AKT2

Summary

AKT2 (AKT serine/threonine kinase 2, HGNC:392) is a protein-coding gene on chromosome 19q13.2, encoding RAC-beta serine/threonine-protein kinase (P31751). Serine/threonine kinase closely related to AKT1 and AKT3. In precision oncology, AKT2 EXPRESSION confers sensitivity to Trastuzumab in Breast Cancer (CIViC Level B); 2 further curated variant–drug associations are listed below.

This gene is a putative oncogene encoding a protein belonging to a subfamily of serine/threonine kinases containing SH2-like (Src homology 2-like) domains, which is involved in signaling pathways. The gene serves as an oncogene in the tumorigenesis of cancer cells For example, its overexpression contributes to the malignant phenotype of a subset of human ductal pancreatic cancers. The encoded protein is a general protein kinase capable of phophorylating several known proteins, and has also been implicated in insulin signaling.

Source: NCBI Gene 208 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypoinsulinemic hypoglycemia and body hemihypertrophy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 255 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 39
• Druggable target: yes — 16 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 3 curated variant–drug associations
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001626

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:392
Approved symbol	AKT2
Name	AKT serine/threonine kinase 2
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	PKBβ
Ensembl gene	ENSG00000105221
Ensembl biotype	protein_coding
OMIM	164731
Entrez	208

Gene structure

Transcript identifiers

Ensembl transcripts: 66 — 45 protein_coding, 9 retained_intron, 6 nonsense_mediated_decay, 6 protein_coding_CDS_not_defined

ENST00000311278, ENST00000358335, ENST00000391844, ENST00000391845, ENST00000392037, ENST00000392038, ENST00000416362, ENST00000416994, ENST00000423127, ENST00000424901, ENST00000427375, ENST00000441941, ENST00000452077, ENST00000456441, ENST00000476247, ENST00000476266, ENST00000480878, ENST00000483166, ENST00000486368, ENST00000486647, ENST00000487537, ENST00000489375, ENST00000491778, ENST00000492463, ENST00000496089, ENST00000497948, ENST00000498350, ENST00000537834, ENST00000578123, ENST00000578282, ENST00000578310, ENST00000578615, ENST00000578975, ENST00000579047, ENST00000579345, ENST00000580747, ENST00000580878, ENST00000581582, ENST00000583859, ENST00000584288, ENST00000596634, ENST00000601166, ENST00000672879, ENST00000672890, ENST00000870029, ENST00000870030, ENST00000870031, ENST00000870032, ENST00000870033, ENST00000870034, ENST00000870035, ENST00000870036, ENST00000870037, ENST00000914212, ENST00000914213, ENST00000948930, ENST00000948931, ENST00000948932, ENST00000948933, ENST00000948934, ENST00000948935, ENST00000948936, ENST00000948937, ENST00000948938, ENST00000948939, ENST00000948940

RefSeq mRNA: 4 — MANE Select: NM_001626 NM_001243027, NM_001243028, NM_001330511, NM_001626

CCDS: CCDS12552, CCDS82350

Canonical transcript exons

ENST00000392038 — 14 exons

Exon	Start	End
ENSE00001510510	40230317	40233951
ENSE00003480378	40237969	40238091
ENSE00003513249	40235045	40235147
ENSE00003514442	40256926	40257054
ENSE00003535774	40238905	40238973
ENSE00003560725	40235890	40236104
ENSE00003566922	40242534	40242687
ENSE00003581266	40235263	40235350
ENSE00003641454	40265222	40265351
ENSE00003653262	40241938	40242069
ENSE00003665305	40236257	40236385
ENSE00003693546	40240045	40240110
ENSE00003786939	40255158	40255269
ENSE00003847892	40285181	40285345

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 98.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.3657 / max 269.4635, expressed in 1821 samples.

FANTOM5 promoters (19 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180972	29.9420	1816
180973	3.0360	1385
180971	1.9545	1268
180970	1.3647	892
180968	0.5786	349
180964	0.5172	242
180967	0.2659	124
180956	0.1925	28
180969	0.1619	57
180963	0.1248	47

