SDHB

Summary

SDHB (succinate dehydrogenase complex iron sulfur subunit B, HGNC:10681) is a protein-coding gene on chromosome 1p36.13, encoding Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial (P21912). Iron-sulfur protein (IP) subunit of the succinate dehydrogenase complex (mitochondrial respiratory chain complex II), responsible for transferring electrons from succinate to ubiquinone (coenzyme Q). It is a selective cancer dependency (DepMap: 45.1% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This tumor suppressor gene encodes the iron-sulfur protein subunit of the succinate dehydrogenase (SDH) enzyme complex which plays a critical role in mitochondria. The SDH enzyme complex is composed of four nuclear-encoded subunits. This enzyme complex converts succinate to fumarate which releases electrons as part of the citric acid cycle, and the enzyme complex additionally provides an attachment site for released electrons to be transferred to the oxidative phosphorylation pathway. The SDH enzyme complex plays a role in oxygen-related gene regulation through its conversion of succinate, which is an oxygen sensor that stabilizes the hypoxia-inducible factor 1 (HIF1) transcription factor. Sporadic and familial mutations in this gene result in paragangliomas, pheochromocytoma, and gastrointestinal stromal tumors, supporting a link between mitochondrial dysfunction and tumorigenesis. Mutations in this gene are also implicated in nuclear type 4 mitochondrial complex II deficiency.

Source: NCBI Gene 6390 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +9 more curated relationships
• GWAS associations: 24
• Clinical variants (ClinVar): 1,581 total — 189 pathogenic, 65 likely-pathogenic
• Phenotypes (HPO): 214
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 45.1% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_003000

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10681
Approved symbol	SDHB
Name	succinate dehydrogenase complex iron sulfur subunit B
Location	1p36.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000117118
Ensembl biotype	protein_coding
OMIM	185470
Entrez	6390

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 9 protein_coding, 6 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000375499, ENST00000463045, ENST00000466613, ENST00000475049, ENST00000475506, ENST00000485092, ENST00000485515, ENST00000491274, ENST00000714029, ENST00000714030, ENST00000714031, ENST00000714032, ENST00000714033, ENST00000714034, ENST00000714035, ENST00000714036, ENST00000714037, ENST00000714038, ENST00000925621

RefSeq mRNA: 2 — MANE Select: NM_003000 NM_001407361, NM_003000

CCDS: CCDS176

Canonical transcript exons

ENST00000375499 — 8 exons

Exon	Start	End
ENSE00003598239	17033060	17033145
ENSE00003681743	17028600	17028736
ENSE00003728285	17044761	17044888
ENSE00003786914	17027749	17027865
ENSE00003791578	17023973	17024074
ENSE00004013903	17022608	17022730
ENSE00004022584	17018722	17018958
ENSE00004022595	17053948	17054032

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 75.8158 / max 515.5937, expressed in 1827 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10569	64.9730	1826
10570	6.2862	1735
10571	4.3962	1668
10568	0.1375	71
10567	0.0167	2
10566	0.0062	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
heart left ventricle	UBERON:0002084	98.96	gold quality
cardiac ventricle	UBERON:0002082	98.94	gold quality
apex of heart	UBERON:0002098	98.88	gold quality
gastrocnemius	UBERON:0001388	98.82	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.82	gold quality
mucosa of transverse colon	UBERON:0004991	98.80	gold quality
muscle of leg	UBERON:0001383	98.71	gold quality
heart right ventricle	UBERON:0002080	98.71	gold quality
right atrium auricular region	UBERON:0006631	98.67	gold quality
muscle organ	UBERON:0001630	98.59	gold quality
right lobe of liver	UBERON:0001114	98.54	gold quality
heart	UBERON:0000948	98.49	gold quality
vastus lateralis	UBERON:0001379	98.45	gold quality
biceps brachii	UBERON:0001507	98.45	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.45	gold quality
rectum	UBERON:0001052	98.44	gold quality
cardiac atrium	UBERON:0002081	98.44	gold quality
body of tongue	UBERON:0011876	98.42	gold quality
diaphragm	UBERON:0001103	98.28	gold quality
quadriceps femoris	UBERON:0001377	98.23	gold quality
skeletal muscle tissue	UBERON:0001134	98.20	gold quality
transverse colon	UBERON:0001157	98.20	gold quality
right adrenal gland	UBERON:0001233	98.03	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.00	gold quality
left adrenal gland	UBERON:0001234	97.95	gold quality
left adrenal gland cortex	UBERON:0035825	97.87	gold quality
right adrenal gland cortex	UBERON:0035827	97.87	gold quality
triceps brachii	UBERON:0001509	97.85	gold quality
body of stomach	UBERON:0001161	97.79	gold quality
jejunal mucosa	UBERON:0000399	97.73	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-11	no	380.49
E-MTAB-6524	no	228.89
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, HIF1A, NFE2L2, NFYA, NRF1, PLAGL1

miRNA regulators (miRDB)

44 targeting SDHB, 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-4282	99.99	75.36	6408
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-6124	99.87	69.78	3551

