PIK3R2

Summary

PIK3R2 (phosphoinositide-3-kinase regulatory subunit 2, HGNC:8980) is a protein-coding gene on chromosome 19p13.11, encoding Phosphatidylinositol 3-kinase regulatory subunit beta (O00459). Regulatory subunit of phosphoinositide-3-kinase (PI3K), a kinase that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). In precision oncology, BRAF V600E AND PIK3R2 N561D is associated with resistance to Vemurafenib in Melanoma (CIViC Level D); 1 further curated variant–drug associations are listed below.

Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase that phosphorylates phosphatidylinositol and similar compounds, creating second messengers important in growth signaling pathways. PI3K functions as a heterodimer of a regulatory and a catalytic subunit. The protein encoded by this gene is a regulatory component of PI3K. Three transcript variants, one protein coding and the other two non-protein coding, have been found for this gene.

Source: NCBI Gene 5296 — RefSeq curated summary.

At a glance

• Gene–disease (curated): overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 504 total — 6 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 38
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_005027

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8980
Approved symbol	PIK3R2
Name	phosphoinositide-3-kinase regulatory subunit 2
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	P85B, p85, p85beta, p85-BETA
Ensembl gene	ENSG00000105647
Ensembl biotype	protein_coding
OMIM	603157
Entrez	5296

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 16 protein_coding, 5 nonsense_mediated_decay, 5 retained_intron

ENST00000222254, ENST00000426902, ENST00000459743, ENST00000464016, ENST00000474310, ENST00000600533, ENST00000617130, ENST00000617642, ENST00000672815, ENST00000674682, ENST00000675271, ENST00000874453, ENST00000874454, ENST00000874455, ENST00000874456, ENST00000874457, ENST00000874458, ENST00000874459, ENST00000925096, ENST00000925097, ENST00000925098, ENST00000925099, ENST00000925100, ENST00000925101, ENST00000965709, ENST00000965710

RefSeq mRNA: 1 — MANE Select: NM_005027 NM_005027

CCDS: CCDS12371

Canonical transcript exons

ENST00000222254 — 16 exons

Exon	Start	End
ENSE00000893034	18169087	18170532
ENSE00003067609	18153163	18153294
ENSE00003464305	18161966	18162051
ENSE00003474719	18155457	18156201
ENSE00003498129	18168726	18168896
ENSE00003498230	18161279	18161495
ENSE00003502685	18168475	18168546
ENSE00003506088	18166160	18166302
ENSE00003516250	18162202	18162310
ENSE00003540261	18162408	18162506
ENSE00003546729	18162967	18163147
ENSE00003571819	18163263	18163388
ENSE00003603229	18160471	18160563
ENSE00003645468	18160919	18160969
ENSE00003662245	18161054	18161185
ENSE00003704990	18167130	18167306

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 97.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.8949 / max 299.1967, expressed in 1804 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174596	33.7135	1800
174597	0.6441	383
174598	0.3111	63
174599	0.1761	56
174600	0.0501	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.66	gold quality
ganglionic eminence	UBERON:0004023	96.01	gold quality
stromal cell of endometrium	CL:0002255	95.80	gold quality
ventricular zone	UBERON:0003053	95.40	gold quality
right adrenal gland cortex	UBERON:0035827	93.75	gold quality
right adrenal gland	UBERON:0001233	93.11	gold quality
prefrontal cortex	UBERON:0000451	93.06	gold quality
Ammon’s horn	UBERON:0001954	92.83	gold quality
frontal cortex	UBERON:0001870	92.75	gold quality
frontal lobe	UBERON:0016525	92.75	gold quality
superior frontal gyrus	UBERON:0002661	92.65	gold quality
left adrenal gland	UBERON:0001234	92.38	gold quality
left adrenal gland cortex	UBERON:0035825	92.34	gold quality
right frontal lobe	UBERON:0002810	92.23	gold quality
cerebral cortex	UBERON:0000956	92.15	gold quality
nucleus accumbens	UBERON:0001882	92.00	gold quality
primary visual cortex	UBERON:0002436	91.91	gold quality
anterior cingulate cortex	UBERON:0009835	91.88	gold quality
temporal lobe	UBERON:0001871	91.77	gold quality
amygdala	UBERON:0001876	91.66	gold quality
adrenal gland	UBERON:0002369	91.12	gold quality
caudate nucleus	UBERON:0001873	90.99	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.77	gold quality
putamen	UBERON:0001874	90.70	gold quality
duodenum	UBERON:0002114	90.48	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.30	gold quality
brain	UBERON:0000955	90.18	gold quality
esophagus mucosa	UBERON:0002469	90.18	gold quality
pituitary gland	UBERON:0000007	89.65	gold quality
adenohypophysis	UBERON:0002196	89.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

76 targeting PIK3R2, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4307	99.82	70.45	3374