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.86	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.71	gold quality
right lobe of thyroid gland	UBERON:0001119	98.69	gold quality
left lobe of thyroid gland	UBERON:0001120	98.58	gold quality
metanephros cortex	UBERON:0010533	98.46	gold quality
cerebellar hemisphere	UBERON:0002245	98.45	gold quality
left ovary	UBERON:0002119	98.26	gold quality
cerebellar cortex	UBERON:0002129	98.25	gold quality
thyroid gland	UBERON:0002046	98.14	gold quality
right ovary	UBERON:0002118	98.07	gold quality
body of uterus	UBERON:0009853	97.99	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.97	gold quality
endocervix	UBERON:0000458	97.92	gold quality
gastrocnemius	UBERON:0001388	97.64	gold quality
adenohypophysis	UBERON:0002196	97.55	gold quality
left uterine tube	UBERON:0001303	97.47	gold quality
ectocervix	UBERON:0012249	97.39	gold quality
right adrenal gland cortex	UBERON:0035827	97.31	gold quality
adrenal tissue	UBERON:0018303	97.26	gold quality
right adrenal gland	UBERON:0001233	97.24	gold quality
sural nerve	UBERON:0015488	97.19	gold quality
stromal cell of endometrium	CL:0002255	97.17	gold quality
body of pancreas	UBERON:0001150	97.05	gold quality
left adrenal gland cortex	UBERON:0035825	97.05	gold quality
left adrenal gland	UBERON:0001234	97.04	gold quality
muscle of leg	UBERON:0001383	97.04	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.03	gold quality
right lobe of liver	UBERON:0001114	97.01	gold quality
gall bladder	UBERON:0002110	96.97	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.21

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, ESR1, FOXO3, MEF2A, MYOD1, MYOG, NFKB1, PROX1, RELA, SMAD5, SNAI1, TCF7L2, TP53, TWIST1, YBX1

miRNA regulators (miRDB)

116 targeting AKT2, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• In renal tubular epithelial cell, Akt phosphorylation is up-regulated in an effort to minimize cell death. (PMID:12114503)
• Activation of AKT consequent to binding of albumin by CLL cells blocks chlorambucil- and radiation-induced apoptosis. (PMID:12480711)
• a new mechanism for androgen-mediated prostate cancer cell survival and establish FKHR as nuclear target for both AKT-dependent and -independent survival signals in prostate cancer cells. (PMID:12482965)
• Results describe the structure of an inactive and unliganded Akt2 kinase domain, and several features that distinguish it from other kinases. (PMID:12517337)
• data indicate that AKT2 mediates PI3-K-dependent effects on adhesion, motility, invasion, and metastasis in vivo (PMID:12517798)
• results show that a defect in the ability of insulin to activate Akt-2 and -3 may explain the impaired insulin-stimulated glucose transport in insulin resistance (PMID:12663464)
• both p70S6K and Akt are activated in the majority of human papillary cancer cells. (PMID:12733712)
• Akt regulates basic helix-loop-helix transcription factor-coactivator complex formation and activity during neuronal differentiation (PMID:12808085)
• Akt2 phosphorylates MLK3, which results in the disassembly of the JNK complex bound to POSH and down-regulation of the JNK signaling pathway (PMID:14504284)
• Akt2 may be an important regulator of both Xiap and p53 contents in ovarian cancer after CDDP challenge. (PMID:14612499)
• Our data suggest that Akt is an endogenous inhibitor during TRAIL-mediated synovial cell apoptotic pathway. (PMID:14637151)
• Findings suggest that Akt2 is a novel independent predictor for the development and progression of hepatocellular carcinoma . (PMID:14654898)
• Lipid rafts(LR) may play important role in determining function of PI 3-K/Akt2 signaling, including stimulation of intestinal Na absorption. LR-associated Akt2 may be involved in enterocyte differentiation. (PMID:14699494)
• data suggest that upstream perturbations of the PI3K/AKT pathway contribute to frequent activation of AKT2 in pancreatic cancer, which may contribute to the pathogenesis of this highly aggressive form of human malignancy (PMID:14735903)