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 45.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas (PMID:11897817)
• Participation of the iron-sulfur protein subunit of SDHB in development of susceptibility to familial pheochromocytoma is reconfirmed by a familial case with a germline mutation. (PMID:12362046)
• Review. Succinate dehydrogenase catalyses a step in the Krebs tricarboxylic-acid cycle. Inherited heterozygous mutations in the gene encoding this enzyme causes a predisposition to inherited neoplasia syndromes. (PMID:12612654)
• SDHB has a major role in the pathogenesis of familial phaeochromocytomas, but the possible role of SDHB in sporadic tumours showing allelic loss at 1p36 has yet to be ascertained. (PMID:12618761)
• protein expression of the iron-sulfur subunit responds to the cellular iron level, thereby influencing mitochondrial respiratory function and cellular growth. (PMID:14512425)
• Germline SDHB mutations can predispose to early-onset kidney cancers in addition to paragangliomas (PMID:14685938)
• In patients with pheochromocytoma or functional paraganglioma with an SDHB mutation, the tumors were larger, more frequently extra-adrenal, and malignant. (PMID:16314641)
• A possible role for SDH polymorphism as susceptibility/disease modifying factors in familial and sporadic medullary thyroid carcinomas was shown. (PMID:16322339)
• Germline mutations of SDHB play a minor role in sporadic head and neck paraganglioma. (PMID:16405730)
• In patients with pheochromocytoma or functional paraganglioma with an SDHB mutation, the tumors were larger, more frequently extra-adrenal, and malignant. (PMID:16472267)
• Missense, nonsense, frameshift, and splice site mutations of the SDHB gene are associated with about half of all malignancies originating from extraadrenal paragangliomas. (PMID:16912137)
• Familial paraganglioma syndrome type 4 caused by a mutation in the succinate dehydrogenase complex, subunit B gene. (PMID:17143317)
• Mutations of the gene encoding succinate dehydrogenase subunit B predispose to malignant paraganglioma, but clinical expression of these tumors cannot be predicted by the genotype. (PMID:17200167)
• SDHB mutations are associated with malignant phaeochromocytoma. Patients who present with a family history of paraganglioma or phaeochromocytoma, with multiple tumours, or early onset tumours (<50 years), should be referred for genetic investigation. (PMID:17298303)
• Two novel SDH mutations in Japanese pheochromocytomas. (PMID:17308434)
• SDHB mutations are associated with a high rate of malignant head and neck paragangliomas. (PMID:17599579)
• SDHB mutations, frequent in patients with malignant pheochromocytomas or paragangliomas, are associated with shorter survival (PMID:17652212)
• investigated 11 patients with the dyad of ‘paraganglioma and gastric stromal sarcoma’; in eight, from 7 unrelated families, the GISTs were caused by germline mutations of the genes encoding subunits B, C, or D (the SDHB, SDHC and SDHD genes, respectively) (PMID:17667967)
• familial gastrointestinal stromal tumors may be caused by mutations of the succinate dehydrogenase subunit genes SDHB, SDHC, and SDHD (PMID:17804857)
• Molecular genetic analysis with sequencing of the succinate dehydrogenase type B (SDHB) gene revealed a unknown mutation of codon 214 (CAG–>TAG) leading to an amino acid change of glutamine to a stop-Codon (Q214X-mutation) in exon 6 in pheochromocytoma. (PMID:17943698)
• differences in reactive oxygen species production, HIF proliferation, and cell proliferation contribute to the differences in tumor phenotype in cells lacking SdhB as opposed to those lacking SdhA (PMID:17967865)
• After haplotyping the SDHB region, we concluded that the deletion detected in Iberian Peninsular paraganglioma patients is probably due to a founder effect. (PMID:18057081)
• Mutation of succinate dehydrogenase enzyme subunit B gene is associated with metastatic pheochromocytoma and paraganglioma (PMID:18310297)
• There is a pathogenic role of the succinate dehydrogenase B mutation (R46Q) in malignant paraganglioma. (PMID:18362451)
• An excess of SDHB mutations in paragangliomas versus pheochromocytomas was found, with no difference in the frequency of mutations in malignant versus benign paragangliomas. (PMID:18382370)
• SDH-B mutation carriers develop disease early and predominantly in extra-adrenal locations. (PMID:18419787)
• transient silencing of the HIF-1 alpha transcription factor in SDHB-silenced cells had little effect on expression of a subset of up-regulated genes, it partially reversed adhesion phenotype to fibronectin, indicating a role for HIF-1 in this process (PMID:18519664)
• In this Belgian series there is a high frequency of SDHB mutations associated with head and neck paragangliomas without evidence of recurrence or malignancy. (PMID:18551016)
• analysis of germline mutations and variants in the succinate dehydrogenase genes SDHB and SDHD in Cowden and Cowden-like syndromes (PMID:18678321)
• Germline mutations of the SDHB gene may be associated with genetic susceptibility to renal cell carcinoma. Thus, inherited mutations in SDHB may predispose individuals to RCC. (PMID:18728283)
• mediastinal paragangliomas are strongly associated with SDHB gene mutations (PMID:19075037)
• Malignant paraganglioma associated with SDHB is reported in an 8-year-old child. When should genetic screening start? (PMID:19189136)
• SDHB mutations are associated with extra-adrenal paragangliomas. (PMID:19208735)
• we report the case of a novel SDHB mutation (L157X) in a Japanese patient with abdominal paraganglioma following malignant lung metastasis. In addition, we identified an asymptomatic carrier of the SDHB mutation in this family. (PMID:19261994)
• A novel deletion of exon 3 of the SDHB gene was identified in nine apparently unrelated Dutch patients (PMID:19368708)
• Variable expressivity of the phenotype associated with a large exon 1 SDHB deletion, including low penetrance, diverse primary paraganglioma tumor locations, and malignant potential (PMID:19389109)
• Fifteen cases of PGL carried a germline mutation in SDHB or SDHD, four of which not described before. (PMID:19393419)
• Multiple genetic alterations including mutations, polymorphisms and intronic variants are more frequently observed in malignant pheochromocytomas. (PMID:19399650)
• no clear association was found between gene variants involved in oxygen sensing and chemoresponsiveness, although some mutations in the SDHB and SDHD genes deserve further investigations in a larger population. (PMID:19768395)
• We report tumor risks in 358 patients with SDHB (n=295) and SDHD (n=63) mutations for head and neck paragangliomas (HNPGL), adrenal pheochromocytoma and renal tumors. (PMID:19802898)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-31b16.7	ENSDARG00000092713
mus_musculus	Sdhb	ENSMUSG00000009863
rattus_norvegicus	Sdhb	ENSRNOG00000007967
drosophila_melanogaster	SdhB	FBGN0014028
drosophila_melanogaster	SdhBL	FBGN0030975
caenorhabditis_elegans		WBGENE00006433
caenorhabditis_elegans		WBGENE00009626

Protein

Protein identifiers

Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial — P21912 (reviewed: P21912)

Alternative names: Iron-sulfur subunit of complex II, Malate dehydrogenase [quinone] iron-sulfur subunit

All UniProt accessions (13): A0A087WWT1, A0A087WXX8, A0AAQ5BH73, A0AAQ5BH80, A0AAQ5BH88, A0AAQ5BHA5, A0AAQ5BHB4, A0AAQ5BHC2, A0AAQ5BHC5, A0AAQ5BHC9, A0AAQ5BHD9, A0AAQ5BHE6, P21912

UniProt curated annotations — full annotation on UniProt →

Function. Iron-sulfur protein (IP) subunit of the succinate dehydrogenase complex (mitochondrial respiratory chain complex II), responsible for transferring electrons from succinate to ubiquinone (coenzyme Q). SDH also oxidizes malate to the non-canonical enol form of oxaloacetate, enol-oxaloacetate. Enol-oxaloacetate, which is a potent inhibitor of the succinate dehydrogenase activity, is further isomerized into keto-oxaloacetate.

Subunit / interactions. Component of complex II composed of four subunits: the flavoprotein (FP) SDHA, iron-sulfur protein (IP) SDHB, and a cytochrome b560 composed of SDHC and SDHD. Interacts with SDHAF1; the interaction is required for iron-sulfur cluster incorporation into SDHB. (Microbial infection) Interacts with JC virus small t antigen.

Subcellular location. Mitochondrion inner membrane.

Disease relevance. Pheochromocytoma/paraganglioma syndrome 4 (PPGL4) [MIM:115310] A form of pheochromocytoma/paraganglioma syndrome, a tumor predisposition syndrome characterized by the development of neuroendocrine tumors, usually in adulthood. Pheochromocytomas are catecholamine-producing tumors that arise from chromaffin cells in the adrenal medulla. Paragangliomas develop from sympathetic paraganglia in the thorax, abdomen, and pelvis, as well as from parasympathetic paraganglia in the head and neck. PPGL4 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. Paraganglioma and gastric stromal sarcoma (PGGSS) [MIM:606864] Gastrointestinal stromal tumors may be sporadic or inherited in an autosomal dominant manner, alone or as a component of a syndrome associated with other tumors, such as in the context of neurofibromatosis type 1 (NF1). Patients have both gastrointestinal stromal tumors and paragangliomas. Susceptibility to the tumors was inherited in an apparently autosomal dominant manner, with incomplete penetrance. The disease is caused by variants affecting the gene represented in this entry. Mitochondrial complex II deficiency, nuclear type 4 (MC2DN4) [MIM:619224] A form of mitochondrial complex II deficiency, a disorder with heterogeneous clinical manifestations. Some patients have multisystem involvement of the brain, heart, muscle, liver, and kidneys resulting in death in infancy, whereas others have only isolated cardiac or muscle involvement with onset in adulthood and normal cognition. Clinical features include psychomotor regression in infants, poor growth with lack of speech development, severe spastic quadriplegia, dystonia, progressive leukoencephalopathy, muscle weakness, exercise intolerance, cardiomyopathy. Some patients manifest Leigh syndrome or Kearns-Sayre syndrome. MC2DN4 is a severe, autosomal recessive form characterized by early-onset progressive neurodegeneration with leukoencephalopathy. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Enol-oxaloacetate inhibits the succinate dehydrogenase activity.

