gene on chromosome 3p14.2, encoding Bis(5’-adenosyl)-triphosphatase (P49789). Possesses dinucleoside triphosphate hydrolase activity.

The protein encoded by this gene is a P1-P3-bis(5’-adenosyl) triphosphate hydrolase involved in purine metabolism. This gene encompasses the common fragile site FRA3B on chromosome 3, where carcinogen-induced damage can lead to translocations and aberrant transcripts. In fact, aberrant transcripts from this gene have been found in about half of all esophageal, stomach, and colon carcinomas. The encoded protein is also a tumor suppressor, as loss of its activity results in replication stress and DNA damage.

Source: NCBI Gene 2272 — RefSeq curated summary.

At a glance

• GWAS associations: 85
• Clinical variants (ClinVar): 86 total — 1 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 2
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_002012

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3701
Approved symbol	FHIT
Name	fragile histidine triad diadenosine triphosphatase
Location	3p14.2
Locus type	gene with protein product
Status	Approved
Aliases	FRA3B, AP3Aase
Ensembl gene	ENSG00000189283
Ensembl biotype	protein_coding
OMIM	601153
Entrez	2272

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000465330, ENST00000466788, ENST00000468189, ENST00000476844, ENST00000488467, ENST00000490952, ENST00000492590

RefSeq mRNA: 6 — MANE Select: NM_002012 NM_001166243, NM_001320899, NM_001320900, NM_001354589, NM_001354590, NM_002012

CCDS: CCDS2894

Canonical transcript exons

ENST00000492590 — 10 exons

Exon	Start	End
ENSE00001366136	60014007	60014152
ENSE00001820371	61200617	61200665
ENSE00001834327	61251301	61251452
ENSE00001852851	61042047	61042099
ENSE00001861236	59752221	59752321
ENSE00001865208	60821919	60822011
ENSE00001936297	60536860	60536979
ENSE00001955240	59747277	59749579
ENSE00003664016	60011371	60011400
ENSE00003667944	59922346	59922414

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 89.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.8524 / max 543.9886, expressed in 1500 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42787	7.8983	1496
42778	1.2726	86
42779	0.5739	73
42780	0.1077	47

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	89.51	gold quality
right adrenal gland cortex	UBERON:0035827	89.39	gold quality
left adrenal gland cortex	UBERON:0035825	88.76	gold quality
left adrenal gland	UBERON:0001234	88.68	gold quality
apex of heart	UBERON:0002098	88.09	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.60	gold quality
adrenal gland	UBERON:0002369	86.28	gold quality
adrenal cortex	UBERON:0001235	85.81	gold quality
gall bladder	UBERON:0002110	85.06	gold quality
oocyte	CL:0000023	84.74	gold quality
adrenal tissue	UBERON:0018303	84.63	gold quality
right atrium auricular region	UBERON:0006631	83.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.38	gold quality
adult mammalian kidney	UBERON:0000082	83.34	gold quality
heart left ventricle	UBERON:0002084	83.02	gold quality
mucosa of stomach	UBERON:0001199	82.97	gold quality
body of pancreas	UBERON:0001150	82.81	gold quality
cardiac ventricle	UBERON:0002082	82.34	gold quality
spinal cord	UBERON:0002240	82.27	gold quality
cingulate cortex	UBERON:0003027	82.00	gold quality
left lobe of thyroid gland	UBERON:0001120	81.87	gold quality
anterior cingulate cortex	UBERON:0009835	81.85	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.45	gold quality
caudate nucleus	UBERON:0001873	81.41	gold quality
right frontal lobe	UBERON:0002810	81.39	gold quality
pancreatic ductal cell	CL:0002079	81.33	silver quality
metanephros cortex	UBERON:0010533	81.12	gold quality
cardiac atrium	UBERON:0002081	81.00	gold quality
right lobe of thyroid gland	UBERON:0001119	80.72	gold quality
thyroid gland	UBERON:0002046	80.66	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	44.25
E-HCAD-6	yes	41.54
E-GEOD-135922	yes	18.52
E-MTAB-9067	yes	15.72
E-HCAD-35	yes	11.36
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
AXIN2	Repression
BIRC5	Repression
MMP14	Repression

Upstream regulators (CollecTRI, top): DNMT1, E2F1, FOS, KLF6, MYC, TFAP2A, TP53

miRNA regulators (miRDB)