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• Mutant viruses carrying NS1 with mutations in SH3 binding motif 1 failed to interact with p85ss and induce the subsequent activation of PI3K/Akt pathway. (PMID:17881440)
• in VSMCs exposed to hyperglycemia, IGF-I stimulation of Shc facilitates the transfer of Grb2 to p85 resulting in enhanced PI3K activation and AKT phosphorylation leading to enhanced cell proliferation and migration (PMID:18420583)
• the influenza A virus NS1 protein interacts with the p85beta, but not the p85alpha, subunit of phosphatidylinositol 3-kinase (PMID:18534979)
• FGFR3 and p85 proteins interact in myeloma cells which express p85alpha and p85beta. (PMID:19286672)
• p85alpha and p85beta may recruit proteins in the endocytic machinery on Epo stimulation; mutated EpoRs from primary familial and congenital polycythemia patients lacking the 3 important tyrosines do not bind p85 or internalize on stimulation (PMID:19336760)
• PTEN-p85 association involves the unphosphorylated form of PTEN engaged within the PTEN-associated complex and also includes the p110beta isoform of PI3K. (PMID:19635806)
• Data show that mesothelin is a potential target in reducing resistance to cytotoxic drugs, and mesothelin-treated cells revealed rapid tyrosine phosphorylation of the p85 subunit of PI3K. (PMID:19747165)
• NS5A mediates activation of beta-catenin in a phosphoinositide-3 kinase-dependent fashion. (PMID:19846673)
• oncogenic p85 mutations lead to a loss of a C2-iSH2 domain contact that is required for inhibition of p110alpha by p85. (PMID:19915146)
• the PTEN phosphatase is active against the PI3K p85beta subunit and dephosphorylates a protein involved in insulin signaling where known downstream consequences are increased cell migration, motility, and invasion. (PMID:20515662)
• Macropinocytosis is regulated by interactions between Abi1 pY213 and the C-terminal SH2 domain of p85-thereby linking Abl kinase signaling to p85-dependent regulation of macropinocytosis. (PMID:20598684)
• Overexpression of SH3 domain of p85beta inhibits influenza A virus replication. (PMID:20653952)
• The crystal structure of human p85beta iSH2 determined to 3.3A resolution is reported. (PMID:21139197)
• miR-126 could target both VEGFA and PIK3R2, and its expression was decreased in human breast cancer, implying that miR-126 may play a role in tumor genesis and growth by regulating the VEGF/PI3K/AKT signaling pathway (PMID:21249429)
• study shows that p110beta nuclear localization signal and p85beta nuclear export sequence regulate p85beta/p110beta nuclear localization, supporting the idea that nuclear, but not cytoplasmic, p110beta controls cell survival (PMID:21383062)
• This paper reports the first purification of a phosphoinositide 3-kinase and shows that the protein is a heterodimer of an 85 kd regulatory subunit that mediates binding to phosphorylated proteins and a 110 kd catalytic subunit. (PMID:2174051)
• Multiple PIK3R1 and PIK3R2 mutations demonstrate gain of function, including disruption of a novel mechanism of pathway regulation wherein p85alpha dimers bind and stabilize PTEN. (PMID:21984976)
• recombinant production, crystallization and X-ray structure determination at 2.0 A resolution of the SH3 domain of human p85beta is described (PMID:22102226)
• identified mutations in AKT3, PIK3R2 and PIK3CA in 11 unrelated families with megalencephaly-capillary malformation and megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndromes (PMID:22729224)
• p85beta phosphoinositide 3-kinase subunit regulates tumor progression (PMID:22733740)
• miR-126-mediated phosphoinositide-3-kinase regulation, not only fine-tunes VEGF-signaling, but it strongly enhances the activities of Ang-1 on vessel stabilization and maturation. (PMID:22867989)
• Both alpha and beta isomers of the PI3K regulatory subunit p85 and full-length rotavirus NSP1 are important for this interaction, which results in efficient activation of the PI3K/Akt pathway during rotavirus infection. (PMID:23221569)
• Data indicate PI3K p85 mediates the interaction of beta-catenin with NF-kappaB (p65). (PMID:23583404)
• FBXL2 mediates the ubiquitylation and degradation of p85beta on cell membranes. (PMID:23604317)
• Study indicates that miR-126 is a tumor suppressor that inhibits gastric cancer cells proliferation by targeting PI3KR2, Crk and PLK2. (PMID:24969300)
• the metastasis and angiogenesis functions of miR-126-3p were mediated by LRP6 and PIK3R2. (PMID:25240815)
• The authors show that this potentiation involves reorganization of the natural CrkL-p85beta complex into a novel trimeric complex where influenza A virus NS1 serves as a bridging factor. (PMID:26099693)
• The miR-126 was found to act as proliferation suppressor targeting PIK3R2 gene and reducing p85beta (a regulatory subunit of PI3K kinase) protein translation and lower AKT kinase activity. (PMID:26384552)
• miR-3151 silencing by DNA methylation protected chronic lymphocytic leukemia cells from apoptosis by over-expression of its direct targets MADD and PIK3R2, constitutive activation of MEK/ERK and PI3K/AKT signaling , and over-expression of MCL1. (PMID:26517243)
• Constitutional and mosaic mutations in the PIK3R2 gene are associated with developmental brain disorders ranging from Bilateral perisylvian polymicrogyria with a normal head size to the megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome. (PMID:26520804)
• pik3r2 was confirmed to be a direct target of miR126 in prostate cancer. (PMID:26677064)
• indicated that miR-126 expression was negatively correlated with PIK3R2 mRNA expression (PMID:26723864)
• PIK3R2 D557H mutation causes polymicrogyria, corpus callosum hyperplasia and focal cortical dysplasia. (PMID:26860062)
• Data show that phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2) mRNA is a direct target of miR-126-3p. (PMID:27191494)
• Data indicate that miR-126 overexpression in RASFs inhibits PIK3R2 expression and promotes proliferation while inhibiting apoptosis. (PMID:27729613)
• this study shows that targeted depletion of PIK3R2 induces regression of lung squamous cell carcinoma (PMID:27835880)
• Data indicate that miR-126 expression negatively correlates with p85beta in CLL patients and that miR-126 can effectively target p85beta in a cell-line system. (PMID:28299881)
• Mosaic mutations in PIK3CA or PIK3R2 which activate class 1A PI3K cause severe non-ketotic hypoglycaemia in a subset of patients, with the metabolic phenotype presumably related to the extent of mosaicism within the liver (PMID:28566443)
• USP49 inhibits non-small cell lung cancer cell growth by suppressing PIK3R2/AKT signaling. (PMID:31001918)
• p85beta regulates autophagic degradation of AXL to activate oncogenic signaling. (PMID:32385243)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pik3r2	ENSDARG00000018060
mus_musculus	Pik3r2	ENSMUSG00000031834
rattus_norvegicus	Pik3r2	ENSRNOG00000019228
drosophila_melanogaster	Pi3K21B	FBGN0020622
caenorhabditis_elegans	aap-1	WBGENE00000001

Paralogs (2): PIK3R3 (ENSG00000117461), PIK3R1 (ENSG00000145675)

Protein

Protein identifiers

Phosphatidylinositol 3-kinase regulatory subunit beta — O00459 (reviewed: O00459)

Alternative names: Phosphatidylinositol 3-kinase 85 kDa regulatory subunit beta

All UniProt accessions (6): O00459, A0A087X257, A0A5F9ZHY3, A0A7I2U3A3, E9PFP1, V9GYJ4

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of phosphoinositide-3-kinase (PI3K), a kinase that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Binds to activated (phosphorylated) protein-tyrosine kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Indirectly regulates autophagy. Promotes nuclear translocation of XBP1 isoform 2 in a ER stress- and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement.

Subunit / interactions. Heterodimer of a regulatory subunit PIK3R2 and a p110 catalytic subunit (PIK3CA, PIK3CB or PIK3CD). Interacts with AXL. Interacts with FLT1 (tyrosine-phosphorylated) and FLT4 (tyrosine-phosphorylated). Interacts with NYAP1, NYAP2 and MYO16. Interacts with FBXL2; PIK3R2 is a substrate of the SCF(FBXL2) complex. Interacts with PTPN13; dephosphorylates PIK3R2. Interacts with XBP1 isoform 2; the interaction is direct and induces translocation of XBP1 isoform 2 into the nucleus in a ER stress- and/or insulin-dependent but PI3K-independent manner. Interacts with PIK3R1; the interaction is dissociated in an insulin-dependent manner. Interacts with SRC.