Cofactor. Binds 1 [2Fe-2S] cluster. Binds 1 [3Fe-4S] cluster. Binds 1 [4Fe-4S] cluster.

Pathway. Carbohydrate metabolism; tricarboxylic acid cycle; fumarate from succinate (eukaryal route): step 1/1.

Similarity. Belongs to the succinate dehydrogenase/fumarate reductase iron-sulfur protein family.

RefSeq proteins (2): NP_001394290, NP_002991* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001041	2Fe-2S_ferredoxin-type	Domain
IPR004489	Succ_DH/fum_Rdtase_Fe-S	Family
IPR006058	2Fe2S_fd_BS	Binding_site
IPR009051	Helical_ferredxn	Homologous_superfamily
IPR012675	Beta-grasp_dom_sf	Homologous_superfamily
IPR017896	4Fe4S_Fe-S-bd	Domain
IPR017900	4Fe4S_Fe_S_CS	Conserved_site
IPR025192	Succ_DH/fum_Rdtase_N	Domain
IPR036010	2Fe-2S_ferredoxin-like_sf	Homologous_superfamily
IPR050573	SDH/FRD_Iron-Sulfur	Family

Pfam: PF13085, PF13534

Enzyme classification (BRENDA):

• EC 1.3.5.1 — succinate dehydrogenase (BRENDA: 80 organisms, 226 substrates, 192 inhibitors, 145 Km, 115 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
SUCCINATE	0.0015–20	39
UBIQUINONE	0.0005–0.2	26
FUMARATE	0.005–0.455	14
2,3-DIMETHOXY-5-METHYL-6-DECYL-1,4-BENZOQUINONE	0.0034–0.018	9
REDUCED PLUMBAGIN	0.11–0.19	9
UBIQUINONE-2	0.0002–0.0114	9
MENAQUINOL	0.0009–0.0054	8
PHENAZINE METHOSULFATE	0.11–0.48	3
UBIQUINONE-1	0.0016–0.02	3
2,6-DICHLOROPHENOL INDOPHENOL	0.003–0.007	2
CALDARIELLAQUINONE	0.06–0.18	2
MENAQUINONE	0.0018–0.004	2
OXIDIZED 2,6-DICHLOROPHENOLINDOPHENOL	0.0654–0.089	2
2,3-DIMETHOXY-5-METHYL-1,4-BENZOQUINONE	0.003	1
2,3-DIMETHYL-1,4-NAPHTHOHYDROQUINONE	0.12	1

Catalyzed reactions (Rhea), 3 shown:

• a quinone + succinate = fumarate + a quinol (RHEA:40523)
• (R)-malate + a quinone = enol-oxaloacetate + a quinol (RHEA:79827)
• (S)-malate + a quinone = enol-oxaloacetate + a quinol (RHEA:79831)

UniProt features (76 total): sequence variant 26, binding site 12, strand 10, helix 10, turn 6, sequence conflict 5, modified residue 2, domain 2, transit peptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
9KC4	ELECTRON MICROSCOPY	2.65
8GS8	ELECTRON MICROSCOPY	2.86
7KLV	ELECTRON MICROSCOPY	3.1
7KCL	ELECTRON MICROSCOPY	3.14
7KCM	ELECTRON MICROSCOPY	3.43
7KLU	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21912-F1	92.14	0.86

Functional residue map

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

Ligand- & substrate-binding residues (12): 189; 192; 196; 201; 243; 249; 253; 93; 98; 101; 113; 186

Post-translational modifications (2): 51, 55

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-611105	Respiratory electron transport
R-HSA-71403	Citric acid cycle (TCA cycle)
R-HSA-9854311	Maturation of TCA enzymes and regulation of TCA cycle
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism

MSigDB gene sets: 643 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, MODULE_151, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, MORF_HDAC1, MORF_UBE2N, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, CREBP1_Q2, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, MORF_HDAC2, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS

GO Biological Process (6): tricarboxylic acid cycle (GO:0006099), succinate metabolic process (GO:0006105), mitochondrial electron transport, succinate to ubiquinone (GO:0006121), aerobic respiration (GO:0009060), respiratory electron transport chain (GO:0022904), proton motive force-driven mitochondrial ATP synthesis (GO:0042776)

GO Molecular Function (10): succinate dehydrogenase (quinone) activity (GO:0008177), electron transfer activity (GO:0009055), metal ion binding (GO:0046872), ubiquinone binding (GO:0048039), 2 iron, 2 sulfur cluster binding (GO:0051537), 3 iron, 4 sulfur cluster binding (GO:0051538), 4 iron, 4 sulfur cluster binding (GO:0051539), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (8): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), plasma membrane (GO:0005886), mitochondrial membrane (GO:0031966), respiratory chain complex II (succinate dehydrogenase) (GO:0045273), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Aerobic respiration and respiratory electron transport	2
Citric acid cycle (TCA cycle)	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	3
iron-sulfur cluster binding	3
cellular respiration	2
cellular anatomical structure	2
aerobic respiration	1
primary metabolic process	1
dicarboxylic acid metabolic process	1
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
electron transport chain	1
oxidative phosphorylation	1
proton motive force-driven ATP synthesis	1
succinate dehydrogenase activity	1
oxidoreductase activity, acting on the CH-CH group of donors, quinone or related compound as acceptor	1
molecular_function	1
cation binding	1
quinone binding	1
binding	1
catalytic activity	1
metal cluster binding	1
nuclear lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
mitochondrial envelope	1
organelle membrane	1
membrane protein complex	1
respiratory chain complex	1
oxidoreductase complex	1

Protein interactions and networks

STRING

5057 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SDHB	SDHA	P31040	999
SDHB	SDHC	Q99643	999
SDHB	SDHD	O14521	999
SDHB	SDHAF2	Q9NX18	998
SDHB	F5H5T6	F5H5T6	994
SDHB	UQCRC2	P22695	977
SDHB	SDHAF1	A6NFY7	959
SDHB	NDUFB8	O95169	953
SDHB	TMEM127	O75204	935
SDHB	FH	P07954	893
SDHB	RET	P07949	884
SDHB	MT-CO1	P00395	877
SDHB	MT-CYB	P00156	847
SDHB	NF1	P21359	823
SDHB	ATP5F1A	P25705	811

IntAct

153 interactions, top by confidence:

A	B	Type	Score
HSCB	SDHB	psi-mi:“MI:0407”(direct interaction)	0.820
SDHB	SDHA	psi-mi:“MI:0914”(association)	0.820
HSCB	SDHB	psi-mi:“MI:0915”(physical association)	0.820
HSCB	SDHB	psi-mi:“MI:0914”(association)	0.820
SDHA	SDHB	psi-mi:“MI:0914”(association)	0.820
SDHA	SDHB	psi-mi:“MI:0915”(physical association)	0.820
SDHB	SDHA	psi-mi:“MI:0915”(physical association)	0.820
SDHAF1	SDHB	psi-mi:“MI:0914”(association)	0.790
SDHAF1	SDHB	psi-mi:“MI:0915”(physical association)	0.790
SDHAF1	SDHB	psi-mi:“MI:0407”(direct interaction)	0.790
SDHB	SDHAF1	psi-mi:“MI:0914”(association)	0.790
SDHB	SDHAF1	psi-mi:“MI:0915”(physical association)	0.790

BioGRID (261): SDHB (Affinity Capture-MS), AGL (Co-fractionation), ATP6AP2 (Co-fractionation), CISD1 (Co-fractionation), COX4I1 (Co-fractionation), DLAT (Co-fractionation), GPD2 (Co-fractionation), GPI (Co-fractionation), ILVBL (Co-fractionation), MRPL45 (Co-fractionation), COX2 (Co-fractionation), NDUFA12 (Co-fractionation), NDUFA2 (Co-fractionation), NDUFA6 (Co-fractionation), NDUFB9 (Co-fractionation)

ESM2 similar proteins: A5PL98, A8WPF0, A9NNH7, B0BM36, O06914, O42772, O44074, P07014, P08066, P0AC47, P0AC48, P0AC49, P0AC50, P17596, P20921, P21801, P21911, P21912, P21913, P21914, P32420, P44893, P51053, P80480, P9WN88, P9WN89, Q007T0, Q09545, Q1RGP3, Q3B8J8, Q3T189, Q4UN71, Q54I90, Q55CC2, Q59662, Q68XS0, Q6FWS8, Q6H4G3, Q70KF8, Q75CI4

Diamond homologs: A5PL98, A8WPF0, B0BM36, D9PUX5, O42772, O44074, P07014, P0AC47, P0AC48, P0AC49, P0AC50, P17596, P20921, P21801, P21911, P21912, P21913, P21914, P32420, P48932, P48933, P51053, P80477, P80480, P9WN88, P9WN89, Q007T0, Q09545, Q1RGP3, Q3B8J8, Q3T189, Q4UN71, Q55CC2, Q57557, Q59662, Q68XS0, Q6FWS8, Q6H4G3, Q6LYC4, Q70KF8

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
SDHAF2	up-regulates	SDHB	binding
SDHB	“form complex”	“Succinate dehydrogenase-Mitochondrial respiratory chain complex II”	binding
“iron-sulfur cluster”	“up-regulates activity”	SDHB	“chemical activation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 109 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Maturation of TCA enzymes and regulation of TCA cycle	7	50.0×	3e-08
Citric acid cycle (TCA cycle)	5	26.4×	2e-04
Mitochondrial protein import	7	14.7×	1e-04
Mitochondrial protein degradation	7	10.0×	9e-04
PIP3 activates AKT signaling	8	6.7×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
iron-sulfur cluster assembly	5	31.0×	2e-04
cellular response to epidermal growth factor stimulus	5	16.4×	3e-03
epidermal growth factor receptor signaling pathway	6	15.3×	8e-04
phosphatidylinositol 3-kinase/protein kinase B signal transduction	7	15.2×	2e-04
positive regulation of miRNA transcription	5	15.0×	3e-03
protein import into nucleus	6	8.9×	7e-03
cell population proliferation	7	7.4×	6e-03
positive regulation of ERK1 and ERK2 cascade	8	7.0×	3e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

1581 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	189
Likely pathogenic	65
Uncertain significance	685
Likely benign	340
Benign	48

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1065988	NM_003000.3(SDHB):c.200+1G>C	Pathogenic
1066588	NM_003000.3(SDHB):c.557G>A (p.Cys186Tyr)	Pathogenic
1069440	NM_003000.3(SDHB):c.412del (p.Asp138fs)	Pathogenic
1070347	NM_003000.3(SDHB):c.466del (p.Tyr156fs)	Pathogenic
1072823	NC_000001.10:g.(?17345376)(17345463_?)del	Pathogenic
1072824	NC_000001.10:g.(?17345376)(17371403_?)del	Pathogenic
1074491	NM_003000.3(SDHB):c.17_18insACTCTCCTTGAGGCGCCGGTTGC (p.Ala15fs)	Pathogenic
1176539	GRCh37/hg19 1p36.13(chr1:17345376-17345453)x1	Pathogenic
12778	NM_003000.3(SDHB):c.268C>T (p.Arg90Ter)	Pathogenic
12782	NM_003000.3(SDHB):c.716_719del (p.Ser239fs)	Pathogenic
12783	NM_003000.3(SDHB):c.79C>T (p.Arg27Ter)	Pathogenic
12784	NM_003000.3(SDHB):c.(-151_-1)_(72+1_73-1)del	Pathogenic
12785	NM_003000.3(SDHB):c.136C>G (p.Arg46Gly)	Pathogenic
12790	NM_003000.3(SDHB):c.423+1G>C	Pathogenic
1285202	NM_003000.3(SDHB):c.200+1G>A	Pathogenic
1326294	NM_003000.3(SDHB):c.423+1G>T	Pathogenic
1362479	NC_000001.10:g.(?17345376)(17359650_?)del	Pathogenic
1363102	NM_003000.3(SDHB):c.598del (p.Trp200fs)	Pathogenic
1371694	NM_003000.3(SDHB):c.445_446dup (p.Gln149fs)	Pathogenic
1380234	NM_003000.3(SDHB):c.183T>A (p.Tyr61Ter)	Pathogenic
1381081	NM_003000.3(SDHB):c.19_41dup (p.Pro14_Ala15insSerProTer)	Pathogenic
1400077	NM_003000.3(SDHB):c.484G>T (p.Glu162Ter)	Pathogenic
140773	NM_003000.3(SDHB):c.286+2T>A	Pathogenic
142653	NM_003000.3(SDHB):c.607_616del (p.Gly203fs)	Pathogenic
142763	NM_003000.3(SDHB):c.136C>T (p.Arg46Ter)	Pathogenic
1443907	NM_003000.3(SDHB):c.450C>G (p.Tyr150Ter)	Pathogenic
1452759	NM_003000.3(SDHB):c.743_765+36del	Pathogenic
1455650	NC_000001.10:g.(?17349093)(17380514_?)del	Pathogenic
1455849	NM_003000.3(SDHB):c.243_246dup (p.Val83Ter)	Pathogenic
1456331	NM_003000.3(SDHB):c.75del (p.Ser26fs)	Pathogenic

SpliceAI

1255 predictions. Top by Δscore:

Variant	Effect	Δscore
1:17018958:CCT:C	acceptor_gain	1.0000
1:17018960:T:C	acceptor_gain	1.0000
1:17022603:CGTA:C	donor_loss	1.0000
1:17022604:GTA:G	donor_loss	1.0000
1:17022605:TAC:T	donor_loss	1.0000
1:17022606:ACC:A	donor_loss	1.0000
1:17022607:C:CT	donor_loss	1.0000
1:17022726:TAGGC:T	acceptor_gain	1.0000
1:17022728:GGCC:G	acceptor_loss	1.0000
1:17022729:GCCTG:G	acceptor_loss	1.0000
1:17022730:CCTGG:C	acceptor_loss	1.0000
1:17022731:C:CC	acceptor_gain	1.0000
1:17022731:CTGG:C	acceptor_loss	1.0000
1:17022732:T:A	acceptor_loss	1.0000
1:17027758:A:AC	donor_gain	1.0000
1:17027759:C:CC	donor_gain	1.0000
1:17027759:CG:C	donor_gain	1.0000
1:17027759:CGCT:C	donor_gain	1.0000
1:17027795:T:A	donor_gain	1.0000
1:17028598:A:AC	donor_gain	1.0000
1:17028599:C:CC	donor_gain	1.0000
1:17033143:CAT:C	acceptor_gain	1.0000
1:17044753:ATACT:A	donor_loss	1.0000
1:17044757:TCA:T	donor_loss	1.0000
1:17044758:CACTT:C	donor_loss	1.0000
1:17044759:A:AC	donor_gain	1.0000
1:17044760:C:CA	donor_gain	1.0000
1:17044760:CT:C	donor_gain	1.0000
1:17044760:CTT:C	donor_gain	1.0000
1:17044760:CTTA:C	donor_gain	1.0000

AlphaMissense

1835 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:17022646:A:G	C243R	1.000
1:17024029:A:G	C196R	1.000
1:17024059:A:G	C186R	1.000
1:17022614:A:C	C253W	0.999
1:17022615:C:T	C253Y	0.999
1:17022616:A:G	C253R	0.999
1:17022626:G:C	C249W	0.999
1:17022627:C:T	C249Y	0.999
1:17022628:A:G	C249R	0.999
1:17022644:G:C	C243W	0.999
1:17022645:C:A	C243F	0.999
1:17022645:C:G	C243S	0.999
1:17022645:C:T	C243Y	0.999
1:17022646:A:T	C243S	0.999
1:17022704:T:A	R223S	0.999
1:17022704:T:G	R223S	0.999
1:17022705:C:A	R223I	0.999
1:17022705:C:G	R223T	0.999
1:17022721:A:G	W218R	0.999
1:17022721:A:T	W218R	0.999
1:17022723:C:G	R217P	0.999
1:17022724:G:T	R217S	0.999
1:17023992:C:T	G208E	0.999
1:17023993:C:G	G208R	0.999
1:17023993:C:T	G208R	0.999
1:17024021:G:C	S198R	0.999
1:17024021:G:T	S198R	0.999
1:17024023:T:G	S198R	0.999
1:17024027:G:C	C196W	0.999
1:17024028:C:T	C196Y	0.999

dbSNP variants (sampled 300 via entrez): RS1000040715 (1:17035471 C>T), RS1000158338 (1:17047868 T>C,G), RS1000341001 (1:17030102 T>G), RS1000501757 (1:17036787 C>A,T), RS1000507925 (1:17018668 A>C,G), RS1000582771 (1:17024680 G>A), RS1000694609 (1:17042818 C>T), RS1000760553 (1:17049557 A>G), RS1000786527 (1:17031260 G>C), RS1000965442 (1:17049301 CTTTT>C,CTTT,CTTTTT,CTTTTTT), RS1001036889 (1:17055138 G>A), RS1001173587 (1:17023622 C>T), RS1001191146 (1:17049829 T>C,G), RS1001293246 (1:17048749 C>A,G,T), RS1001314422 (1:17054248 C>A,G,T)

Disease associations

OMIM: gene MIM:185470 | disease phenotypes: MIM:115310, MIM:171300, MIM:606764, MIM:168000, MIM:193300, MIM:606864, MIM:619224, MIM:158350, MIM:604287, MIM:167000, MIM:252011

GenCC curated gene-disease

Disease	Classification	Inheritance
pheochromocytoma/paraganglioma syndrome 4	Definitive	Autosomal dominant
hereditary pheochromocytoma-paraganglioma	Definitive	Autosomal dominant
gastrointestinal stromal tumor	Definitive	Autosomal dominant
Carney-Stratakis syndrome	Definitive	Autosomal dominant
pheochromocytoma	Definitive	Autosomal dominant
renal cell carcinoma	Strong	Autosomal dominant
mitochondrial complex 2 deficiency, nuclear type 4	Strong	Autosomal recessive
Cowden disease	Supportive	Autosomal dominant
mitochondrial complex II deficiency	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
mitochondrial disease	Definitive	AR
hereditary pheochromocytoma-paraganglioma	Definitive	AD

Mondo (19): pheochromocytoma/paraganglioma syndrome 4 (MONDO:0007273), pheochromocytoma (MONDO:0008233), gastrointestinal stromal tumor (MONDO:0011719), hereditary neoplastic syndrome (MONDO:0015356), hereditary pheochromocytoma-paraganglioma (MONDO:0017366), von Hippel-Lindau disease (MONDO:0008667), Carney-Stratakis syndrome (MONDO:0011740), mitochondrial complex 2 deficiency, nuclear type 4 (MONDO:0030974), Cowden disease (MONDO:0016063), breast cancer (MONDO:0007254), paraganglioma (MONDO:0000448), renal cell carcinoma (MONDO:0005086), Carney triad (MONDO:0011424), Cowden syndrome 1 (MONDO:0008021), ovarian cancer (MONDO:0008170)

Orphanet (11): Inherited cancer-predisposing syndrome (Orphanet:140162), Hereditary pheochromocytoma-paraganglioma (Orphanet:29072), Gastrointestinal stromal tumor (Orphanet:44890), Von Hippel-Lindau disease (Orphanet:892), Carney-Stratakis syndrome (Orphanet:97286), Cowden syndrome (Orphanet:201), Renal cell carcinoma (Orphanet:217071), Carney triad (Orphanet:139411), Rare ovarian cancer (Orphanet:213500), Hereditary papillary renal cell carcinoma (Orphanet:47044), Isolated succinate-CoQ reductase deficiency (Orphanet:3208)

HPO phenotypes

214 total (30 of 214 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000036	Abnormal penis morphology
HP:0000076	Vesicoureteral reflux
HP:0000077	Abnormality of the kidney
HP:0000093	Proteinuria
HP:0000096	Glomerular sclerosis
HP:0000130	Abnormality of the uterus
HP:0000158	Macroglossia
HP:0000218	High palate
HP:0000221	Furrowed tongue
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000360	Tinnitus
HP:0000365	Hearing impairment
HP:0000405	Conductive hearing impairment
HP:0000478	Abnormality of the eye
HP:0000518	Cataract
HP:0000526	Aniridia
HP:0000544	External ophthalmoplegia
HP:0000545	Myopia
HP:0000580	Pigmentary retinopathy
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000717	Autism
HP:0000726	Dementia
HP:0000737	Irritability
HP:0000740	Episodic paroxysmal anxiety
HP:0000750	Delayed speech and language development
HP:0000767	Pectus excavatum