• Thus a physiological concentration of insulin stimulated Akt-1 & Akt-2 phosphorylation in human skeletal muscle in the absence of hyperglycemia, but Akt-2 expression is impaired in muscle of obese patients with atypical diabetes with severe hyperglycemia. (PMID:15010337)
• activated Akt and Akt2 have roles in progression of pancreatic ductal adenocarcinoma (PMID:15102693)
• These results suggest that cross-talk between the PKB and caspase-8 pathways may regulate the balance between cell survival and cell death in ECV304. (PMID:15111130)
• a mutation in AKT2 in a family showing autosomal dominant inheritance of severe insulin resistance and diabetes mellitus is described; the mutant kinase in cultured cells disrupted insulin signaling and inhibited the function of coexpressed, wild-type AKT (PMID:15166380)
• Akt2 is a critical kinase that regulates ezrin phosphorylation and activation (PMID:15531580)
• AKT2 plays an important role in glioma cell motility and invasion (PMID:15557754)
• Kinetic analysis of GST-AKT2 demonstrates that phosphorylation of Thr309 in the activation loop of the kinase is largely responsible for observed reduction in Km & for a subsequent 150-fold increase in the catalytic efficiency (k(cat)/Km) of the enzyme. (PMID:15890450)
• in breast cancer patients, Akt activation is associated with tumour proliferation and poor prognosis, particularly in the subset of patients with ErbB2-overexpressing tumours (PMID:15987444)
• In this study, we provide evidence for isoform-specific positive and negative roles for Akt1 and -2 in regulating growth factor-stimulated phenotypes in breast epithelial cells (PMID:16365168)
• results suggest that AKT pathway may play an important role in the development and progression of gliomas (PMID:16402276)
• These data show that specific interaction of the Akt2 isoform with p21 is key to its negative effect on normal cell cycle progression. (PMID:16982699)
• Akt1 and Akt2 have opposing roles in Rac/Pak signaling and cell migration (PMID:17012749)
• Akt1 induces CREB phosphorylation at Ser-133 and CREB target gene expression. (PMID:17276404)
• Sequencing of the entire coding region and splice junctions of AKT2 and the relationship of genetic variations in the gene with multiple metabolic diseases is reported. (PMID:17327441)
• Twist as a positive transcriptional regulator of AKT2 expression; Twist-AKT2 signaling is involved in promoting invasive ability and survival of breast cancer cells. (PMID:17332325)
• Changes in tissue pressure during inflammation may regulate macrophage phagocytosis by activation of PI-3K, which activates Akt2, mTOR, and p70S6K. (PMID:17372934)
• the PI3K/AKT/mTOR signaling pathway is involved in regulation of SphK1, with AKT2 playing a key role in PDGF-induced SphK1 expression (PMID:17482291)
• Two variants in 5’ regulatory region of Akt2 gene are associated and may modulate susceptibility to insulin resistance and related metabolic abnormalities. (PMID:17576055)
• AKT2 up-regulation is characteristic of skin squamous cell carcinoma and coincident AKT2 activation through serine phosphorylation correlates with malignancy. (PMID:17804734)
• Pressure did not stimulate translocation of AKT2 to the plasma membrane. (PMID:17825284)
• PKB[alpha] and/or PKB[gamma] and not PKB[beta] alone are involved in gemcitabine resistance mechanisms. (PMID:17895832)
• Akt2 is required for rapamycin-induced vascular smooth muscle cell differentiation, whereas Akt1 appears to oppose contractile protein expression. (PMID:17908691)
• Akt1 and Akt2 mediate GPIb-IX signaling via the cGMP-dependent signaling pathway. (PMID:17914025)
• a key regulatory role of the Akt/mTOR pathway in the generation of the effects of As(2)O(3) (PMID:18048359)
• Functional convergence of Twist and AKT2 underscores the importance of this signaling pathway in tumor development and progression. (PMID:18281467)
• Dlx5 can act as an oncogene by cooperating with Akt2 to promote lymphomagenesis (PMID:18316591)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	akt2	ENSDARG00000011219
danio_rerio	akt2l	ENSDARG00000103612
mus_musculus	Akt2	ENSMUSG00000004056
rattus_norvegicus	Akt2	ENSRNOG00000018677