82 targeting FHIT, 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-340-5P	100.00	72.50	4437
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• allelic loss of the FHIT gene may be involved in carcinogenesis in the peripheral lung of patients with IPF. (PMID:11731438)
• reduced Fhit protein expression and loss of heterozygosity at FHIT gene in tumours from smoking and asbestos-exposed lung cancer patients (PMID:11788890)
• Alterations of the fragile histidine triad gene, FHIT, and its encoded products contribute to testicular germ cell tumorigenesis. (PMID:11809703)
• Restoration of fragile histidine triad (FHIT) expression induces apoptosis and suppresses tumorigenicity in lung and cervical cancer cell lines (PMID:11891319)
• FHIT is missing in most human cancers, indicating it has a tumor suppressor function. Inactivation of only one allele compromises this function, indicating a “one-hit” mechanism of tumorigenesis is operative. (PMID:11902576)
• Inactivation of the FHIT gene is an early event in carcinogenesis of the endometrium. (PMID:11915181)
• Exposure to tobacco carcinogens increases the potential for chromosome breakage at fragile site FRA3B. (PMID:12007194)
• The result of this study suggests that FHIT gene may be a tumor suppressor gene in human lung cancer cells. (PMID:12048684)
• FHIT gene is one of the chromosome 3p putative tumor suppressor genes involved in the pathogenesis of this highly malignant neoplasm, gallbladder carcinoma (PMID:12057912)
• Identification of unstable sequences within the common fragile site at 3p14.2: implications for the mechanism of deletions within fragile histidine triad gene/common fragile site at 3p14.2 in tumors. (PMID:12067991)
• FHIT loss played a role in 23% ofexamined colorectal tumors, mostly poorly differentiated carcinomas. It positively correlated with the rate of distant metastases and bad prognosis. Excess FHIT was directly proportional to the apoptotic rate. (PMID:12090476)
• MYCL1, FHIT, SPARC, p16(INK4) and TP53 genes associated to lung cancer in idiopathic pulmoary fibrosis (PMID:12169206)
• reduced Fragile histidine triad expression was significantly associated with absence of mismatch repair protein expression in the advanced colorectal carcinomas ( (PMID:12177781)
• Biallelic FHIT inactivation by LOH & hypermethylation leads to its complete inactivation in breast cancer. Silencing by promoter hypermethylation occurs in primary breast carcinomas, especially those with LOH. FHIT may cause sporadic breast tumorigenesis. (PMID:12231533)
• The breakpoint t(3;20)(p14;p11) targets the potential tumor-suppressor gene FHIT in the FRA3B region and is accompanied by homozygous deletion of exon 5 of the gene and absence of functional FHIT and fusion transcripts. (PMID:12353263)
• Abnormal FHIT gene transcript in breast cancer (PMID:12362975)
• It is suggested that decreased FHIT expression plays an important role in the development and progression of the tumor, and thus may become a new prognostic marker in colorectal carcinoma. (PMID:12419158)
• expression of Fhit is associated with invasion and metastasis of tumor in breast cancer (PMID:12452072)
• evidence that instability extends further than previously reported and extends over 4 megabases (PMID:12483524)
• Loss of Msh2 is not associated with FHIT deletion in breast carcinomas. (PMID:12529969)
• FHIT tumor suppressor gene is down regulated in prostate carcinoma and may be a potential target for therapeutic intervention (PMID:12627509)
• results indicated that the disruption of the mismatch repair system of Msh2 does not mainly lead to allelic loss of the FHIT/FRA3B locus as well as microsatellite instability in esophageal cancer (PMID:12697969)
• High incidence of abnormal Fhit expression in younger patients and presence of human papillomavirus are key players in cervical carcinogenesis (PMID:12698186)
• FHIT inactivation seems to be both an early and a later event, associated with carcinogenesis and progression to more aggressive hepatocellular carcinomas. (PMID:12800227)
• Promoter hypermethylation of this gene is demonstrated in esophageal squamous cell carcinoma. (PMID:12839965)
• exogenous expression of FHIT in Panc-1 cells affects genes regulating cell cycle arrest and apoptosis, and these molecular changes may contribute to the tumor suppressor activity of the FHIT gene (PMID:12890991)
• Fhit protein is associated with highly aggressive phenotypes of cervical carcinoma. (PMID:12893195)
• The loss of Fhit protein expression may be associated with aggressive phenotype of endometrial carcinomas. (PMID:12926121)
• Fhit protein has a role in development of colorectal neoplasm (PMID:12964015)
• Reduced fragile histidine triad gene expression might be involved in the development of gallbladder carcinoma and be correlated with Mlh1 expression (PMID:12969785)
• FHIT is an independent prognostic factor that distinguishes a subgroup of patients with breast cancer who could benefit from adjuvant treatment. (PMID:14566838)
• present data indicate a frequent decrease of Fhit protein expression, thus supporting the significance of FHIT inactivation in development of malignant mesothelioma (PMID:14569398)
• Human and mouse orthologous genes, FHIT and Fhit, are more highly conserved through evolution than PTPRG/Ptprg and yet contain more sequence elements that are exquisitely sensitive to genomic rearrangements (PMID:14630947)
• 5’-CpG island methylation plays an important role in inactivation of the FHIT gene in cervical cancer (PMID:14660280)
• Abnormal FHIT mRNA expression is noted frequently in NHL cell lines and a certain proportion of NHL patients, and decreased FHIT protein expression indicates a significantly worse prognosis in diffuse large B-cell lymphoma. (PMID:14719066)
• p16INK4a and Fhit expression is altered in carcinogenesis and progression of human oral cancer (PMID:14719099)
• reduced Fhit expression occurs in the early stage of gastric carcinogenesis and could be correlated with a lack of Mlh1 expression and gastric phenotype (PMID:14760383)
• The study suggests that mitochondria are involved in the apoptotic activity of FHIT. (PMID:14991669)
• Hypermethylation of the 5’ CpG island of the FHIT gene is associated with hyperdiploid and translocation-negative subtypes of pediatric leukemia (PMID:15026336)
• The data suggest that E2F-1 overexpression plays a role in suppression of tumor, at least in part trough transcriptional regulation of FHIT and relevant activation of WWOX. (PMID:15044096)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fhit	ENSDARG00000078195
mus_musculus	Fhit	ENSMUSG00000060579
rattus_norvegicus	Fhit	ENSRNOG00000064939

Paralogs (2): HINT2 (ENSG00000137133), HINT1 (ENSG00000169567)

Protein

Protein identifiers

Bis(5’-adenosyl)-triphosphatase — P49789 (reviewed: P49789)

Alternative names: AP3A hydrolase, Adenosine 5’-monophosphoramidase FHIT, Adenylylsulfatase, Adenylylsulfate-ammonia adenylyltransferase, Diadenosine 5’,5’’’-P1,P3-triphosphate hydrolase, Dinucleosidetriphosphatase, Fragile histidine triad protein

All UniProt accessions (2): E9PBZ0, P49789

UniProt curated annotations — full annotation on UniProt →

Function. Possesses dinucleoside triphosphate hydrolase activity. Cleaves P(1)-P(3)-bis(5’-adenosyl) triphosphate (Ap3A) to yield AMP and ADP. Can also hydrolyze P(1)-P(4)-bis(5’-adenosyl) tetraphosphate (Ap4A), but has extremely low activity with ATP. Exhibits adenylylsulfatase activity, hydrolyzing adenosine 5’-phosphosulfate to yield AMP and sulfate. Exhibits adenosine 5’-monophosphoramidase activity, hydrolyzing purine nucleotide phosphoramidates with a single phosphate group such as adenosine 5’monophosphoramidate (AMP-NH2) to yield AMP and NH2. Exhibits adenylylsulfate-ammonia adenylyltransferase, catalyzing the ammonolysis of adenosine 5’-phosphosulfate resulting in the formation of adenosine 5’-phosphoramidate. Also catalyzes the ammonolysis of adenosine 5-phosphorofluoridate and diadenosine triphosphate. Modulates transcriptional activation by CTNNB1 and thereby contributes to regulate the expression of genes essential for cell proliferation and survival, such as CCND1 and BIRC5. Plays a role in the induction of apoptosis via SRC and AKT1 signaling pathways. Inhibits MDM2-mediated proteasomal degradation of p53/TP53 and thereby plays a role in p53/TP53-mediated apoptosis. Induction of apoptosis depends on the ability of FHIT to bind P(1)-P(3)-bis(5’-adenosyl) triphosphate or related compounds, but does not require its catalytic activity, it may in part come from the mitochondrial form, which sensitizes the low-affinity Ca(2+) transporters, enhancing mitochondrial calcium uptake. Functions as a tumor suppressor.

Subunit / interactions. Homodimer. Interacts with UBE2I. Interacts with MDM2. Interacts with CTNNB1. Identified in a complex with CTNNB1 and LEF1.

Subcellular location. Cytoplasm. Mitochondrion. Nucleus.