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST000611_7	Height	2.000000e-07
GCST010696_16	Cortical thickness (min-P)	8.000000e-11
GCST010697_21	Cortical surface area (min-P)	1.000000e-08
GCST010698_46	Subcortical volume (min-P)	2.000000e-11
GCST010699_5	Brain morphology (min-P)	7.000000e-11
GCST010700_46	Cortical thickness (MOSTest)	2.000000e-10
GCST010701_63	Cortical surface area (MOSTest)	3.000000e-14
GCST010702_161	Subcortical volume (MOSTest)	2.000000e-20
GCST010703_70	Brain morphology (MOSTest)	2.000000e-08
GCST012226_410	Waist circumference adjusted for body mass index	2.000000e-08
GCST012226_411	Waist circumference adjusted for body mass index	4.000000e-14
GCST012226_412	Waist circumference adjusted for body mass index	1.000000e-08
GCST012226_413	Waist circumference adjusted for body mass index	1.000000e-12
GCST012227_1377	Hip circumference adjusted for BMI	1.000000e-12
GCST012227_1379	Hip circumference adjusted for BMI	4.000000e-14
GCST012227_1380	Hip circumference adjusted for BMI	2.000000e-15
GCST90020024_4	A body shape index	2.000000e-11
GCST90020024_5	A body shape index	5.000000e-10
GCST90020024_6	A body shape index	5.000000e-12
GCST90020028_565	Hip circumference adjusted for BMI	2.000000e-09
GCST90020028_660	Hip circumference adjusted for BMI	1.000000e-14
GCST90020028_664	Hip circumference adjusted for BMI	2.000000e-08
GCST90020029_1249	Waist circumference adjusted for body mass index	1.000000e-13
GCST90020029_1250	Waist circumference adjusted for body mass index	2.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (11)

Descriptor	Name	Tree numbers
D002292	Carcinoma, Renal Cell	C04.557.470.200.025.390; C04.588.945.947.535.160; C12.050.351.937.820.535.160; C12.050.351.968.419.473.160; C12.200.758.820.750.160; C12.200.777.419.473.160; C12.900.820.535.160; C12.950.419.473.160; C12.950.983.535.160
D046152	Gastrointestinal Stromal Tumors	C04.557.450.565.370; C06.301.371.308; C06.405.249.308
D006223	Hamartoma Syndrome, Multiple	C04.445.435; C04.651.435; C04.700.435; C16.320.700.435
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D010235	Paraganglioma	C04.557.465.625.650.700; C04.557.580.625.650.700
D010673	Pheochromocytoma	C04.557.465.625.650.700.725; C04.557.580.625.650.700.725
D006623	von Hippel-Lindau Disease	C10.562.925; C14.907.077.925; C16.131.077.245.750; C16.320.184.750
C565803	Carney Triad (supp.)
C564650	Carney-Stratakis Syndrome (supp.)
C565375	Mitochondrial Complex II Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105824 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

4 measured of 4 human assays (4 total across all organisms); most potent 4 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-(1-adamantyl)-4-[4-[1-[(3,4-dimethoxyphenyl)methyl]-6-oxo-3-pyridinyl]-6-(trifluoromethyl)pyrimidin-2-yl]sulfonylbutanamide	EC50	500 nM	US-11725000: Apoptosis inhibitors
N-(1-adamantyl)-4-[4-(difluoromethyl)-6-[1-[(3,4-dimethoxyphenyl)methyl]-6-oxo-3-pyridinyl]pyrimidin-2-yl]sulfonylbutanamide	EC50	500 nM	US-11725000: Apoptosis inhibitors
N-(1-adamantyl)-4-[4-[1-(1,3-benzodioxol-5-ylmethyl)-5-fluoro-6-oxo-3-pyridinyl]-6-methylpyrimidin-2-yl]sulfonylbutanamide	EC50	500 nM	US-11725000: Apoptosis inhibitors
N-(1-adamantyl)-4-[4-[5-fluoro-1-[(3-methylbenzotriazol-5-yl)methyl]-6-oxo-3-pyridinyl]-6-methylpyrimidin-2-yl]sulfonylbutanamide	EC50	500 nM	US-11725000: Apoptosis inhibitors

ChEMBL bioactivities

36 potent at pChembl≥5 of 39 total, top 36 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.64	EC50	0.23	nM	CHEMBL4078870
9.38	EC50	0.42	nM	CHEMBL4078870
8.85	EC50	1.4	nM	CHEMBL4078220
7.60	EC50	25	nM	CHEMBL4091379
7.57	EC50	27	nM	CHEMBL4064603
7.24	EC50	57	nM	CHEMBL4070501
7.18	EC50	66	nM	CHEMBL4061878
7.16	EC50	69	nM	CHEMBL4092330
7.03	EC50	94	nM	CHEMBL4082074
6.96	EC50	110	nM	CHEMBL4071549
6.79	EC50	164	nM	CHEMBL4086114
6.67	EC50	216	nM	CHEMBL4093871
6.60	EC50	253	nM	CHEMBL4083596
6.59	EC50	257	nM	CHEMBL4089942
6.55	EC50	282	nM	CHEMBL4073188
6.44	EC50	364	nM	CHEMBL4101603
6.13	EC50	749	nM	CHEMBL1430895
6.09	EC50	817	nM	CHEMBL4101046
5.95	EC50	1135	nM	CHEMBL4070722
5.94	EC50	1143	nM	CHEMBL4063455
5.94	EC50	1157	nM	CHEMBL4085084
5.84	EC50	1428	nM	CHEMBL4097841
5.80	EC50	1591	nM	CHEMBL4090123
5.74	EC50	1821	nM	CHEMBL4097672
5.66	EC50	2201	nM	CHEMBL1492648
5.46	EC50	3489	nM	CHEMBL4063532
5.46	EC50	3487	nM	CHEMBL4096202
5.45	EC50	3516	nM	CHEMBL4086039
5.40	EC50	4000	nM	CHEMBL4103147
5.39	EC50	4060	nM	CHEMBL4074296
5.38	EC50	4207	nM	CHEMBL4062092
5.35	EC50	4477	nM	CHEMBL4100077
5.20	EC50	6355	nM	CHEMBL4078150
5.18	EC50	6642	nM	CHEMBL4104624
5.15	EC50	7033	nM	CHEMBL4103961
5.06	EC50	8756	nM	CHEMBL4088482