Post-translational modifications. Phosphorylated in response to signaling from activated receptor-type protein kinases. Dephosphorylated by PTPRJ. Dephosphorylated at Tyr-655 by PTPN13. Phosphorylation of Tyr-655 impairs while its dephosphorylation promotes interaction with FBXL2 and SCF(FBXL2)-mediated polyubiquitination. Ubiquitinated. Polyubiquitination by the SCF(FBXL2) complex probably promotes proteasomal degradation of PIK3R2.

Disease relevance. Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 (MPPH1) [MIM:603387] A syndrome characterized by megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The SH2 2 domain is required for interaction with FBXL2 and PTPN13.

Similarity. Belongs to the PI3K p85 subunit family.

RefSeq proteins (1): NP_005018* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000198	RhoGAP_dom	Domain
IPR000980	SH2	Domain
IPR001452	SH3_domain	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR032498	PI3K_P85_iSH2	Domain
IPR035020	PI3kinase_P85_cSH2	Domain
IPR035022	PI3kinase_P85_nSH2	Domain
IPR035586	PI3K_p85beta_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily

Pfam: PF00017, PF00620, PF16454

Enzyme classification (BRENDA):

• EC 2.7.1.137 — phosphatidylinositol 3-kinase (BRENDA: 29 organisms, 131 substrates, 146 inhibitors, 16 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.03–44	7
PHOSPHATIDYLINOSITOL	0.034–64	3
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE	0.004–15	2
PHOSPHATIDYLINOSITOL 4-PHOSPHATE	0.009–10	2
1,2-DIOCTANOYLPHOSPHATIDYLINOSITOL 4,5-DIPHOSPHA	0.05	1
PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE	0.011	1

UniProt features (59 total): helix 22, strand 11, sequence variant 6, domain 4, modified residue 3, mutagenesis site 3, turn 3, region of interest 3, compositionally biased region 2, chain 1, site 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
7RNU	X-RAY DIFFRACTION	1.45
3O5Z	X-RAY DIFFRACTION	2.01
2XS6	X-RAY DIFFRACTION	2.09
6OX7	X-RAY DIFFRACTION	2.75
6U28	X-RAY DIFFRACTION	2.95
7RCH	X-RAY DIFFRACTION	3.1
3MTT	X-RAY DIFFRACTION	3.3
2KT1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00459-F1	82.53	0.43

Functional residue map

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

Catalytic / active sites (1): 147 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Post-translational modifications (3): 464, 605, 655

Mutagenesis-validated functional residues (3):

Position	Phenotype
651	loss of interaction with fbxl2 and increased half-life; when associated with a-652.
652	loss of interaction with fbxl2 and increased half-life; when associated with a-651.
655	stabilized interaction with fbxl2 and decreased half-life.

Function

Pathways and Gene Ontology

Reactome pathways

48 pathways

ID	Pathway
R-HSA-109704	PI3K Cascade
R-HSA-112399	IRS-mediated signalling
R-HSA-114604	GPVI-mediated activation cascade
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1266695	Interleukin-7 signaling
R-HSA-1433557	Signaling by SCF-KIT
R-HSA-1660499	Synthesis of PIPs at the plasma membrane
R-HSA-186763	Downstream signal transduction
R-HSA-198203	PI3K/AKT activation
R-HSA-201556	Signaling by ALK
R-HSA-202424	Downstream TCR signaling
R-HSA-2029485	Role of phospholipids in phagocytosis
R-HSA-210993	Tie2 Signaling
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-2424491	DAP12 signaling
R-HSA-2730905	Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-373753	Nephrin family interactions
R-HSA-389357	CD28 dependent PI3K/Akt signaling
R-HSA-416476	G alpha (q) signalling events
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8853659	RET signaling
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle

MSigDB gene sets: 550 (showing top): REACTOME_INTERLEUKIN_2_FAMILY_SIGNALING, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_YELLOW_DN, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_B_CELL_ACTIVATION, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT

GO Biological Process (18): intracellular glucose homeostasis (GO:0001678), immune response (GO:0006955), insulin receptor signaling pathway (GO:0008286), regulation of autophagy (GO:0010506), protein transport (GO:0015031), B cell differentiation (GO:0030183), T cell differentiation (GO:0030217), regulation of actin filament polymerization (GO:0030833), cellular response to insulin stimulus (GO:0032869), response to endoplasmic reticulum stress (GO:0034976), positive regulation of protein import into nucleus (GO:0042307), negative regulation of MAPK cascade (GO:0043409), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), positive regulation of cell adhesion (GO:0045785), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of stress fiber assembly (GO:0051492), regulation of protein localization to plasma membrane (GO:1903076), signal transduction (GO:0007165)

GO Molecular Function (8): phosphotyrosine residue binding (GO:0001784), GTPase activator activity (GO:0005096), protein phosphatase binding (GO:0019903), receptor tyrosine kinase binding (GO:0030971), phosphatidylinositol 3-kinase regulatory subunit binding (GO:0036312), 1-phosphatidylinositol-3-kinase regulator activity (GO:0046935), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), cytosol (GO:0005829), focal adhesion (GO:0005925), phosphatidylinositol 3-kinase complex, class IA (GO:0005943)

Reactome top-level categories

Rollup of top-20 pathways:

Category	Pathways
Signaling by Receptor Tyrosine Kinases	2
IRS-mediated signalling	1
IRS-related events triggered by IGF1R	1
Insulin receptor signalling cascade	1
Platelet activation, signaling and aggregation	1
Intracellular signaling by second messengers	1
Signaling by Interleukins	1
PI Metabolism	1
Signaling by PDGF	1
Signaling by NTRK1 (TRKA)	1
TCR signaling	1
Fcgamma receptor (FCGR) dependent phagocytosis	1
Cell surface interactions at the vascular wall	1
PI3K/AKT Signaling in Cancer	1
DAP12 interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lymphocyte differentiation	2
glucose homeostasis	1
intracellular chemical homeostasis	1
immune system process	1
response to stimulus	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
autophagy	1
regulation of catabolic process	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
B cell activation	1
T cell activation	1
regulation of actin polymerization or depolymerization	1
actin filament polymerization	1
regulation of protein polymerization	1
response to insulin	1
cellular response to peptide hormone stimulus	1
cellular response to stress	1
protein import into nucleus	1
regulation of protein import into nucleus	1
positive regulation of nucleocytoplasmic transport	1
positive regulation of intracellular protein transport	1
positive regulation of protein localization to nucleus	1
MAPK cascade	1
regulation of MAPK cascade	1
negative regulation of intracellular signal transduction	1
intracellular signaling cassette	1
cell adhesion	1
regulation of cell adhesion	1
positive regulation of cellular process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of actomyosin structure organization	1
protein localization to plasma membrane	1
regulation of protein localization to cell periphery	1