Tissue specificity. Low levels expressed in all tissues tested. Phospho-FHIT observed in liver and kidney, but not in brain and lung. Phospho-FHIT undetected in all tested human tumor cell lines.

Post-translational modifications. Phosphorylation at Tyr-114 by SRC is required for induction of apoptosis.

Disease relevance. A chromosomal aberration involving FHIT has been found in a lymphoblastoid cell line established from a family with renal cell carcinoma and thyroid carcinoma. Translocation t(3;8)(p14.2;q24.1) with RNF139. Although the 3p14.2 breakpoint has been shown to interrupt FHIT in its 5-prime non-coding region, it is unlikely that FHIT is causally related to renal or other malignancies. Associated with digestive tract cancers. Numerous tumor types are found to have aberrant forms of FHIT protein due to deletions in a coding region of chromosome 3p14.2 including the fragile site locus FRA3B.

RefSeq proteins (6): NP_001159715, NP_001307828, NP_001307829, NP_001341518, NP_001341519, NP_002003* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011146	HIT-like	Domain
IPR019808	Histidine_triad_CS	Conserved_site
IPR036265	HIT-like_sf	Homologous_superfamily
IPR039383	FHIT	Family
IPR052677	Dinucleoside_ppp_hydrolase	Family

Pfam: PF01230

Enzyme classification (BRENDA):

• EC 3.6.1.29 — bis(5’-adenosyl)-triphosphatase (BRENDA: 9 organisms, 107 substrates, 29 inhibitors, 39 Km, 14 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
P1-P3-BIS(5’-ADENOSYL) TRIPHOSPHATE	0.001–0.015	10
AP4A	0.0006–0.417	5
P1,P3-BIS(5’-ADENOSYL)TRIPHOSPHATE	0.0007–0.0016	4
5’-O-[AMINO(HYDROXY)PHOSPHORYL]ADENOSINE	0.003–0.015	3
P1-P3-BIS(5’-GUANOSYL) TRIPHOSPHATE	0.002–0.04	3
ADENOSINE-5’-PHOSPHO-N-METHYLIMIDAZOLIDE	0.0053–0.18	2
ADENOSINE-5’-PHOSPHOIMIDAZOLIDE	0.0062–0.026	2
P1-5’-O-ADENOSINE-P3-5’-O-ADENOSINE TRIPHOSPHATE	0.0029–0.026	2
ADENOSINE 5’-PHOSPHORAMIDATE	0.003	1
AP5A	0.013	1
APCF2PPA	0.212	1
APCH2PPA	0.117	1
APCHFPPA	0.09	1
P1-P3-BIS(5’-URACYL) TRIPHOSPHATE	0.025	1
UDP	20	1

Catalyzed reactions (Rhea), 4 shown:

• P(1),P(3)-bis(5’-adenosyl) triphosphate + H2O = AMP + ADP + 2 H(+) (RHEA:13893)
• adenosine 5’-phosphosulfate + H2O = sulfate + AMP + 2 H(+) (RHEA:17041)
• adenosine 5’-phosphosulfate + NH4(+) = adenosine 5’-phosphoramidate + sulfate + 2 H(+) (RHEA:19197)
• adenosine 5’-phosphoramidate + H2O = NH4(+) + AMP (RHEA:67916)

UniProt features (40 total): mutagenesis site 12, strand 8, helix 6, binding site 5, modified residue 2, chain 1, domain 1, short sequence motif 1, sequence conflict 1, active site 1, turn 1, site 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
1FIT	X-RAY DIFFRACTION	1.85
2FIT	X-RAY DIFFRACTION	1.9
5FIT	X-RAY DIFFRACTION	2.3
7P8P	X-RAY DIFFRACTION	2.34
3FIT	X-RAY DIFFRACTION	2.4
4FIT	X-RAY DIFFRACTION	2.5
2FHI	X-RAY DIFFRACTION	2.6
6FIT	X-RAY DIFFRACTION	2.6
1FHI	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49789-F1	95.15	0.90

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 (2): 96 (tele-amp-histidine intermediate); 114 (important for induction of apoptosis)

Ligand- & substrate-binding residues (5): 8; 27; 83; 89–92; 98

Post-translational modifications (2): 114, 145

Mutagenesis-validated functional residues (12):

Position	Phenotype
10	strongly reduces affinity for substrates and impairs apoptosis; when associated with w-25.
25	reduces affinity for substrates and impairs apoptosis. strongly reduces affinity for substrates and impairs apoptosis; w
35	50% decrease in catalytic activity. no loss in substrate binding.
94	75% decrease in catalytic activity. no loss in substrate binding.
96	loss of catalytic activity.
96	total loss of catalytic activity. rescuable with free imidazole.
96	total loss of catalytic activity. no loss in substrate binding.
98	98% decrease in catalytic activity.
114	impairs induction of apoptosis. strongly reduced affinity for substrates.
114	impairs induction of apoptosis. reduces affinity for substrates.
114	loss of phosphorylation by src. impairs induction of apoptosis.
145	no effect on phosphorylation by src.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 213 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOLDRATH_IMMUNE_MEMORY, MODULE_45, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TAKADA_GASTRIC_CANCER_COPY_NUMBER_DN, MODULE_16, GGAMTNNNNNTCCY_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, CEBPB_01, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, OHM_METHYLATED_IN_ADULT_CANCERS, GOBP_APOPTOTIC_SIGNALING_PATHWAY, LOPES_METHYLATED_IN_COLON_CANCER_DN

GO Biological Process (5): purine nucleotide metabolic process (GO:0006163), diadenosine triphosphate catabolic process (GO:0015964), negative regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032435), intrinsic apoptotic signaling pathway by p53 class mediator (GO:0072332), apoptotic process (GO:0006915)

GO Molecular Function (11): nucleotide binding (GO:0000166), ubiquitin protein ligase binding (GO:0031625), identical protein binding (GO:0042802), adenosine 5’-monophosphoramidase activity (GO:0043530), adenylylsulfate-ammonia adenylyltransferase activity (GO:0047352), adenylylsulfatase activity (GO:0047627), bis(5’-adenosyl)-triphosphatase activity (GO:0047710), catalytic activity (GO:0003824), protein binding (GO:0005515), transferase activity (GO:0016740), hydrolase activity (GO:0016787)