Paralogs (5): PRKCQ (ENSG00000065675), AKT3 (ENSG00000117020), PDPK1 (ENSG00000140992), AKT1 (ENSG00000142208), PRKCD (ENSG00000163932)

Protein

Protein identifiers

RAC-beta serine/threonine-protein kinase — P31751 (reviewed: P31751)

Alternative names: Protein kinase Akt-2, Protein kinase B beta, RAC protein kinase beta

All UniProt accessions (24): A0A0A0MRF1, A0A1B0GXA2, A0A5F9ZHJ8, A8MX96, C9J258, C9JC83, C9JHS6, C9JIF6, C9JIJ1, E7EVP8, P31751, J3KRI8, J3KSY8, J3KT31, J3KTC6, J3KTP4, J3QKW1, J3QL45, J3QLS6, M0QZK3, M0QZW8, M0R0P9, M0R275, M0R283

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine kinase closely related to AKT1 and AKT3. All 3 enzymes, AKT1, AKT2 and AKT3, are collectively known as AKT kinase. AKT regulates many processes including metabolism, proliferation, cell survival, growth and angiogenesis, through the phosphorylation of a range of downstream substrates. Over 100 substrates have been reported so far, although for most of them, the precise AKT kinase catalyzing the reaction was not specified. AKT regulates glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at ‘Ser-50’ negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT also regulates the storage of glucose in the form of glycogen by phosphorylating GSK3A at ‘Ser-21’ and GSK3B at ‘Ser-9’, resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT also regulates cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of ‘Ser-83’ decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at ‘Ser-939’ and ‘Thr-1462’, thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at ‘Thr-24’, ‘Ser-256’ and ‘Ser-319’. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates ‘Ser-454’ on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of ‘Ser-273’, resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on ‘Ser-318’, which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1). AKT mediates the antiapoptotic effects of IGF1. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development. In response to lysophosphatidic acid stimulation, inhibits the ciliogenesis cascade. In this context, phosphorylates WDR44, hence stabilizing its interaction with Rab11 and preventing the formation of the ciliogenic Rab11-FIP3-RAB3IP complex. Also phosphorylates RAB3IP/Rabin8, thus may affect RAB3IP guanine nucleotide exchange factor (GEF) activity toward Rab8, which is important for cilia growth. Phosphorylates PKP1, facilitating its interaction with YWHAG and translocation to the nucleus, ultimately resulting in a reduction in keratinocyte intercellular adhesion. Phosphorylation of PKP1 increases PKP1 protein stability, translocation to the cytoplasm away from desmosome plaques and PKP1-driven cap-dependent translation. Several AKT2-specific substrates have been identified, including ANKRD2, C2CD5, CLK2 and PITX2. May play a role in myoblast differentiation. In this context, may act through PITX2 phosphorylation. Unphosphorylated PITX2 associates with an ELAVL1/HuR-containing complex, which stabilizes CCND1 cyclin mRNA, ensuring cell proliferation. Phosphorylation by AKT2 impairs this association, leading to CCND1 mRNA destabilization and progression towards differentiation. Also involved in the negative regulation of myogenesis in response to stress conditions. In this context, acts by phosphorylating ANKRD2. May also be a key regulator of glucose uptake. Regulates insulin-stimulated glucose transport by the increase of glucose transporter GLUT4 translocation from intracellular stores to the plasma membrane. In this context, acts by phosphorylating C2CD5/CDP138 on ‘Ser-197’ in insulin-stimulated adipocytes. Through the phosphorylation of CLK2 on ‘Thr-343’, involved in insulin-regulated suppression of hepatic gluconeogenesis.

Subunit / interactions. Interacts with BTBD10. Interacts with KCTD20. Interacts (via PH domain) with MTCP1, TCL1A and TCL1B; this interaction may facilitate AKT2 oligomerization and phosphorylation, hence increasing kinase activity. Interacts with PHB2; this interaction may be important for myogenic differentiation. Interacts (when phosphorylated) with CLIP3/ClipR-59; this interaction promotes AKT2 recruitment to the plasma membrane. Interacts with WDFY2/ProF (via WD repeats 1-3).

Subcellular location. Cytoplasm. Nucleus. Cell membrane. Early endosome.

Tissue specificity. Widely expressed. Expressed in myoblasts.

Post-translational modifications. Phosphorylation on Thr-309 and Ser-474 is required for full activity. Phosphorylation of the activation loop at Thr-309 by PDPK1/PDK1 is a prerequisite for full activation. Phosphorylated and activated by PDPK1/PDK1 in the presence of phosphatidylinositol 3,4,5-trisphosphate. Phosphorylation by mTORC2 in response to growth factors plays a key role in AKT1 activation: mTORC2 phosphorylates different sites depending on the context, such as Ser-474 or Ser-478, thereby facilitating subsequent phosphorylation of the activation loop by PDPK1/PDK1. Ubiquitinated; undergoes both ‘Lys-48’- and ‘Lys-63’-linked polyubiquitination. TRAF6 catalyzes ‘Lys-63’-linked AKT2 ubiquitination; this modification may be important for AKT2 recruitment to the plasma membrane and for AKT2 activating phosphorylation. When phosphorylated, undergoes ‘Lys-48’-polyubiquitination catalyzed by TTC3 in the nucleus, leading to its degradation by the proteasome. O-GlcNAcylation at Thr-306 and Thr-313 inhibits activating phosphorylation at Thr-309 via the disruption of the interaction between AKT and PDPK1/PDK1.

Disease relevance. Defects in AKT2 are a cause of susceptibility to breast cancer (BC). AKT2 promotes metastasis of tumor cells without affecting the latency of tumor development. May play a role in glioblastoma cell survival. Type 2 diabetes mellitus (T2D) [MIM:125853] A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Disease susceptibility is associated with variants affecting the gene represented in this entry. Hypoinsulinemic hypoglycemia with hemihypertrophy (HIHGHH) [MIM:240900] A disorder characterized by hypoglycemia, low insulin levels, low serum levels of ketone bodies and branched-chain amino acids, left-sided hemihypertrophy, neonatal macrosomia, reduced consciousness and hypoglycemic seizures. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Phosphorylation at Thr-309 (in the kinase domain) and Ser-474 (in the C-terminal regulatory region) is required for full activation. In adipocytes and hepatocytes, the activation is induced by insulin. Aminofurazans, such as 4-[2-(4-amino-2,5-dihydro-1,2,5-oxadiazol-3-yl)-6-{[(1S)-3-amino-1-phenylpropyl]oxy}-1-ethyl-1H-imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol (compound 32), are potent AKT2 inhibitors. AKT2 phosphorylation of PKP1 is induced by insulin.