Protein interactions and networks

STRING

1974 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIK3R2	PIK3CD	O00329	997
PIK3R2	PIK3CA	P42336	997
PIK3R2	PIK3CB	P42338	997
PIK3R2	PIK3CG	P48736	991
PIK3R2	PIK3R1	P27986	959
PIK3R2	PIK3R3	Q92569	957
PIK3R2	XBP1	P17861	936
PIK3R2	FBXL2	Q9UKC9	829
PIK3R2	PIK3R5	Q8WYR1	817
PIK3R2	IRS1	P35568	807
PIK3R2	PTEN	P60484	807
PIK3R2	SPRED1	Q7Z699	805
PIK3R2	IRS2	Q9Y4H2	771
PIK3R2	USP8	P40818	746
PIK3R2	CDC42	P21181	719

IntAct

433 interactions, top by confidence:

A	B	Type	Score
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
PIK3CA	PIK3R2	psi-mi:“MI:0915”(physical association)	0.900

BioGRID (344): PIK3R2 (Reconstituted Complex), YWHAQ (Affinity Capture-Western), PIK3R2 (Affinity Capture-Western), PIK3R2 (Two-hybrid), PIK3R2 (Two-hybrid), PIK3R2 (Two-hybrid), KRT38 (Two-hybrid), IKZF3 (Two-hybrid), KRT20 (Two-hybrid), RINT1 (Two-hybrid), MRFAP1L1 (Two-hybrid), DYDC1 (Two-hybrid), PIK3R2 (Affinity Capture-RNA), PIK3R2 (Affinity Capture-RNA), PIK3R2 (Two-hybrid)

ESM2 similar proteins: A1A4I4, A4K436, A6QLH6, D3ZVM4, F1M5F3, F1N2W9, O00459, O08908, O43272, O60336, O95294, P0C928, P23726, P70268, Q0VGM9, Q16512, Q1JQD7, Q1PSW8, Q3KRC5, Q496Y0, Q5M9F8, Q5R812, Q5RE34, Q5RJZ1, Q5RKZ7, Q5XIS9, Q5ZIW1, Q63433, Q63788, Q6H1L8, Q6NS57, Q6NYU2, Q6PFQ7, Q8BZ03, Q8R1T1, Q91XI1, Q920N2, Q92889, Q92994, Q96G46

Diamond homologs: G5ECJ6, O00459, O08908, O14508, O14544, O35717, O46404, O88582, P00519, P00520, P00521, P10447, P14234, P15498, P23726, P23727, P26450, P27986, P41242, P41243, P42679, P42684, P54100, P62993, P62994, Q08012, Q08DN7, Q45FX5, Q4JIM5, Q54RB7, Q5R4J7, Q5R685, Q5RCM6, Q60631, Q62662, Q63787, Q63788, Q63789, Q64143, Q6P6U0

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
CBL	down-regulates	PIK3R2	ubiquitination
ESR1	up-regulates	PIK3R2	binding
TGFBR2	up-regulates	PIK3R2	binding
TGFBR1	up-regulates	PIK3R2	binding
LAT	“up-regulates activity”	PIK3R2	binding
CBLB	“down-regulates activity”	PIK3R2	ubiquitination
FBXO2	“down-regulates quantity by destabilization”	PIK3R2	binding
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	PIK3R2	polyubiquitination
FBXL2	“down-regulates quantity by destabilization”	PIK3R2	binding
“Cullin 3-RBX1-Skp1”	“down-regulates quantity by destabilization”	PIK3R2	polyubiquitination
has-mir-126-3p	“down-regulates quantity by repression”	PIK3R2	“post transcriptional regulation”
EPHA2	up-regulates	PIK3R2

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 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
Constitutive Signaling by EGFRvIII	6	58.7×	1e-08
Signaling by ERBB2 ECD mutants	6	55.2×	2e-08
Signaling by ALK	7	54.8×	1e-09
Regulation of signaling by CBL	7	47.6×	3e-09
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	6	46.9×	6e-08
PI3K events in ERBB2 signaling	5	46.0×	1e-06
Interleukin receptor SHC signaling	8	44.7×	4e-10
Interleukin-2 family signaling	5	43.5×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	10	51.4×	1e-12
ephrin receptor signaling pathway	9	37.8×	4e-10
cell surface receptor protein tyrosine kinase signaling pathway	16	33.9×	1e-17
regulation of GTPase activity	5	31.1×	3e-05
insulin-like growth factor receptor signaling pathway	5	30.2×	4e-05
phosphatidylinositol 3-kinase/protein kinase B signal transduction	10	25.7×	9e-10
protein autophosphorylation	12	21.3×	1e-10
positive regulation of protein localization to plasma membrane	6	19.9×	3e-05

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	6
Uncertain significance	213
Likely benign	174
Benign	59

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
143990	NM_005027.4(PIK3R2):c.1202T>C (p.Leu401Pro)	Pathogenic
280374	NM_005027.4(PIK3R2):c.1126A>G (p.Lys376Glu)	Pathogenic
280388	NM_005027.4(PIK3R2):c.1690A>G (p.Lys564Glu)	Pathogenic
39808	NM_005027.4(PIK3R2):c.1117G>A (p.Gly373Arg)	Pathogenic
424553	NM_005027.4(PIK3R2):c.1669G>C (p.Asp557His)	Pathogenic
995384	NM_005027.4(PIK3R2):c.1153G>A (p.Gly385Arg)	Pathogenic
376165	NM_005027.4(PIK3R2):c.1681A>G (p.Asn561Asp)	Likely pathogenic
431911	NM_005027.4(PIK3R2):c.1948A>G (p.Ser650Gly)	Likely pathogenic
620407	NM_005027.4(PIK3R2):c.1359C>A (p.Tyr453Ter)	Likely pathogenic
625283	NM_005027.4(PIK3R2):c.1056C>G (p.Phe352Leu)	Likely pathogenic
800333	NM_005027.4(PIK3R2):c.850G>A (p.Val284Met)	Likely pathogenic
976716	NM_005027.4(PIK3R2):c.988T>G (p.Trp330Gly)	Likely pathogenic

SpliceAI

2083 predictions. Top by Δscore:

Variant	Effect	Δscore
19:18153291:CCAGG:C	donor_loss	1.0000
19:18153292:CAGG:C	donor_loss	1.0000
19:18153292:CAGGT:C	donor_loss	1.0000
19:18153293:AGGTG:A	donor_loss	1.0000
19:18153294:GGT:G	donor_loss	1.0000
19:18153295:G:GG	donor_gain	1.0000
19:18153295:GTG:G	donor_loss	1.0000
19:18160467:CCA:C	acceptor_loss	1.0000
19:18160468:CA:C	acceptor_loss	1.0000
19:18160468:CAGGC:C	acceptor_loss	1.0000
19:18160469:A:AC	acceptor_loss	1.0000
19:18160469:A:AG	acceptor_gain	1.0000
19:18160469:AGGCC:A	acceptor_loss	1.0000
19:18160470:G:GA	acceptor_gain	1.0000
19:18160470:GGCCT:G	acceptor_gain	1.0000
19:18160559:GACAG:G	donor_gain	1.0000
19:18160561:CAGG:C	donor_loss	1.0000
19:18160561:CAGGT:C	donor_loss	1.0000
19:18160562:AGG:A	donor_loss	1.0000
19:18160562:AGGT:A	donor_loss	1.0000
19:18160563:GGTA:G	donor_loss	1.0000
19:18160564:G:GA	donor_loss	1.0000
19:18160564:G:GG	donor_gain	1.0000
19:18160565:T:A	donor_loss	1.0000
19:18160914:CCCA:C	acceptor_loss	1.0000
19:18160915:CCAG:C	acceptor_loss	1.0000
19:18160916:CAG:C	acceptor_loss	1.0000
19:18160917:A:AC	acceptor_loss	1.0000
19:18160917:AG:A	acceptor_gain	1.0000
19:18160917:AGGGC:A	acceptor_loss	1.0000

AlphaMissense

4685 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:18162288:T:A	W330R	1.000
19:18162288:T:C	W330R	1.000
19:18162290:G:C	W330C	1.000
19:18162290:G:T	W330C	1.000
19:18162291:T:C	Y331H	1.000
19:18162291:T:G	Y331D	1.000
19:18162292:A:C	Y331S	1.000
19:18162294:T:A	W332R	1.000
19:18162294:T:C	W332R	1.000
19:18162296:G:C	W332C	1.000
19:18162296:G:T	W332C	1.000
19:18162297:G:T	G333W	1.000
19:18162298:G:T	G333V	1.000
19:18162310:G:C	R337T	1.000
19:18162310:G:T	R337M	1.000
19:18162408:G:C	R337S	1.000
19:18162408:G:T	R337S	1.000
19:18162415:G:C	V340L	1.000
19:18162415:G:T	V340L	1.000
19:18162428:T:A	L344H	1.000
19:18162428:T:C	L344P	1.000
19:18162442:G:C	D349H	1.000
19:18162445:G:C	G350R	1.000
19:18162446:G:A	G350D	1.000
19:18162446:G:T	G350V	1.000
19:18162451:T:A	F352I	1.000
19:18162451:T:C	F352L	1.000
19:18162452:T:C	F352S	1.000
19:18162453:C:A	F352L	1.000
19:18162453:C:G	F352L	1.000

dbSNP variants (sampled 300 via entrez): RS1000078158 (19:18162131 G>A,T), RS1000165677 (19:18168928 G>A,C,T), RS1000383143 (19:18164421 C>T), RS1000501259 (19:18167653 T>C), RS1000647049 (19:18154736 C>T), RS1000817045 (19:18153794 C>G), RS1001083070 (19:18160720 C>T), RS1001167635 (19:18165022 G>A,C), RS1001210335 (19:18155706 A>G), RS1001339002 (19:18170149 A>C), RS1001560942 (19:18168019 C>G), RS1001591816 (19:18168297 G>A,C,T), RS1001791278 (19:18161571 C>A,T), RS1001899727 (19:18166733 G>A), RS1001932256 (19:18167054 T>C)

Disease associations

OMIM: gene MIM:603157 | disease phenotypes: MIM:603387, MIM:602501, MIM:254500

GenCC curated gene-disease

Disease	Classification	Inheritance
overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes	Definitive	Autosomal dominant
megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1	Definitive	Autosomal dominant
megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes	Definitive	AD

Mondo (7): megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome (MONDO:0019375), megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 (MONDO:0011313), overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes (MONDO:0100283), overgrowth syndrome (MONDO:0019716), intellectual disability (MONDO:0001071), megalencephaly-capillary malformation-polymicrogyria syndrome (MONDO:0011240), plasma cell myeloma (MONDO:0009693)

Orphanet (6): Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome (Orphanet:83473), Overgrowth syndrome (Orphanet:93460), Megalencephaly-capillary malformation-polymicrogyria syndrome (Orphanet:60040), Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

38 total (30 of 38 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000160	Narrow mouth
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000316	Hypertelorism
HP:0000348	High forehead
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000618	Blindness
HP:0000637	Long palpebral fissure
HP:0001090	Abnormally large globe
HP:0001162	Postaxial hand polydactyly
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001302	Pachygyria
HP:0001355	Megalencephaly
HP:0001548	Overgrowth
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001653	Mitral regurgitation
HP:0001671	Abnormal cardiac septum morphology
HP:0002007	Frontal bossing
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002126	Polymicrogyria
HP:0002187	Profound intellectual disability
HP:0002808	Kyphosis
HP:0002943	Thoracic scoliosis
HP:0003202	Skeletal muscle atrophy
HP:0005105	Abnormal nasal morphology

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST008550_10	Mental health study participation (completed survey)	1.000000e-10
GCST008550_11	Mental health study participation (completed survey)	3.000000e-08
GCST008550_34	Mental health study participation (completed survey)	2.000000e-09
GCST90002379_196	Basophil count	4.000000e-13
GCST90002380_12	Basophil percentage of white cells	4.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0010130	health study participation
EFO:0005090	basophil count
EFO:0007992	basophil percentage of leukocytes

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009101	Multiple Myeloma	C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650
C566381	Megalancephaly Polymicrogyria-Polydactyly Hydrocephalus Syndrome (supp.)
C536142	Megalencephaly cutis marmorata telangiectatica congenita (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3559703 (PROTEIN COMPLEX GROUP), CHEMBL3885615 (PROTEIN COMPLEX), CHEMBL4437 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 20,664 (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
CHEMBL2216870	IDELALISIB	4	10,163
CHEMBL4650215	INAVOLISIB	4	876
CHEMBL2387080	TASELISIB	3	3,473
CHEMBL3683575	ROGINOLISIB	2	67
CHEMBL4438249	AMDIZALISIB	2	14
CHEMBL521851	PICTILISIB	2	6,071

Clinical evidence (CIViC)

Drug × variant × indication: 2 predictive associations from 2 curated evidence items; also 1 functional.