GO Cellular Component (6): fibrillar center (GO:0001650), nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), plasma membrane (GO:0005886)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
catalytic activity	2
intracellular membrane-bounded organelle	2
cytoplasm	2
nucleotide metabolic process	1
purine-containing compound metabolic process	1
diadenosine polyphosphate catabolic process	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
negative regulation of proteasomal protein catabolic process	1
negative regulation of ubiquitin-dependent protein catabolic process	1
signal transduction by p53 class mediator	1
intrinsic apoptotic signaling pathway	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
ubiquitin-like protein ligase binding	1
protein binding	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	1
adenylyltransferase activity	1
hydrolase activity, acting on acid anhydrides, in sulfonyl-containing anhydrides	1
pyrophosphatase activity	1
molecular_function	1
binding	1
nucleolus	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1622 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FHIT	WWOX	Q9NZC7	937
FHIT	FDXR	P22570	864
FHIT	NUDT2	P50583	813
FHIT	CTNNB1	P35222	736
FHIT	HINT1	P49773	734
FHIT	RASSF1	Q9NS23	720
FHIT	CDKN2A	P42771	700
FHIT	PTPRG	P23470	692
FHIT	RARB	P10826	664
FHIT	ZFP37	Q9Y6Q3	661
FHIT	DAPK1	P53355	656
FHIT	APTX	Q7Z2E3	652
FHIT	RNF139	Q8WU17	649
FHIT	F5H6H0	F5H6H0	646
FHIT	TP53	P04637	620

IntAct

35 interactions, top by confidence:

A	B	Type	Score
FHIT	FHIT	psi-mi:“MI:0915”(physical association)	0.950
FHIT	FHIT	psi-mi:“MI:0407”(direct interaction)	0.950
LEF1	CTNNB1	psi-mi:“MI:0914”(association)	0.890
FHIT	CTNNB1	psi-mi:“MI:0915”(physical association)	0.600
FHIT	CTNNB1	psi-mi:“MI:0407”(direct interaction)	0.600
FHIT	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
GAST	ZZEF1	psi-mi:“MI:0914”(association)	0.530
LEF1	FHIT	psi-mi:“MI:0915”(physical association)	0.500
FHIT	MTMR6	psi-mi:“MI:0915”(physical association)	0.400
FHIT	REL	psi-mi:“MI:0915”(physical association)	0.370
FHIT	TRIM23	psi-mi:“MI:0915”(physical association)	0.370
FHIT	RAB40B	psi-mi:“MI:0915”(physical association)	0.370
RABL2A	FHIT	psi-mi:“MI:0914”(association)	0.350
ARHGAP19	FHIT	psi-mi:“MI:0914”(association)	0.350
CBY2	FHIT	psi-mi:“MI:0914”(association)	0.350
FDCSP	FHIT	psi-mi:“MI:0914”(association)	0.350
GGH	MANBA	psi-mi:“MI:0914”(association)	0.350

BioGRID (33): FHIT (Two-hybrid), FHIT (Two-hybrid), FHIT (Synthetic Growth Defect), FHIT (Affinity Capture-MS), MTMR6 (Affinity Capture-MS), FHIT (Affinity Capture-MS), FHIT (Synthetic Lethality), FHIT (Two-hybrid), FHIT (Two-hybrid), FHIT (Two-hybrid), FHIT (Reconstituted Complex), UBE2I (Affinity Capture-Western), UBE2I (Two-hybrid), MTMR6 (Affinity Capture-MS), FHIT (Affinity Capture-MS)

ESM2 similar proteins: A0A0J9UVG7, A0A1D3PCM3, A2QCJ2, A7EUB3, B6Q8T5, C8VP37, E4ZHV7, E9DV56, F4HYF3, F4KEV7, O13492, O47881, O76463, O89106, O94586, P0CQ16, P0CQ17, P31318, P40510, P42856, P49776, P49789, P51659, P51660, P54898, P87228, P97852, Q04344, Q0U796, Q1KZG4, Q2URJ0, Q4IER0, Q4IQC1, Q4WMU1, Q4X0Z7, Q59WG0, Q5AT15, Q5AZT7, Q7S8C4, Q7SHU9

Diamond homologs: A6ZYQ3, B3LFZ1, B5VGI4, C7GQV5, C8Z5L6, F4KEV7, O07513, O76463, O76464, O89106, P49775, P49776, P49789, P95937, P9WMK8, P9WMK9, P9WML0, P9WML1, Q04344, Q1KZG4, Q86KK2, Q9JIX3, P73481, Q58276, Q9Z863, C4LYI2, O31664, O94586, O94660, P0DP64, P0DP66, P0DP67, P0DP68, P26724, P32084, P47016, P47378, P49773, P49954, P55175

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
FHIT	down-regulates	MDM2
FHIT	up-regulates	TP53
FHIT	down-regulates	AKT
FHIT	down-regulates	AKT2
FHIT	down-regulates	AKT3
FHIT	“down-regulates quantity by repression”	AXIN2	“transcriptional regulation”
FHIT	“down-regulates quantity by repression”	BIRC5	“transcriptional regulation”
FHIT	down-regulates	CTNNB1	binding
FHIT	“down-regulates quantity by repression”	MMP14	“transcriptional regulation”
FHIT	down-regulates	AKT1
SRC	“up-regulates activity”	FHIT	phosphorylation

Disease & clinical

Cancer significance

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

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	5
Uncertain significance	46
Likely benign	18
Benign	4

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
3779467	NM_002012.4(FHIT):c.280-26365_280-26364del	Pathogenic
545300	NC_000003.12:g.(?60389119)(60571624_?)del	Likely pathogenic
545301	NC_000003.12:g.(?60408194)(60672864_?)del	Likely pathogenic
545302	NC_000003.12:g.(?60438915)(60817364_?)del	Likely pathogenic
545303	NC_000003.12:g.(?60501297)(60591815_?)del	Likely pathogenic
974727	NM_002012.4(FHIT):c.103+32489_103+54184del	Likely pathogenic

SpliceAI

7408 predictions. Top by Δscore:

Variant	Effect	Δscore
3:59752324:T:C	acceptor_gain	1.0000
3:59922423:G:C	acceptor_gain	1.0000
3:59752321:GC:G	acceptor_loss	0.9900
3:59752322:C:A	acceptor_loss	0.9900
3:59752322:C:CC	acceptor_gain	0.9900
3:59752323:T:C	acceptor_gain	0.9900
3:59752324:T:TC	acceptor_gain	0.9900
3:59888061:TTCTA:T	donor_gain	0.9900
3:59922411:CGTG:C	acceptor_gain	0.9900
3:59922415:C:CC	acceptor_gain	0.9900
3:59922423:G:GC	acceptor_gain	0.9900
3:60011367:TCA:T	donor_loss	0.9900
3:60011368:CAC:C	donor_loss	0.9900
3:60011370:C:CT	donor_loss	0.9900
3:60013149:TCATA:T	donor_gain	0.9900
3:60014002:CTCA:C	donor_loss	0.9900
3:60014003:TCAC:T	donor_loss	0.9900
3:60014004:CACCT:C	donor_loss	0.9900
3:60014005:ACC:A	donor_loss	0.9900
3:60014006:CCTG:C	donor_gain	0.9900
3:60014265:C:CC	acceptor_gain	0.9900
3:60122639:AGAG:A	donor_gain	0.9900
3:60272018:A:AC	donor_gain	0.9900
3:60272019:C:CC	donor_gain	0.9900
3:60348242:G:C	donor_gain	0.9900
3:60441010:T:TA	donor_gain	0.9900
3:60447812:AAG:A	donor_gain	0.9900
3:59752215:CTTTA:C	donor_loss	0.9800
3:59752216:TTTA:T	donor_loss	0.9800
3:59752217:TTACC:T	donor_loss	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000004344 (3:60609366 C>A,T), RS1000004594 (3:59764216 T>A,C), RS1000005439 (3:60916601 A>C), RS1000007023 (3:59977877 T>C), RS1000008105 (3:60080106 G>A,C), RS1000009658 (3:60414371 T>A), RS1000016681 (3:60027515 G>A), RS1000017731 (3:60293306 T>C), RS1000018925 (3:61036046 G>A), RS1000019120 (3:60201687 T>C), RS1000021626 (3:59779053 G>A), RS1000021692 (3:60263495 T>C), RS1000022019 (3:60980713 A>G), RS1000023185 (3:60997738 G>A), RS1000025496 (3:60358628 T>C)

Disease associations

OMIM: gene MIM:601153 | disease phenotypes: MIM:114480, MIM:181500, MIM:209850

GenCC curated gene-disease

Mondo (9): primary ovarian failure (MONDO:0005387), familial ovarian cancer (MONDO:0016248), hereditary breast ovarian cancer syndrome (MONDO:0003582), hereditary breast carcinoma (MONDO:0016419), lip and oral cavity carcinoma (MONDO:0023644), schizophrenia (MONDO:0005090), autism (MONDO:0005260), primary amenorrhea (MONDO:1060208), megacolon (MONDO:0001273)

Orphanet (5): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), Hereditary breast cancer (Orphanet:227535), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619), OBSOLETE: Familial ovarian cancer (Orphanet:213517), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0100753	Schizophrenia
HP:0000717	Autism

GWAS associations

85 associations (top):

Study	Trait	p-value
GCST000281_13	Attention deficit hyperactivity disorder	8.000000e-06
GCST000578_5	Major depressive disorder	4.000000e-06
GCST000904_5	Asperger disorder	4.000000e-06
GCST000943_5	Aortic root size	8.000000e-06
GCST001431_1	Adverse response to lamotrigine and phenytoin	7.000000e-07
GCST001442_3	Orofacial clefts	7.000000e-06
GCST001591_10	Response to citalopram treatment	2.000000e-06
GCST001651_36	Response to amphetamines	2.000000e-06
GCST001712_27	Myopia (pathological)	3.000000e-06
GCST002104_5	Bronchopulmonary dysplasia	3.000000e-06
GCST002438_3	Conotruncal heart defects	1.000000e-06
GCST002497_6	Blood pressure	8.000000e-07
GCST002774_9	Cognitive function	6.000000e-06
GCST002783_279	Body mass index	1.000000e-10
GCST002783_41	Body mass index	3.000000e-07
GCST002783_634	Body mass index	2.000000e-10
GCST002783_74	Body mass index	3.000000e-06
GCST003501_1	Asparaginase-induced acute pancreatitis in acute lymphoblastic leukemia (onset time)	8.000000e-06
GCST003992_31	Photic sneeze reflex	2.000000e-36
GCST004024_2	Depressive symptom measurement or major depressive disorder	7.000000e-10
GCST004136_26	Methadone dose in opioid dependence	6.000000e-06
GCST004495_38	BMI (adjusted for smoking behaviour)	2.000000e-10
GCST004495_39	BMI (adjusted for smoking behaviour)	4.000000e-15
GCST004495_40	BMI (adjusted for smoking behaviour)	3.000000e-07
GCST004497_129	Body mass index (joint analysis main effects and smoking interaction)	3.000000e-08
GCST004497_137	Body mass index (joint analysis main effects and smoking interaction)	2.000000e-16
GCST004497_138	Body mass index (joint analysis main effects and smoking interaction)	1.000000e-11
GCST004498_10	BMI in smokers	3.000000e-08
GCST004498_9	BMI in smokers	3.000000e-06
GCST004499_34	BMI in non-smokers	3.000000e-10

EFO canonical traits (28, from GWAS)

EFO ID	Trait name
EFO:0004207	pathological myopia
EFO:0005939	parental genotype effect measurement
EFO:0006335	systolic blood pressure
EFO:0004337	intelligence
EFO:0004340	body mass index
EFO:1001507	asparaginase-induced acute pancreatitis
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome
EFO:0007006	depressive symptom measurement
EFO:0007907	methadone dose measurement
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0006919	cardiovascular event measurement
EFO:0008395	response to darapladib
EFO:0008344	response to placebo
EFO:0003892	pulmonary function measurement
EFO:0008431	maximal voluntary ventilation
EFO:0005116	urinary metabolite measurement
EFO:0009764	eye colour measurement
EFO:0009951	response to surgery
EFO:0009953	post-operative myocardial infarction
EFO:0004338	body weight
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004952	disease recurrence
EFO:0008343	sex interaction measurement
EFO:0004531	urate measurement
EFO:0007701	spine bone mineral density
EFO:0009749	age at first sexual intercourse measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D008531	Megacolon	C06.405.469.158.701
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C562840	Breast Cancer, Familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1795151 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 36,848 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL265502	SURAMIN	3	36,848

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs49411	Efficacy	3	antidepressants	Major Depressive Disorder
rs760316	Efficacy	3	interferon beta-1a;interferon beta-1b	Multiple Sclerosis

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs49411	FHIT	3	0.00	1	antidepressants
rs760316	FHIT	3	2.50	1	interferon beta-1a;interferon beta-1b
rs138741635	FHIT		0.00	0
rs241692	FHIT		0.00	0

Binding affinities (BindingDB)