PubChem BioAssay actives

36 with measured affinity, of 60 total; 35 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(1-adamantyl)-4-[4-[1-[(3,4-dimethoxyphenyl)methyl]-6-oxo-3-pyridinyl]-6-(trifluoromethyl)pyrimidin-2-yl]sulfonylbutanamide	1427665: Inhibition of SDHB in human U2OS cells over-expressing tBid assessed as reduction in apoptosis preincubated for 1 hr followed by doxycyclin addition to induce tBid protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	0.0002	uM
1-[(3,4-dimethoxyphenyl)methyl]-5-[2-(4-oxo-4-piperidin-1-ylbutyl)sulfonyl-6-(trifluoromethyl)pyrimidin-4-yl]pyridin-2-one	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	0.0014	uM
1-[(3,4-dimethoxyphenyl)methyl]-5-[2-methylsulfonyl-6-(trifluoromethyl)pyrimidin-4-yl]pyridin-2-one	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	0.0250	uM
1-[(3,4-dimethoxyphenyl)methyl]-5-[2-(4-oxo-4-pyrrolidin-1-ylbutyl)sulfonyl-6-(trifluoromethyl)pyrimidin-4-yl]pyridin-2-one	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	0.0270	uM
1-[(3-methoxyphenyl)methyl]-5-[2-methylsulfonyl-6-(trifluoromethyl)pyrimidin-4-yl]pyridin-2-one	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	0.0570	uM
1-[(4-chlorophenyl)methyl]-5-[2-methylsulfonyl-6-(trifluoromethyl)pyrimidin-4-yl]pyridin-2-one	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	0.0660	uM
5-[2-methylsulfonyl-6-(trifluoromethyl)pyrimidin-4-yl]-1-[(3-propoxyphenyl)methyl]pyridin-2-one	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	0.0690	uM
1-[(4-methoxyphenyl)methyl]-5-[2-methylsulfonyl-6-(trifluoromethyl)pyrimidin-4-yl]pyridin-2-one	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	0.0940	uM
1-[(3-ethoxyphenyl)methyl]-5-[2-methylsulfonyl-6-(trifluoromethyl)pyrimidin-4-yl]pyridin-2-one	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	0.1100	uM
4-[4-[1-[(3,4-dimethoxyphenyl)methyl]-6-oxo-3-pyridinyl]-6-(trifluoromethyl)pyrimidin-2-yl]sulfonyl-N,N-dimethylbutanamide	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	0.1640	uM
1-[(3,4-dimethoxyphenyl)methyl]-5-[2-(2-methoxyethylsulfonyl)-6-(trifluoromethyl)pyrimidin-4-yl]pyridin-2-one	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	0.2160	uM
1-[(3,4-dimethoxyphenyl)methyl]-5-[2-heptylsulfonyl-6-(trifluoromethyl)pyrimidin-4-yl]pyridin-2-one	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	0.2530	uM
1-[(3-chlorophenyl)methyl]-5-[2-methylsulfonyl-6-(trifluoromethyl)pyrimidin-4-yl]pyridin-2-one	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	0.2570	uM
1-[(3,4-dimethoxyphenyl)methyl]-5-[2-(3-methoxypropylsulfonyl)-6-(trifluoromethyl)pyrimidin-4-yl]pyridin-2-one	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	0.2820	uM
1-[(3,4-dimethoxyphenyl)methyl]-5-[2-pentylsulfonyl-6-(trifluoromethyl)pyrimidin-4-yl]pyridin-2-one	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	0.3640	uM
2-methylsulfonyl-4-thiophen-2-yl-6-(trifluoromethyl)pyrimidine	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	0.7490	uM
1-[(4-ethynylphenyl)methyl]-5-[2-methylsulfonyl-6-(trifluoromethyl)pyrimidin-4-yl]pyridin-2-one	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	0.8170	uM
ethyl 3-[4-thiophen-2-yl-6-(trifluoromethyl)pyrimidin-2-yl]sulfonylpropanoate	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	1.1350	uM
1-[(2-chlorophenyl)methyl]-5-[2-methylsulfonyl-6-(trifluoromethyl)pyrimidin-4-yl]pyridin-2-one	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	1.1430	uM
1-benzyl-5-[2-methylsulfonyl-6-(trifluoromethyl)pyrimidin-4-yl]pyridin-2-one	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	1.1570	uM
2-ethylsulfonyl-4-thiophen-2-yl-6-(trifluoromethyl)pyrimidine	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	1.4280	uM
2-(2-phenylethylsulfonyl)-4-thiophen-2-yl-6-(trifluoromethyl)pyrimidine	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	1.5910	uM
1-[(3-hydroxyphenyl)methyl]-5-[2-methylsulfonyl-6-(trifluoromethyl)pyrimidin-4-yl]pyridin-2-one	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	1.8210	uM
2-methylsulfonyl-4-phenyl-6-(trifluoromethyl)pyrimidine	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	2.2010	uM
4-(3-methylphenyl)-2-methylsulfonyl-6-(trifluoromethyl)pyrimidine	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	3.4870	uM
4-[[5-[2-methylsulfonyl-6-(trifluoromethyl)pyrimidin-4-yl]-2-oxo-1-pyridinyl]methyl]benzonitrile	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	3.4890	uM
methyl 3-[2-methylsulfonyl-6-(trifluoromethyl)pyrimidin-4-yl]benzoate	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	3.5160	uM
N-(2-hydroxy-5-methylphenyl)-4-[4-thiophen-2-yl-6-(trifluoromethyl)pyrimidin-2-yl]sulfonylbutanamide	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	4.0000	uM
3-[[5-[2-methylsulfonyl-6-(trifluoromethyl)pyrimidin-4-yl]-2-oxo-1-pyridinyl]methyl]benzonitrile	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	4.0600	uM
2-[(4-phenylphenyl)methylsulfonyl]-4-thiophen-2-yl-6-(trifluoromethyl)pyrimidine	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	4.2070	uM
1-[(3-ethynylphenyl)methyl]-5-[2-methylsulfonyl-6-(trifluoromethyl)pyrimidin-4-yl]pyridin-2-one	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	4.4770	uM
4-(4-methylphenyl)-2-methylsulfonyl-6-(trifluoromethyl)pyrimidine	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	6.3550	uM
4-(2-methylphenyl)-2-methylsulfonyl-6-(trifluoromethyl)pyrimidine	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	6.6420	uM
methyl 2-[2-methylsulfonyl-6-(trifluoromethyl)pyrimidin-4-yl]benzoate	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	7.0330	uM
2-methylsulfonyl-4-(3-phenoxyphenyl)-6-(trifluoromethyl)pyrimidine	1427662: Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	ec50	8.7560	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases abundance, affects cotreatment, increases methylation, decreases expression, increases expression (+1 more)	5
Acetaminophen	affects cotreatment, decreases expression	2
Aerosols	decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
1-Methyl-4-phenylpyridinium	decreases expression, increases reaction	2
Particulate Matter	decreases expression, increases abundance, increases expression, affects cotreatment	2
bisphenol F	increases expression	1
ginger extract	decreases reaction, increases abundance, increases expression	1
lasiocarpine	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression	1
lead acetate	decreases reaction, increases abundance, decreases expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment	1
plastochromanol 8	decreases expression	1
2,6-dichloro-4-nitrophenol	decreases expression	1
sodium arsenite	increases expression	1
2-bromopalmitate	increases abundance, increases palmitoylation, decreases reaction	1
nickel chloride	increases expression	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
S-1,2-dichlorovinyl-N-acetylcysteine	affects expression	1
demethoxycurcumin	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	increases expression	1
chloropicrin	increases expression	1
pyrimidifen	increases expression	1
bisphenol B	increases expression	1
olaparib	increases response to substance	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3994501	Binding	Inhibition of SDHB in human U2OS cells over-expressing Bim assessed as inhibition of apoptosis preincubated for 1 hr followed by doxycyclin addition to induce Bim protein expression measured after 24 hrs by Cell Titer-Glo assay	Discovery of Highly Potent 2-Sulfonyl-Pyrimidinyl Derivatives for Apoptosis Inhibition and Ischemia Treatment. — ACS Med Chem Lett