Variant	Therapy	Indication	Effect	Level	CIViC
BRAF V600E AND PIK3R2 N561D	Vemurafenib	Melanoma	Resistance	CIViC D	EID4783
PIK3R2 Overexpression	Vemurafenib	Melanoma	Resistance	CIViC D	EID6266

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

PharmGKB clinical annotations

13 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs117341846	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs117951771	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs118129530	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs138602176	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs145623321	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs148013902	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs148235907	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs150688309	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs55633228	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs56022120	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs58695150	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs79430272	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs8110364	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs8110364	PIK3R2	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil
rs58695150	MAST3, PIK3R2	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Phosphatidylinositol kinases

Binding affinities (BindingDB)

840 measured of 1478 human assays (1478 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Inavolisib	KI	0.034 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
(2S)-2-[[2-[(4S)-4-(fluoromethyl)-2-oxo-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]propanamide	KI	0.04 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
(2S)-2-[[2-[(4S)-4-(difluoromethyl)-2-oxo-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]butanamide	KI	0.048 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
(2S)-2-cyclopropyl-2-[[2-[(4S)-4-(fluoromethyl)-2-oxo-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]acetamide	KI	0.051 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
(2S)-2-cyclopropyl-2-[[2-[(4S)-4-(difluoromethyl)-2-oxo-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]acetamide	KI	0.06 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
Taselisib	KI	0.09 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
(2S)-2-cyclopropyl-2-[[2-[(4R)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]acetamide	KI	0.464 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
(2S)-2-cyclobutyl-2-[[2-[(4R)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]acetamide	KI	0.949 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
4-amino-6-[[(1S)-1-[3-chloro-6-(4-hydroxyphenyl)imidazo[1,2-b]pyridazin-7-yl]ethyl]amino]pyrimidine-5-carbonitrile	IC50	1 nM	US-10208066: Imidazopyridazine compounds and their use
4-[3-(5,8-dichloroquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]pyridine-2-carbonitrile	IC50	1 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[[(1S)-1-(3-chloro-6-phenylimidazo[1,2-b]pyridazin-7-yl)ethyl]amino]-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile	IC50	2 nM	US-10208066: Imidazopyridazine compounds and their use
4-[3-(8-chloro-5-fluoroquinolin-4-yl)-2-methyl-7-(1,3-thiazol-2-yl)benzimidazol-5-yl]morpholine	IC50	2 nM	US-10214519
4-[3-(8-chloroquinolin-4-yl)-7-(1H-imidazol-5-yl)benzimidazol-5-yl]morpholine	IC50	2 nM	US-10214519
4-[3-(8-chloroquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]morpholine	IC50	2 nM	US-10214519
4-[3-(5,8-difluoroquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]pyridine-2-carbonitrile	IC50	2 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(8-chloroquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]-3-fluoropyridin-2-amine	IC50	2 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(8-chloro-5-fluoroquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]-3-fluoropyridin-2-amine	IC50	2 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(5,8-difluoroquinolin-4-yl)-2-ethyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]-3-fluoropyridin-2-amine	IC50	2 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(5-fluoroquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]pyridine-2-carbonitrile	IC50	2 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
5,8-difluoro-4-[6-(2-fluoro-4-pyridinyl)-2-methyl-4-(1H-1,2,4-triazol-5-yl)benzimidazol-1-yl]quinoline	IC50	2 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
N-[(1S)-1-[3-chloro-6-(2-fluorophenyl)imidazo[1,2-b]pyridazin-7-yl]ethyl]-7H-purin-6-amine	IC50	3 nM	US-10208066: Imidazopyridazine compounds and their use
4-[3-(5,8-difluoroquinolin-4-yl)-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]morpholine	IC50	3 nM	US-10214519
4-[3-(8-chloroquinolin-4-yl)-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]morpholine	IC50	3 nM	US-10214519
4-[3-(8-chloroquinolin-4-yl)-7-(1,3-oxazol-2-yl)benzimidazol-5-yl]morpholine	IC50	3 nM	US-10214519
1-(8-chloro-5-fluoroquinolin-4-yl)-2-methyl-6-pyridin-4-ylbenzimidazole-4-carboxamide	IC50	3 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(8-chloro-5-fluoroquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]pyridin-2-amine	IC50	3 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(8-chloro-5-fluoroquinolin-4-yl)-2-cyclopropyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]-3-fluoropyridin-2-amine	IC50	3 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(8-chloro-3-methylquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]-3-fluoropyridin-2-amine	IC50	3 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(5,7-difluoroquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]pyridine-2-carbonitrile	IC50	3 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(8-chloroquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]pyridine-2-carbonitrile	IC50	3 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(8-chloroquinolin-4-yl)-2-propyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]morpholine	IC50	4 nM	US-10214519
4-[3-[8-chloro-2-(difluoromethyl)quinolin-4-yl]-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]morpholine	IC50	4 nM	US-10214519
4-[3-(8-chloro-5-fluoroquinolin-4-yl)-2-methyl-7-(4-methyl-1,3-thiazol-2-yl)benzimidazol-5-yl]morpholine	IC50	4 nM	US-10214519
4-[7-(2-chloro-1H-imidazol-5-yl)-3-(8-chloroquinolin-4-yl)-2-methylbenzimidazol-5-yl]morpholine	IC50	4 nM	US-10214519
4-[7-(2-chloro-1H-imidazol-5-yl)-3-(8-chloroquinolin-4-yl)benzimidazol-5-yl]morpholine	IC50	4 nM	US-10214519
8-chloro-5-fluoro-4-[2-methyl-6-pyridin-4-yl-4-(1H-1,2,4-triazol-5-yl)benzimidazol-1-yl]quinoline	IC50	4 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(8-chloro-5-fluoroquinolin-4-yl)-2-propyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]-3-fluoropyridin-2-amine	IC50	4 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(5,8-dichloroquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]-3-fluoropyridin-2-amine	IC50	4 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(8-chloroquinolin-4-yl)-2-ethyl-7-(1,3-oxazol-2-yl)benzimidazol-5-yl]morpholine	IC50	5 nM	US-10214519
4-[3-(5,8-difluoroquinolin-4-yl)-2-methyl-7-(1,3-oxazol-2-yl)benzimidazol-5-yl]morpholine	IC50	5 nM	US-10214519
4-[3-(5,8-difluoroquinolin-4-yl)-7-(1,3-oxazol-2-yl)-2-propylbenzimidazol-5-yl]morpholine	IC50	5 nM	US-10214519
4-[3-(5,8-difluoroquinolin-4-yl)-7-(1,3-oxazol-2-yl)benzimidazol-5-yl]morpholine	IC50	5 nM	US-10214519
4-[3-(8-chloro-5-fluoroquinolin-4-yl)-7-(2-chloro-1H-imidazol-5-yl)-2-methylbenzimidazol-5-yl]morpholine	IC50	5 nM	US-10214519
4-[3-(5,8-dichloro-2-methylquinolin-4-yl)-7-(1H-imidazol-5-yl)benzimidazol-5-yl]morpholine	IC50	5 nM	US-10214519
4-[3-(5,8-difluoroquinolin-4-yl)-7-(1H-imidazol-5-yl)benzimidazol-5-yl]morpholine	IC50	5 nM	US-10214519
8-chloro-4-[6-pyridin-4-yl-4-(1H-1,2,4-triazol-5-yl)benzimidazol-1-yl]quinoline	IC50	5 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
8-chloro-4-[2-methyl-6-(2-methyl-4-pyridinyl)-4-(1H-1,2,4-triazol-5-yl)benzimidazol-1-yl]quinoline	IC50	5 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(5,8-difluoroquinolin-4-yl)-2-propyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]-3-fluoropyridin-2-amine	IC50	5 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
3-fluoro-4-[3-(5-fluoroquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]pyridin-2-amine	IC50	5 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(8-fluoroquinolin-4-yl)-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]morpholine	IC50	6 nM	US-10214519