Domain organisation. Binding of the PH domain to phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) following phosphatidylinositol 3-kinase alpha (PIK3CA) activation results in AKT2 recruitment to the plasma membrane, exposition of a pair of serine and threonine residues for phosphorylation by membrane-associated PDPK1/PDK1 and activation.

Similarity. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P31751-1	1	yes
P31751-2	2

RefSeq proteins (4): NP_001229956, NP_001229957, NP_001317440, NP_001617* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR001849	PH_domain	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR017892	Pkinase_C	Domain
IPR034677	Akt2	Domain
IPR039026	PH_PKB	Domain

Pfam: PF00069, PF00169, PF00433

Enzyme classification (BRENDA):

• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
KKRAARATSNVFA	0.013–0.045	3
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (81 total): strand 23, helix 17, modified residue 8, turn 6, glycosylation site 5, mutagenesis site 5, sequence variant 4, binding site 4, domain 3, disulfide bond 2, chain 1, splice variant 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

19 structures.

PDB	Method	Resolution (Å)
1O6L	X-RAY DIFFRACTION	1.6
1O6K	X-RAY DIFFRACTION	1.7
2JDO	X-RAY DIFFRACTION	1.8
2X39	X-RAY DIFFRACTION	1.93
3D0E	X-RAY DIFFRACTION	2
9C1W	X-RAY DIFFRACTION	2
2UW9	X-RAY DIFFRACTION	2.1
1GZK	X-RAY DIFFRACTION	2.3
2JDR	X-RAY DIFFRACTION	2.3
3E87	X-RAY DIFFRACTION	2.3
8Q61	X-RAY DIFFRACTION	2.32
1GZN	X-RAY DIFFRACTION	2.5
3E88	X-RAY DIFFRACTION	2.5
3E8D	X-RAY DIFFRACTION	2.7
2XH5	X-RAY DIFFRACTION	2.72
1GZO	X-RAY DIFFRACTION	2.75
1MRV	X-RAY DIFFRACTION	2.8
1MRY	X-RAY DIFFRACTION	2.8
1P6S	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31751-F1	82.79	0.51

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): 275 (proton acceptor)

Ligand- & substrate-binding residues (4): 158–166; 181; 280; 293

Post-translational modifications (8): 34, 126, 309, 447, 451, 474, 478, 1

Disulfide bonds (2): 60–77, 297–311

Glycosylation sites (5): 128, 131, 306, 313, 474

Mutagenesis-validated functional residues (5):

Position	Phenotype
181	loss of kinase activity.
309	impairs interaction with ttc3; when associated with a-474.
309	constitutively active; when associated with d-474.
474	impairs interaction with ttc3; when associated with a-309.
474	constitutively active; when associated with e-309.

Function

Pathways and Gene Ontology

Reactome pathways

98 pathways

ID	Pathway
R-HSA-111447	Activation of BAD and translocation to mitochondria
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1358803	Downregulation of ERBB2:ERBB3 signaling
R-HSA-1445148	Translocation of SLC2A4 (GLUT4) to the plasma membrane
R-HSA-165158	Activation of AKT2
R-HSA-165159	MTOR signalling
R-HSA-165160	PDE3B signalling
R-HSA-165181	Inhibition of TSC complex formation by AKT (PKB)
R-HSA-198323	AKT phosphorylates targets in the cytosol
R-HSA-198693	AKT phosphorylates targets in the nucleus
R-HSA-199418	Negative regulation of the PI3K/AKT network
R-HSA-211163	AKT-mediated inactivation of FOXO1A
R-HSA-3769402	Deactivation of the beta-catenin transactivating complex
R-HSA-389357	CD28 dependent PI3K/Akt signaling
R-HSA-389513	Co-inhibition by CTLA4
R-HSA-392451	G beta:gamma signalling through PI3Kgamma
R-HSA-5218920	VEGFR2 mediated vascular permeability
R-HSA-5628897	TP53 Regulates Metabolic Genes
R-HSA-5674400	Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-6804757	Regulation of TP53 Degradation
R-HSA-6804758	Regulation of TP53 Activity through Acetylation
R-HSA-6804759	Regulation of TP53 Activity through Association with Co-factors
R-HSA-69202	Cyclin E associated events during G1/S transition
R-HSA-69656	Cyclin A:Cdk2-associated events at S phase entry
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs
R-HSA-8941332	RUNX2 regulates genes involved in cell migration
R-HSA-8948751	Regulation of PTEN stability and activity
R-HSA-9607240	FLT3 Signaling
R-HSA-9614399	Regulation of localization of FOXO transcription factors
R-HSA-9634638	Estrogen-dependent nuclear events downstream of ESR-membrane signaling