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 1 transformed cell line, 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B0YF	Abcam HEK293 SDHB KO	Transformed cell line	Female
CVCL_C6JR	hPheo1 KD-SDHB	Telomerase immortalized cell line	Female
CVCL_D1UB	Abcam U-87MG SDHB KO	Cancer cell line	Male
CVCL_D7ZZ	Ubigene A-549 SDHB KO	Cancer cell line	Male
CVCL_E0N8	Ubigene HeLa SDHB KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00414765	PHASE4	COMPLETED	Aldesleukin in Participants With Metastatic Renal Cell Carcinoma or Metastatic Melanoma
NCT00777504	PHASE4	UNKNOWN	Study to the Optimal Duration of Therapy With Oral Angiogenesis Inhibitors
NCT00930345	PHASE4	TERMINATED	Biological, Pathological and Imagery Markers in the First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma
NCT01206764	PHASE4	COMPLETED	A Trial of Everolimis in Patients With Advanced Renal Cell Carcinoma.
NCT01266837	PHASE4	COMPLETED	Open Label, Single Arm Trial to Characterize Patients With Metastatic RCC Treated With Everolimus After Failure of the First VEGF-targeted Therapy (MARC-2)
NCT02056587	PHASE4	COMPLETED	Everolimus in Patients With Metastatic Renal Cell Carcinoma Following Progression on Prior Bevacizumab Treatment
NCT02338570	PHASE4	TERMINATED	Outcome-related Factors in Patients With Metastatic Renal Cell Carcinoma Treated With Everolimus (ORCHIDEE)
NCT02596035	PHASE4	COMPLETED	An Investigational Immuno-therapy Safety Trial of Nivolumab in Patients With Advanced or Metastatic Renal Cell Carcinoma
NCT02982954	PHASE4	COMPLETED	A Study to Evaluate the Safety of Nivolumab and Ipilimumab in Subjects With Previously Untreated Advanced or Metastatic Renal Cell Cancer
NCT05949424	PHASE4	UNKNOWN	OPTI - DOSE: Optimal Dosing of Oral Anticancer Drugs in Older Adults
NCT07028125	PHASE4	RECRUITING	Digital Monitoring of Self-reported Symptoms by Patients Treated With Cabozantinib Plus Nivolumab for Advanced Clear-cell Renal Carcinoma
NCT07405086	PHASE4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT01379898	PHASE4	COMPLETED	Phenoxybenzamine Versus Doxazosin in PCC Patients
NCT01959711	PHASE4	COMPLETED	Randomized Clinical Trial of Posterior Retroperitoneoscopic Adrenalectomy Versus Lateral Laparoscopic Adrenalectomy
NCT05702944	PHASE4	RECRUITING	The Effect and Safety of Omitting Preoperative Alpha-adrenergic Blockade for Normotensive Pheochromocytoma
NCT00171977	PHASE4	COMPLETED	Post-Marketing Clinical Study of Postoperative Adjuvant Therapy With Imatinib Mesylate in Patients With Gastrointestinal Stromal Tumors (GIST)
NCT00510354	PHASE4	COMPLETED	Treatment of Patients With Everolimus and Imatinib Mesylate Who Have Progressive Gastro Intestinal Stromal Tumors (GIST) and Are Resistant to Imatinib Mesylate
NCT00756509	PHASE4	COMPLETED	Treatment of Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumors in First Line With Nilotinib
NCT02800330	PHASE4	COMPLETED	The Effects of the Proton Pump Inhibitor Esomeprazole on the Bioavailability of Regorafenib
NCT04825574	PHASE4	COMPLETED	Study for Patients Previously Treated in Avapritinib Clinical Trials
NCT00033904	PHASE3	COMPLETED	Survival Study Of Oncophage® vs. Observation In Patients With Kidney Cancer
NCT00126178	PHASE3	TERMINATED	Clinical Trial Studying a Personalized Cancer Vaccine in Patients With Non-metastatic Kidney Cancer
NCT00291369	PHASE3	COMPLETED	Cytokines in Patients With Metastatic Renal Cell Carcinoma of Intermediate Prognosis
NCT00410124	PHASE3	COMPLETED	RAD001 Plus Best Supportive Care (BSC) Versus BSC Plus Placebo in Patients With Metastatic Carcinoma of the Kidney Which Has Progressed After Treatment With Sorafenib and/or Sunitinib
NCT00474786	PHASE3	COMPLETED	Temsirolimus Versus Sorafenib As Second-Line Therapy In Patients With Advanced RCC Who Have Failed First-Line Sunitinib
NCT00478114	PHASE3	COMPLETED	Efficacy and Safety of Sorafenib in Advanced Renal Cell Carcinoma (RCC)
NCT00606632	PHASE3	COMPLETED	Pre-surgical Detection of Clear Cell Renal Cell Carcinoma (ccRCC) Using Radiolabeled G250-Antibody
NCT00606866	PHASE3	COMPLETED	MRI Study of BAY 43-9006 in Metastatic Renal Cell Carcinoma
NCT00631371	PHASE3	COMPLETED	Study Comparing Bevacizumab + Temsirolimus vs. Bevacizumab + Interferon-Alfa In Advanced Renal Cell Carcinoma Subjects
NCT00732914	PHASE3	COMPLETED	Sequential Study to Treat Renal Cell Carcinoma
NCT00869011	PHASE3	UNKNOWN	Exercise for Patients With Renal Cell Cancer Receiving Sunitinib
NCT00930033	PHASE3	COMPLETED	Clinical Trial to Assess the Importance of Nephrectomy
NCT01030783	PHASE3	COMPLETED	A Study to Compare Tivozanib (AV-951) to Sorafenib in Subjects With Advanced Renal Cell Carcinoma
NCT01076010	PHASE3	COMPLETED	An Extension Treatment Protocol for Subjects Who Have Participated in a Study of Tivozanib Versus Sorafenib in Kidney Carcinoma (Protocol AV-951-09-301).
NCT01198158	PHASE3	TERMINATED	Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy
NCT01223027	PHASE3	COMPLETED	Study of Dovitinib Versus Sorafenib in Patients With Metastatic Renal Cell Carcinoma
NCT01224288	PHASE3	ACTIVE_NOT_RECRUITING	Dynamic Contrast Enhancement Computed Tomography for Evaluating Tumor Perfusion in Patients With Metastatic Renal Cell Carcinoma Receiving Targeted Therapies: Renal Cell Carcinoma (RCC) Scramble
NCT01235962	PHASE3	COMPLETED	A Study to Evaluate Pazopanib as an Adjuvant Treatment for Localized Renal Cell Carcinoma (RCC)
NCT01265810	PHASE3	COMPLETED	Caphosol in Oral Mucositis Due to Targeted Therapy
NCT01265901	PHASE3	COMPLETED	IMA901 in Patients Receiving Sunitinib for Advanced/Metastatic Renal Cell Carcinoma