24 measured of 24 human assays (24 total across all organisms); most potent 24 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
AppppA analog, 6 (X=S)	KI	35 nM
AppppA analog, 12 (X=S)	KI	40 nM
AppppA analog, 13 (X=S)	KI	65 nM
AppppA analog, 15 (X=S)	KI	78 nM
AppppA analog, 17 (X=S)	KI	110 nM
AppppA analog, 5 (X=S)	KI	220 nM
AppppA analog, 9 (X=S)	KI	230 nM
AppppA analog, 17 (X=O)	KI	420 nM
AppppA analog, 14 (X=S)	KI	700 nM
AppppA analog, 14 (X=O)	KI	900 nM
AppppA analog, 5 (X=O)	KI	1500 nM
AppppA analog, 12 (X=O)	KI	1500 nM
AppppA analog, 15 (X=O)	KI	1500 nM
AppppA analog, 1 (X=O)	KI	2600 nM
AppppA analog, 2 (X=S)	KI	2600 nM
AppppA analog, 16 (X=S)	KI	2700 nM
AppppA analog, 8 (X=S)	KI	3000 nM
AppppA analog, 13 (X=O)	KI	3200 nM
AppppA analog, 10 (X=S)	KI	3300 nM
AppppA analog, 6 (X=O)	KI	4700 nM
AppppA analog, 11 (X=S)	KI	5200 nM
AppppA analog, 7 (X=S)	KI	76000 nM
AppppA analog, 3 (X=S)	KI	86000 nM
AppppA analog, 4 (X=S)	KI	86000 nM

ChEMBL bioactivities

25 potent at pChembl≥5 of 31 total, top 25 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.46	Ki	35	nM	CHEMBL1812070
7.46	Ki	35	nM	CHEMBL1812069
7.46	Ki	35	nM	CHEMBL1812068
7.46	Ki	35	nM	CHEMBL1812067
7.46	Ki	35	nM	CHEMBL1812066
7.31	IC50	49	nM	CHEMBL5083166
7.22	IC50	60	nM	CHEMBL5079345
6.92	IC50	120	nM	CHEMBL5079345
6.85	IC50	140	nM	CHEMBL5078809
6.11	IC50	770	nM	CHEMBL5075611
6.00	IC50	1010	nM	CHEMBL5093727
5.80	IC50	1580	nM	CHEMBL5078205
5.72	IC50	1900	nM	CHEMBL5078809
5.55	IC50	2800	nM	CHEMBL5069986
5.46	IC50	3430	nM	CHEMBL5076149
5.43	IC50	3730	nM	CHEMBL5081769
5.40	IC50	4000	nM	CHEMBL5088775
5.40	IC50	3980	nM	CHEMBL5075193
5.37	IC50	4240	nM	CHEMBL5093738
5.33	IC50	4660	nM	CHEMBL1520857
5.30	IC50	5000	nM	CHEMBL1444825
5.28	IC50	5300	nM	CHEMBL5077048
5.26	IC50	5500	nM	CHEMBL5092878
5.09	IC50	8100	nM	CHEMBL5083554
5.06	IC50	8800	nM	CHEMBL5083166