MSigDB gene sets: 714 (showing top): GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_CYTOPLASMIC_TRANSLATION, GOBP_LIPID_MODIFICATION, CREL_01, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_EPITHELIUM_DEVELOPMENT, FREAC2_01, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, REACTOME_ADAPTIVE_IMMUNE_SYSTEM

GO Biological Process (32): glycogen biosynthetic process (GO:0005978), glucose metabolic process (GO:0006006), signal transduction (GO:0007165), insulin receptor signaling pathway (GO:0008286), negative regulation of long-chain fatty acid import across plasma membrane (GO:0010748), positive regulation of glucose metabolic process (GO:0010907), regulation of cell migration (GO:0030334), positive regulation of cell migration (GO:0030335), positive regulation of fatty acid beta-oxidation (GO:0032000), peripheral nervous system myelin maintenance (GO:0032287), cellular response to insulin stimulus (GO:0032869), intracellular signal transduction (GO:0035556), protein modification process (GO:0036211), negative regulation of apoptotic process (GO:0043066), positive regulation of blood vessel endothelial cell migration (GO:0043536), fat cell differentiation (GO:0045444), positive regulation of glycogen biosynthetic process (GO:0045725), positive regulation of D-glucose import across plasma membrane (GO:0046326), protein stabilization (GO:0050821), regulation of cell cycle (GO:0051726), mammary gland epithelial cell differentiation (GO:0060644), cellular response to high light intensity (GO:0071486), protein localization to plasma membrane (GO:0072659), positive regulation of protein targeting to membrane (GO:0090314), retinal rod cell apoptotic process (GO:0097473), positive regulation of cap-dependent translational initiation (GO:1903676), negative regulation of PERK-mediated unfolded protein response (GO:1903898), positive regulation of cell motility (GO:2000147), glycogen metabolic process (GO:0005977), regulation of translation (GO:0006417), protein phosphorylation (GO:0006468), apoptotic process (GO:0006915)

GO Molecular Function (10): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), metal ion binding (GO:0046872), protein serine kinase activity (GO:0106310), molecular function activator activity (GO:0140677), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), early endosome (GO:0005769), cytosol (GO:0005829), plasma membrane (GO:0005886), cell cortex (GO:0005938), ruffle membrane (GO:0032587), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-18 pathways:

Category	Pathways
PIP3 activates AKT signaling	3
Activation of BH3-only proteins	1
Intracellular signaling by second messengers	1
Downregulation of ERBB2 signaling	1
Membrane Trafficking	1
PI3K Cascade	1
Signal Transduction	1
PKB-mediated events	1
MTOR signalling	1
Regulation of gene expression in beta cells	1
TCF dependent signaling in response to WNT	1
Co-stimulation by CD28	1
Regulation of T cell activation by CD28 family	1
G-protein beta:gamma signalling	1
VEGFA-VEGFR2 Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
regulation of cellular process	2
cell migration	2
intracellular anatomical structure	2
protein kinase activity	2
cytoplasm	2
cell periphery	2
glycogen metabolic process	1
glucan biosynthetic process	1
hexose metabolic process	1
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
regulation of long-chain fatty acid import across plasma membrane	1
long-chain fatty acid import across plasma membrane	1
negative regulation of transmembrane transport	1
negative regulation of long-chain fatty acid import into cell	1
glucose metabolic process	1
regulation of glucose metabolic process	1
positive regulation of carbohydrate metabolic process	1
positive regulation of small molecule metabolic process	1
regulation of cell motility	1
regulation of cell migration	1
positive regulation of cell motility	1
fatty acid beta-oxidation	1
regulation of fatty acid beta-oxidation	1
positive regulation of fatty acid oxidation	1
positive regulation of lipid catabolic process	1
myelination in peripheral nervous system	1
myelin maintenance	1
response to insulin	1
cellular response to peptide hormone stimulus	1
signal transduction	1
protein metabolic process	1
macromolecule modification	1
apoptotic process	1
regulation of apoptotic process	1

Protein interactions and networks

STRING

3858 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AKT2	PHLPP1	O60346	949
AKT2	TBC1D4	O60343	946
AKT2	APPL1	Q9UKG1	900
AKT2	PHLPP2	Q6ZVD8	870
AKT2	PIK3CA	P42336	841
AKT2	INS	P01308	841
AKT2	FOXO1	Q12778	817
AKT2	IRS1	P35568	815
AKT2	SLC2A4	P14672	797
AKT2	RICTOR	Q6R327	792
AKT2	PIK3R1	P27986	790
AKT2	PIK3CB	P42338	783
AKT2	RPTOR	Q8N122	769
AKT2	PTEN	P60484	767
AKT2	PLEK2	Q9NYT0	766