ChEMBL bioactivities

1321 potent at pChembl≥5 of 1461 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL6002533
9.00	IC50	1	nM	CHEMBL5924262
9.00	IC50	1	nM	CHEMBL5916761
8.70	IC50	2	nM	CHEMBL5888916
8.70	IC50	2	nM	CHEMBL6033360
8.70	IC50	2	nM	CHEMBL5880970
8.70	IC50	2	nM	CHEMBL5902751
8.70	IC50	2	nM	CHEMBL5774157
8.70	IC50	2	nM	CHEMBL5957032
8.70	IC50	2	nM	CHEMBL4647791
8.70	IC50	2	nM	CHEMBL5818660
8.70	IC50	2	nM	CHEMBL5998780
8.70	IC50	2	nM	CHEMBL5924262
8.70	IC50	2	nM	CHEMBL5744071
8.52	IC50	3	nM	CHEMBL5769598
8.52	IC50	3	nM	CHEMBL4646376
8.52	IC50	3	nM	CHEMBL5897720
8.52	IC50	3	nM	CHEMBL5800580
8.52	IC50	3	nM	CHEMBL5964102
8.52	IC50	3	nM	CHEMBL4470860
8.52	IC50	3	nM	CHEMBL5921395
8.52	IC50	3	nM	CHEMBL5789334
8.52	IC50	3	nM	CHEMBL5993540
8.52	IC50	3	nM	CHEMBL5941074
8.40	IC50	4	nM	CHEMBL5789071
8.40	IC50	4	nM	CHEMBL5907233
8.40	IC50	4	nM	CHEMBL5780564
8.40	IC50	4	nM	CHEMBL5838167
8.40	IC50	4	nM	CHEMBL5999580
8.40	IC50	4	nM	CHEMBL5856108
8.40	IC50	4	nM	CHEMBL4647791
8.40	IC50	4	nM	CHEMBL5820221
8.40	IC50	4	nM	CHEMBL5756370
8.40	IC50	4	nM	CHEMBL5772820
8.40	IC50	4	nM	CHEMBL5961627
8.40	IC50	4	nM	CHEMBL5818660
8.40	IC50	4	nM	CHEMBL5941074
8.40	IC50	4	nM	CHEMBL5861950
8.40	IC50	4	nM	CHEMBL5816408
8.40	IC50	4	nM	CHEMBL5781665
8.40	IC50	4	nM	CHEMBL5888776
8.40	IC50	4	nM	CHEMBL5780265
8.30	IC50	5	nM	CHEMBL5771672
8.30	IC50	5	nM	CHEMBL5918117
8.30	IC50	5	nM	CHEMBL5853060
8.30	IC50	5	nM	CHEMBL5787062
8.30	IC50	5	nM	CHEMBL5849419
8.30	IC50	5	nM	CHEMBL5852093
8.30	IC50	5	nM	CHEMBL5957592
8.30	IC50	5	nM	CHEMBL5788149

PubChem BioAssay actives

7 with measured affinity, of 11 total; 6 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
[(1S,6Z,9S,9aS,10R,11aS)-6-[[3-(dimethylamino)propyl-methylamino]methylidene]-1-hydroxy-9-(methoxymethyl)-9a,11a-dimethyl-4,5,7-trioxo-1,2,3,3a,5a,9,10,11-octahydroindeno[4,5-h]isochromen-10-yl] acetate	1798030: PI3K Inhibition Assay from Article 10.1021/jm7012858: “Synthesis and structure-activity relationships of ring-opened 17-hydroxywortmannins: potent phosphoinositide 3-kinase inhibitors with improved properties and anticancer efficacy.”	ic50	0.0110	uM
2,4-diamino-6-[(6S)-6-(5-chloro-4-oxo-3-phenylquinazolin-2-yl)-5-azaspiro[2.4]heptan-5-yl]pyrimidine-5-carbonitrile	1690218: Inhibition of human full-length recombinant His-tagged PI3K p110beta/p85beta expressed in baculovirus expression system using PIP2 as substrate measured after 2 hrs by ADP-Glo luminescence assay	ic50	0.1740	uM
4-[5-amino-6-(cyclopropanecarbonyl)pyrazin-2-yl]-N-(4-hydroxycyclohexyl)-3-methylbenzenesulfonamide	2066708: Inhibition of P13Kbeta (unknown origin) in the presence of ATP by scintillation proximity assay	ic50	0.4000	uM
N-[5-[4-[5-[[(2S,6R)-2,6-dimethylmorpholin-4-yl]methyl]-1,3-oxazol-2-yl]-1H-indazol-6-yl]-2-methoxy-3-pyridinyl]methanesulfonamide	1894037: Inhibition of human PI3K beta	ic50	0.6300	uM
4-[6-amino-5-(2-methyl-1,3-oxazol-5-yl)-3-pyridinyl]-N-(2-hydroxy-2-methylpropyl)-3-methylbenzenesulfonamide	2066708: Inhibition of P13Kbeta (unknown origin) in the presence of ATP by scintillation proximity assay	ic50	1.7000	uM
5-chloro-3-phenyl-2-[(6S)-5-(7H-purin-6-yl)-5-azaspiro[2.4]heptan-6-yl]quinazolin-4-one	1690218: Inhibition of human full-length recombinant His-tagged PI3K p110beta/p85beta expressed in baculovirus expression system using PIP2 as substrate measured after 2 hrs by ADP-Glo luminescence assay	ic50	2.6410	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, increases expression	3
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression, increases expression	3
bisphenol A	decreases expression, decreases methylation	2
Estradiol	decreases expression	2
Oxygen	affects cotreatment, decreases phosphorylation, decreases reaction, decreases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, decreases expression	2
Smoke	increases abundance, increases expression, decreases expression	2
Valproic Acid	increases methylation, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
nuciferine	affects cotreatment, decreases phosphorylation, decreases reaction	1
beta-lapachone	increases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
aflatoxin B2	increases methylation	1
muconaldehyde	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
antimonite	decreases expression, increases abundance	1
chloropicrin	decreases expression	1
monomethylarsonous acid	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	affects cotreatment, increases expression	1