PubChem BioAssay actives

46 with measured affinity, of 119 total; 43 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
(2R,3R,4S,5R)-2-(6-aminopurin-9-yl)-5-[[[3-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-sulfanylphosphoryl]oxy-2-hydroxypropoxy]-hydroxyphosphinothioyl]oxymethyl]oxolane-3,4-diol	612652: Inhibition of Fragile histidine triad protein hydrolytic activity	ki	0.0350	uM
(2R,3R,4S,5R)-2-(6-aminopurin-9-yl)-5-[[[2-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-3-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-sulfanylphosphoryl]oxypropoxy]-hydroxyphosphinothioyl]oxymethyl]oxolane-3,4-diol	612652: Inhibition of Fragile histidine triad protein hydrolytic activity	ki	0.0350	uM
(2R,3R,4S,5R)-2-(6-aminopurin-9-yl)-5-[[[2,2-bis[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxymethyl]-3-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-sulfanylphosphoryl]oxypropoxy]-hydroxyphosphinothioyl]oxymethyl]oxolane-3,4-diol	612652: Inhibition of Fragile histidine triad protein hydrolytic activity	ki	0.0350	uM
(2R,3R,4S,5R)-2-(6-aminopurin-9-yl)-5-[[[2-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxymethyl]-2-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-sulfanylphosphoryl]oxymethyl]-3-dihydroxyphosphinothioyloxypropoxy]-hydroxyphosphinothioyl]oxymethyl]oxolane-3,4-diol	612652: Inhibition of Fragile histidine triad protein hydrolytic activity	ki	0.0350	uM
(2R,3R,4S,5R)-2-(6-aminopurin-9-yl)-5-[[[3-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-sulfanylphosphoryl]oxy-2-dihydroxyphosphinothioyloxypropoxy]-hydroxyphosphinothioyl]oxymethyl]oxolane-3,4-diol	612652: Inhibition of Fragile histidine triad protein hydrolytic activity	ki	0.0350	uM
2-(6-aminopurin-9-yl)-5-[[[3-[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-2-hydroxypropoxy]-oxidophosphinothioyl]oxymethyl]oxolane-3,4-diol	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	0.0350	uM
2-(6-aminopurin-9-yl)-5-[[[2-[[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphinothioyl]oxymethyl]-2-[[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-sulfidophosphoryl]oxymethyl]-3-[hydroxy(oxido)phosphinothioyl]oxypropoxy]-oxidophosphinothioyl]oxymethyl]oxolane-3,4-diol	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	0.0400	uM
10-(4-bromophenyl)-7,7-dimethyl-5,6,8,10-tetrahydroindeno[1,2-b]quinoline-9,11-dione	1810935: Inhibition of human FHIT expressed in Escherichia coli BL21(DE3)-RIL cells using AP3A as substrate pretreated for 10 mins followed by substrate addition and measured after 1 hr by HPLC analysis	ic50	0.0490	uM
2-[(4-bromo-6-oxo-7,8,9,10-tetrahydrobenzo[c]chromen-3-yl)oxy]-N-hydroxyacetamide	1810921: Inhibition of recombinant human FHIT assessed as reduction in AP3Aase activity measured after 45 mins by HPLC analysis	ic50	0.0600	uM
2-(6-aminopurin-9-yl)-5-[[[2,2-bis[[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphinothioyl]oxymethyl]-3-[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-sulfidophosphoryl]oxypropoxy]-oxidophosphinothioyl]oxymethyl]oxolane-3,4-diol	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	0.0650	uM
2-(6-aminopurin-9-yl)-5-[[[2-[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-3-[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-sulfidophosphoryl]oxypropoxy]-oxidophosphinothioyl]oxymethyl]oxolane-3,4-diol	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	0.0780	uM
1,3-bis[[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphinothioyl]oxy]propan-2-yloxy-sulfidophosphinate	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	0.1100	uM
N-hydroxy-2-[(4-methyl-6-oxo-7,8,9,10-tetrahydrobenzo[c]chromen-3-yl)oxy]acetamide	1810921: Inhibition of recombinant human FHIT assessed as reduction in AP3Aase activity measured after 45 mins by HPLC analysis	ic50	0.1400	uM
(2R,3R,4S)-2-(6-aminopurin-9-yl)-5-[[[[[(2R,3S,4R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphinothioyl]oxymethylidene-hydroxy-oxido-lambda5-phosphanyl]methoxy-oxidophosphinothioyl]oxymethyl]oxolane-3,4-diol	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	0.2200	uM
2-(6-aminopurin-9-yl)-5-[[3-[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphinothioyl]oxypropoxy-oxidophosphinothioyl]oxymethyl]oxolane-3,4-diol	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	0.2300	uM
[1-[[(2R,3S,4R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxy-3-[[(3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxypropan-2-yl] phosphate	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	0.4200	uM
[2,2-bis[[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphinothioyl]oxymethyl]-3-dioxidophosphinothioyloxypropoxy]-sulfidophosphinate	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	0.7000	uM
4-[2-[(E)-(1-methyl-2,5-dioxoimidazolidin-4-ylidene)methyl]pyrrol-1-yl]benzoic acid	1810916: Inhibition of recombinant human FHIT incubated for 1hr in presence of tokyogreen-labeled CMP probe by fluorescence based analysis	ic50	0.7700	uM
[2-[[[(2R,3S,4R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxymethyl]-2-[[[(3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxymethyl]-3-phosphonatooxypropyl] phosphate	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	0.9000	uM
diethyl 2-amino-5-methylthiophene-3,4-dicarboxylate	1810916: Inhibition of recombinant human FHIT incubated for 1hr in presence of tokyogreen-labeled CMP probe by fluorescence based analysis	ic50	1.0100	uM
[3-[[(3R,4S)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxy-2-[[[(2R,3S,4R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxymethyl]-2-[[[(3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxymethyl]propyl] hydrogen phosphate	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	1.5000	uM
[1-[[(2R,3S,4R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxy-3-[[(3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxypropan-2-yl] [(2R,3S,4R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	1.5000	uM
[[[(2R,3S,4R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxymethyl-hydroxy-oxido-lambda5-phosphanylidene]methyl [(3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	1.5000	uM
2-(2-pyridin-3-yl-4-pyridinyl)-3H-benzimidazole-5-carboxylic acid	1810916: Inhibition of recombinant human FHIT incubated for 1hr in presence of tokyogreen-labeled CMP probe by fluorescence based analysis	ic50	1.5800	uM
[[(2R,3S,4R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl] [[[(3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxy-oxidophosphoryl] phosphate	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	2.6000	uM
2-(6-aminopurin-9-yl)-5-[[2-[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphinothioyl]oxyethoxy-oxidophosphinothioyl]oxymethyl]oxolane-3,4-diol	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	2.6000	uM
(2R,3R,4S)-2-(6-aminopurin-9-yl)-5-[[[[2-[[(2R,3S,4R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-3-[[[(2R,3S,4R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-sulfidophosphoryl]amino]propyl]amino]-oxidophosphinothioyl]oxymethyl]oxolane-3,4-diol	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	2.7000	uM
N-hydroxy-2-[(4-methoxy-6-oxo-7,8,9,10-tetrahydrobenzo[c]chromen-3-yl)oxy]acetamide	1810916: Inhibition of recombinant human FHIT incubated for 1hr in presence of tokyogreen-labeled CMP probe by fluorescence based analysis	ic50	2.8000	uM
2-[[[2-amino-3-[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphinothioyl]oxypropoxy]-oxidophosphinothioyl]oxymethyl]-5-(6-aminopurin-9-yl)oxolane-3,4-diol	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	3.0000	uM
[3-[[(3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxy-2-[[[(2R,3S,4R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxymethyl]-2-[[[(3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxymethyl]propyl] [(3R,4S)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	3.2000	uM
(3R,4S,5R)-2-(6-aminopurin-9-yl)-5-[[[3-[[[(3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphinothioyl]amino]propylamino]-oxidophosphinothioyl]oxymethyl]oxolane-3,4-diol	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	3.3000	uM
N-(furan-2-ylmethylcarbamoyl)-2-(5-nitro-2-oxo-1-pyridinyl)acetamide	1810916: Inhibition of recombinant human FHIT incubated for 1hr in presence of tokyogreen-labeled CMP probe by fluorescence based analysis	ic50	3.4300	uM
4-[(E)-[(1,5-diphenyl-1,2,4-triazole-3-carbonyl)hydrazinylidene]methyl]benzoic acid	1810916: Inhibition of recombinant human FHIT incubated for 1hr in presence of tokyogreen-labeled CMP probe by fluorescence based analysis	ic50	3.7300	uM
4-hydroxy-6-oxo-1-phenylpyridazine-3-carbohydrazide	1810916: Inhibition of recombinant human FHIT incubated for 1hr in presence of tokyogreen-labeled CMP probe by fluorescence based analysis	ic50	3.9800	uM
2-[(4-bromo-6-oxo-7,8,9,10-tetrahydrobenzo[c]chromen-3-yl)oxy]acetohydrazide	1810916: Inhibition of recombinant human FHIT incubated for 1hr in presence of tokyogreen-labeled CMP probe by fluorescence based analysis	ic50	4.0000	uM
methyl 3-[(2S,5aS,8aR)-6-(2-methoxyacetyl)-1-methyl-5-oxo-3,4,5a,7,8,8a-hexahydro-2H-pyrrolo[3,2-e][1,4]diazepin-2-yl]propanoate	1810916: Inhibition of recombinant human FHIT incubated for 1hr in presence of tokyogreen-labeled CMP probe by fluorescence based analysis	ic50	4.2400	uM
4,9-dimethyl-3-(2H-tetrazol-5-ylmethoxy)-7,8,9,10-tetrahydrobenzo[c]chromen-6-one	1810916: Inhibition of recombinant human FHIT incubated for 1hr in presence of tokyogreen-labeled CMP probe by fluorescence based analysis	ic50	4.6600	uM
[3-[[(2R,3S,4R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxy-2-hydroxypropyl] [(4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	4.7000	uM
4-methyl-3-(2H-tetrazol-5-ylmethoxy)-7,8,9,10-tetrahydrobenzo[c]chromen-6-one	1810916: Inhibition of recombinant human FHIT incubated for 1hr in presence of tokyogreen-labeled CMP probe by fluorescence based analysis	ic50	5.0000	uM
2-(6-aminopurin-9-yl)-5-[[3-[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphinothioyl]sulfanylpropylsulfanyl-oxidophosphinothioyl]oxymethyl]oxolane-3,4-diol	1799560: Enzyme Inhibition Assay from Article 10.1186/1472-6769-1-3: “Di-, tri- and tetra-5’-O-phosphorothioadenosyl substituted polyols as inhibitors of Fhit: Importance of the alpha-beta bridging oxygen and beta phosphorus replacement.”	ki	5.2000	uM
2-[(4-ethyl-6-oxo-7,8,9,10-tetrahydrobenzo[c]chromen-3-yl)oxy]-N-hydroxyacetamide	1810916: Inhibition of recombinant human FHIT incubated for 1hr in presence of tokyogreen-labeled CMP probe by fluorescence based analysis	ic50	5.3000	uM
N-hydroxy-2-[(6-oxo-7,8,9,10-tetrahydrobenzo[c]chromen-3-yl)oxy]acetamide	1810916: Inhibition of recombinant human FHIT incubated for 1hr in presence of tokyogreen-labeled CMP probe by fluorescence based analysis	ic50	5.5000	uM
2-[(4-acetyl-6-oxo-7,8,9,10-tetrahydrobenzo[c]chromen-3-yl)oxy]-N-hydroxyacetamide	1810916: Inhibition of recombinant human FHIT incubated for 1hr in presence of tokyogreen-labeled CMP probe by fluorescence based analysis	ic50	8.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	9
Aflatoxin B1	affects expression, decreases expression, decreases methylation	8
Tobacco Smoke Pollution	affects methylation, increases abundance, increases methylation, decreases expression	3
lasiocarpine	decreases expression	2
methyleugenol	decreases expression	2
Decitabine	affects methylation, affects expression, affects cotreatment, decreases expression, decreases reaction	2
Methapyrilene	affects methylation, increases expression	2
N-Nitrosopyrrolidine	decreases expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
testosterone enanthate	affects expression	1
ponasterone A	affects expression	1
trichostatin A	affects cotreatment, affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
nickel sulfide	decreases expression, increases mutagenesis	1
sodium arsenite	decreases expression, decreases reaction	1
butyraldehyde	decreases expression	1
4-nitroso-N-phenylaniline	affects response to substance	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	decreases methylation	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
U 0126	decreases expression, decreases reaction	1
clothianidin	increases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Sunitinib	increases expression	1
alpha-Chlorohydrin	decreases expression	1