IntAct

85 interactions, top by confidence:

A	B	Type	Score
PSMD9	PSMC3	psi-mi:“MI:0914”(association)	0.940
XAF1	AKT1	psi-mi:“MI:0914”(association)	0.670
AKT1	AKT2	psi-mi:“MI:0915”(physical association)	0.640
AKT1	AKT2	psi-mi:“MI:0914”(association)	0.640
AKT2	UBE2O	psi-mi:“MI:0915”(physical association)	0.620
TTC3	AKT2	psi-mi:“MI:0915”(physical association)	0.580
AKT2	TTC3	psi-mi:“MI:0915”(physical association)	0.580
AKT2	REL	psi-mi:“MI:0915”(physical association)	0.560
AKT2	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
SORBS3	AKT2	psi-mi:“MI:0915”(physical association)	0.560
	AKT2	psi-mi:“MI:0915”(physical association)	0.560
AKT2	PICK1	psi-mi:“MI:0915”(physical association)	0.560
NR2F2	GC	psi-mi:“MI:0914”(association)	0.530
CDK3	GMNN	psi-mi:“MI:0914”(association)	0.530
AKT2	UBB	psi-mi:“MI:0914”(association)	0.530
AKT2	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.520
HSP90AB1	AKT2	psi-mi:“MI:0915”(physical association)	0.520
GSK3B	AKT2	psi-mi:“MI:0407”(direct interaction)	0.440
AKT2	SH3RF1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
AKT2		psi-mi:“MI:0217”(phosphorylation reaction)	0.440
AKT2	MYH13	psi-mi:“MI:0407”(direct interaction)	0.440
AKT2	CASP3	psi-mi:“MI:0194”(cleavage reaction)	0.440

BioGRID (179): AKT2 (Affinity Capture-Western), PRKCZ (Affinity Capture-Western), AKT2 (Affinity Capture-Western), CLIP3 (Affinity Capture-Western), AKT2 (Reconstituted Complex), AKT2 (Reconstituted Complex), PLEKHO1 (Affinity Capture-Western), SNAI1 (Affinity Capture-Western), AKT2 (Reconstituted Complex), HIST1H3A (Biochemical Activity), AKT2 (Affinity Capture-Western), AKT2 (Co-localization), APPL1 (Two-hybrid), AKT2 (Affinity Capture-Western), AKT2 (Reconstituted Complex)

ESM2 similar proteins: A2YNT8, A2ZAB5, A9TF79, B6F107, O64812, P0C5D6, P19784, P21869, P31748, P31749, P31750, P31751, P43291, P43292, P47196, P47197, P49137, P49138, P49139, Q01314, Q02066, Q0D4J7, Q16644, Q2QY53, Q39192, Q39193, Q3SYZ2, Q3UMW7, Q5N942, Q60823, Q63484, Q66H84, Q6X4A2, Q6ZI44, Q6ZLP5, Q75H77, Q75LR7, Q75V57, Q7XKA8, Q7XQP4

Diamond homologs: A1A4I4, A1Z7T0, A1Z9X0, A7MBL8, A8KBH6, A8WUG4, F1M7Y5, O08874, O19111, O42632, P04409, P05126, P05128, P05129, P05130, P05696, P05771, P05772, P09215, P09216, P09217, P10102, P10829, P10830, P13677, P13678, P16054, P17252, P20444, P23298, P24583, P24723, P28867, P31748, P31749, P31750, P31751, P34722, P34885, P36582

SIGNOR signaling

151 interactions.

A	Effect	B	Mechanism
AKT2	“down-regulates activity”	MAP3K5	phosphorylation
AKT2	“down-regulates activity”	MAPK14
AKT2	up-regulates	MTOR
TNF	up-regulates	AKT2
AKT2	“up-regulates quantity by stabilization”	MDM2	phosphorylation
AKT2	“up-regulates activity”	MDM2	phosphorylation
AKT2	up-regulates	XIAP	phosphorylation
AKT2	down-regulates	CASP9	phosphorylation
AKT2	up-regulates	EZR	phosphorylation
PDPK1	“up-regulates activity”	AKT2	phosphorylation
PHLPP1	unknown	AKT2	dephosphorylation
AKT2	down-regulates	GSK3A	phosphorylation
AKT2	“up-regulates activity”	CTNNB1
GNG12	up-regulates	AKT2	binding
PIK3CA	up-regulates	AKT2
FHIT	down-regulates	AKT2
AKT2	up-regulates	EP300	phosphorylation
AKT2	“down-regulates activity”	CDKN1A	binding
AKT2	down-regulates	AKT1S1	phosphorylation
AKT2	up-regulates	CTNNB1	phosphorylation
AKT2	down-regulates	HTRA2	phosphorylation
PHLPP1	down-regulates	AKT2	dephosphorylation
AKT2	down-regulates	SH3RF1	phosphorylation
AKT2	down-regulates	PPARGC1A	phosphorylation
AKT2	up-regulates	NFKB1
AKT2	up-regulates	GLI1
AKT2	down-regulates	STK3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 60 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
Programmed Cell Death	5	15.6×	3e-03
Diseases of signal transduction by growth factor receptors and second messengers	6	7.2×	7e-03
Vesicle-mediated transport	8	5.9×	4e-03
Membrane Trafficking	7	5.5×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	5	18.2×	2e-03
positive regulation of gene expression	9	6.0×	3e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	75
Likely benign	105
Benign	33