ChEMBL screening assays

27 unique, capped per target: 27 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3706369	Binding	Binding Assay: The efficacy of compounds of the invention in inhibiting the PI3K induced-lipid phosphorylation may be tested in the following binding assay. The assay combines the scintillation proximity assay technology (SPA, Amersham) wit	Tricyclic pyrazol amine derivatives

Cellosaurus cell lines

18 cell lines: 9 cancer cell line, 7 induced pluripotent stem cell, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3DV	Abcam HEK293T PIK3R2 KO	Transformed cell line	Female
CVCL_B8ML	Abcam HCT 116 PIK3R2 KO	Cancer cell line	Male
CVCL_B9AC	Abcam MCF-7 PIK3R2 KO	Cancer cell line	Female
CVCL_B9PT	Abcam A-549 PIK3R2 KO	Cancer cell line	Male
CVCL_D0WN	HPS2936	Induced pluripotent stem cell	Female
CVCL_D0WP	HPS2937	Induced pluripotent stem cell	Female
CVCL_D0WQ	HPS2938	Induced pluripotent stem cell	Female
CVCL_D0WR	HPS2939	Induced pluripotent stem cell	Female
CVCL_D0WS	HPS2940	Induced pluripotent stem cell	Female
CVCL_D0WT	HPS2941	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00104104	PHASE4	COMPLETED	A Multiple Myeloma Trial in Patients With Bone Metastases
NCT00211211	PHASE4	COMPLETED	FREE Study - Fracture Reduction Evaluation
NCT00242528	PHASE4	WITHDRAWN	Open-label Study, to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Bone Lesions Secondary to Multiple Myeloma.
NCT00257114	PHASE4	COMPLETED	Evaluation of VELCADE Given as Retreatment to Multiple Myeloma Patients for Efficacy, Safety and Tolerability
NCT00352703	PHASE4	COMPLETED	PROMPT - Palifermin in Reduction of Oral Mucositis in PBSC Transplantation
NCT00361140	PHASE4	COMPLETED	Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)
NCT00622505	PHASE4	COMPLETED	Zoledronic Acid Treatment (Every 4 or 12 Weeks) to Prevent Skeletal Complications in Advanced Multiple Myeloma Participants
NCT00652041	PHASE4	COMPLETED	Bortezomib/Adriamycine/Melfalan/Prednisone (VAMP)/Thalidomide/Cyclophosphamide/Dexamethasone (TaCyDex) or Bortezomib/Melfalan/Prednisone (V-MP)/TaCyDex) in Refractary or Relapsed Multiple Myeloma
NCT00733538	PHASE4	COMPLETED	Stage I Multiple Myeloma Treatment
NCT01087008	PHASE4	COMPLETED	Zoledronic Acid in Patients With Multiple Myeloma and Asymptomatic Biochemical Relapse
NCT01249690	PHASE4	UNKNOWN	Efficacy Study of PAD and TAD in Newly Diagnosed Multiple Myeloma
NCT01410929	PHASE4	WITHDRAWN	Evaluation of Vertebral Compression Fracture Fixation With RF Kyphoplasty in Patients With Multiple Myeloma
NCT01731886	PHASE4	COMPLETED	Lenalidomide and Dexamethasone With/Without Stem Cell Transplant in Patients With Multiple Myeloma
NCT01868828	PHASE4	UNKNOWN	A Study of PAD Versus Velcade, Cyclophosphamide and Dexamethasone (VCD) Treatment in Subjects With Multiple Myeloma
NCT02268890	PHASE4	COMPLETED	A Pharmacokinetic Study of Bortezomib in Taiwanese Participants With Multiple Myeloma
NCT02286830	PHASE4	COMPLETED	Prolonged Protection From Bone Disease in Multiple Myeloma
NCT02559154	PHASE4	UNKNOWN	Modified Bortezomib-based Combination Therapy for Multiple Myeloma
NCT02577783	PHASE4	UNKNOWN	PDD vs PAD to Treat Initially Diagnosed MM
NCT02773550	PHASE4	TERMINATED	Treatment With a Scheme With Low Doses of Bortezomib / Melphalan / Prednisone (MPV) in Patients With Multiple Myeloma
NCT02958969	PHASE4	COMPLETED	Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
NCT03173092	PHASE4	TERMINATED	A Study of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) for the Treatment of Participants With Multiple Myeloma (MM)
NCT03619252	PHASE4	COMPLETED	Pneumococcal Vaccination of Multiple Myeloma Patients on Novel Agents
NCT03768960	PHASE4	COMPLETED	A Study of DARZALEX (Daratumumab) In Indian Participants With Relapsed and Refractory Multiple Myeloma, Whose Prior Therapy Included a Proteasome Inhibitor and an Immunomodulatory Agent
NCT03829371	PHASE4	ACTIVE_NOT_RECRUITING	STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA
NCT03908138	PHASE4	UNKNOWN	RDD Versus VDD in Newly Diagnosed Patients With Multiple Myeloma
NCT04217967	PHASE4	COMPLETED	Ixazomib, Lenalidomide, and Combination for Maintenance in NDMM Patients
NCT04952766	PHASE4	COMPLETED	Study Evaluating SARS-CoV-2 (COVID-19) Humoral Response After BNT162b2 Vaccine in Immunocompromised Adults Compared to Healthy Adults
NCT04989140	PHASE4	UNKNOWN	Study of Pomalidomide, Oral Dexamethasone and Ixazomib in Patients With Relapsed MM Who Have Received Lenalidomide
NCT05183139	PHASE4	WITHDRAWN	A Multicenter In-class Transition Study of Ixazomib Combined With Pomalidomide and Dexamethasone or With Lenalidomide and Dexamethasone in Adults With Relapsed/Refractory Multiple Myeloma
NCT05201781	PHASE4	RECRUITING	A Long-term Study for Participants Previously Treated With Ciltacabtagene Autoleucel
NCT05429515	PHASE4	NOT_YET_RECRUITING	Effect of HFR-SUPRA in the Treatment of Multiple Myeloma-related Acute Kidney Injury
NCT05511428	PHASE4	COMPLETED	Home Based Daratumumab Administration for Patients With Multiple Myeloma
NCT05545202	PHASE4	UNKNOWN	A Randomized, Comparative, Double-blind Trial of Pentaisomaltose and Dimethyl Sulphoxide for Cryoprotection of Hematopoietic Stem Cells in Subjects With Multiple Myeloma or Malignant Lymphoma With a Need for Autologous Transplantation
NCT05555329	PHASE4	COMPLETED	Alternative Dosing Scheme of Pomalidomide 4 mg Every Other Day Versus Pomalidomide 2 mg and 4 mg Every Day; the POMAlternative Study
NCT05722405	PHASE4	RECRUITING	Ixazomib Plus Low-dose Lenalidomide Versus Ixazomib Alone for Maintenance Treatment of High Risk Multiple Myeloma