ChEMBL screening assays

21 unique, capped per target: 19 binding, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1817387	Binding	Inhibition of Fragile histidine triad protein hydrolytic activity	Evaluation of influence of Ap4A analogues on Fhit-positive HEK293T cells; cytotoxicity and ability to induce apoptosis. — Bioorg Med Chem
CHEMBL3860849	ADMET	Stability of compound assessed as human Fhit expressed in Escherichia coli BL21-mediated compound initial rate of hydrolysis per microgram of protein at 50 to 200 uM after 5 to 120 mins by RP-HPLC analysis	Phosphorothioate analogs of P1,P3-di(nucleosid-5’-yl) triphosphates: Synthesis, assignment of the absolute configuration at P-atoms and P-stereodependent recognition by Fhit hydrolase. — Bioorg Med Chem

Cellosaurus cell lines

17 cell lines: 17 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0623	MDA-MB-436	Cancer cell line	Female
CVCL_1252	HCC1428	Cancer cell line	Female
CVCL_1255	HCC1569	Cancer cell line	Female
CVCL_1258	HCC1806	Cancer cell line	Female
CVCL_A1FP	HCC1569 GDC-0941_resistant	Cancer cell line	Female
CVCL_C8VV	HCC1806-EGFP	Cancer cell line	Female
CVCL_C9DB	HCC1428/Cas9-hyg	Cancer cell line	Female
CVCL_D7EJ	WHCO1	Cancer cell line	Male
CVCL_D7EL	WHCO5	Cancer cell line	Male
CVCL_D7EM	WHCO6	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT01418118	PHASE4	COMPLETED	Assessment of the Effects of Pressors on Graft Blood Flow After Free Tissue Transfer Surgery
NCT03017053	PHASE4	UNKNOWN	The Optimal Neck Treatments Strategy of Early Oral Cancer Based on Adverse Pathological Factor
NCT03684707	PHASE4	UNKNOWN	Cancer Chemoprevention by Metformin Hydrochloride Compared to Placebo in Oral Potentially Malignant Lesions
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00158652	PHASE3	COMPLETED	Accelerated Radiotherapy and Concomitant Chemo-radiotherapy in HNSCC
NCT00158678	PHASE3	COMPLETED	IMRT Plus Cisplatin Versus Conventional Radiotherapy Plus Cisplatin in Stage III-IV HNSCC
NCT00402779	PHASE3	COMPLETED	Erlotinib Prevention of Oral Cancer (EPOC)
NCT00655421	PHASE3	UNKNOWN	Oral Cancer Screening in Mumbai, India by Primary Health Care Workers
NCT00750503	PHASE3	COMPLETED	Workplace Tobacco Cessation And Oral Cancer Screening Study
NCT00964977	PHASE3	COMPLETED	Effectiveness of Adjuvant Radiotherapy in Small Oropharyngeal Squamous Cell Cancer and Single Lymph Node Metastasis.
NCT01039298	PHASE3	UNKNOWN	Efficacy of Optically-guided Surgery in the Management of Early-staged Oral Cancer - COOLS TRIAL
NCT03685409	PHASE3	UNKNOWN	Cancer Chemoprevention by Metformin Hydrochloride in Oral Potentially Malignant Lesions
NCT05721755	PHASE3	ACTIVE_NOT_RECRUITING	Combining Radiation Therapy With Immunotherapy for the Treatment of Metastatic Squamous Cell Carcinoma of the Head and Neck
NCT06589804	PHASE3	RECRUITING	Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
NCT06737822	PHASE3	RECRUITING	Upfront Surgery Vs Induction Chemotherapy Followed By Surgery In Oral Cancers:
NCT07402538	PHASE3	NOT_YET_RECRUITING	Surgery With or Without Neoadjuvant Treatment of SBRT Plus Chemoimmunotherapy in Resectable Locally Advanced Oral and HPV-unrelated Oropharyngeal Squamous Cell Carcinoma
NCT07441681	PHASE3	NOT_YET_RECRUITING	Comparing Radiation Plus Cetuximab to Radiation Plus Chemotherapy in People With Head and Neck Cancer Who Cannot Receive Cisplatin
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00330382	PHASE2	COMPLETED	Bowman-Birk Inhibitor Concentrate in Preventing Cancer in Patients With Oral Leukoplakia
NCT00400205	PHASE2	TERMINATED	Study of Induction Docetaxel, Cisplatin and 5-Fluorouracil