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
29804	NM_001626.6(AKT2):c.49G>A (p.Glu17Lys)	Pathogenic
13982	NM_001626.6(AKT2):c.821G>A (p.Arg274His)	Likely pathogenic

SpliceAI

3435 predictions. Top by Δscore:

Variant	Effect	Δscore
19:40235043:A:AC	donor_gain	1.0000
19:40235044:C:CC	donor_gain	1.0000
19:40235044:CAG:C	donor_gain	1.0000
19:40235148:C:CC	acceptor_gain	1.0000
19:40235884:CCTCA:C	donor_loss	1.0000
19:40235885:CTCA:C	donor_loss	1.0000
19:40235886:TCACC:T	donor_loss	1.0000
19:40235887:CA:C	donor_loss	1.0000
19:40235888:A:AC	donor_gain	1.0000
19:40235888:ACCTC:A	donor_loss	1.0000
19:40235889:C:A	donor_loss	1.0000
19:40235889:C:CC	donor_gain	1.0000
19:40235889:CCT:C	donor_gain	1.0000
19:40236104:CCTGA:C	acceptor_loss	1.0000
19:40236105:C:CC	acceptor_gain	1.0000
19:40236105:CTGA:C	acceptor_loss	1.0000
19:40236111:A:C	acceptor_gain	1.0000
19:40236258:T:TA	donor_gain	1.0000
19:40236260:AGGCG:A	donor_gain	1.0000
19:40236271:A:AC	donor_gain	1.0000
19:40236272:C:CC	donor_gain	1.0000
19:40236274:C:CA	donor_gain	1.0000
19:40236315:ATGC:A	donor_gain	1.0000
19:40236381:TCCAG:T	acceptor_gain	1.0000
19:40236382:CCAG:C	acceptor_gain	1.0000
19:40236382:CCAGC:C	acceptor_gain	1.0000
19:40236383:CAG:C	acceptor_gain	1.0000
19:40236383:CAGC:C	acceptor_gain	1.0000
19:40236384:AG:A	acceptor_gain	1.0000
19:40236385:GC:G	acceptor_loss	1.0000

AlphaMissense

3194 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:40233899:G:C	F473L	1.000
19:40233899:G:T	F473L	1.000
19:40233901:A:G	F473L	1.000
19:40235082:A:C	F443L	1.000
19:40235082:A:T	F443L	1.000
19:40235084:A:G	F443L	1.000
19:40235350:C:A	R392S	1.000
19:40235350:C:G	R392S	1.000
19:40235890:C:A	R392M	1.000
19:40235890:C:G	R392T	1.000
19:40235911:A:G	L385P	1.000
19:40235980:A:T	I362N	1.000
19:40235983:A:G	L361P	1.000
19:40235988:G:C	F359L	1.000
19:40235988:G:T	F359L	1.000
19:40235990:A:G	F359L	1.000
19:40235990:A:T	F359I	1.000
19:40235992:A:G	L358P	1.000
19:40236015:G:C	F350L	1.000
19:40236015:G:T	F350L	1.000
19:40236017:A:G	F350L	1.000
19:40236017:A:T	F350I	1.000
19:40236019:G:C	P349R	1.000
19:40236019:G:T	P349H	1.000
19:40236055:C:T	G337D	1.000
19:40236056:C:G	G337R	1.000
19:40236062:C:A	G335W	1.000
19:40236062:C:G	G335R	1.000
19:40236062:C:T	G335R	1.000
19:40236063:C:A	W334C	1.000

dbSNP variants (sampled 300 via entrez): RS1000006757 (19:40273899 A>G), RS1000110581 (19:40274601 G>A), RS1000158024 (19:40261611 C>A), RS1000165422 (19:40268483 C>A,T), RS1000238272 (19:40239159 GC>G), RS1000286260 (19:40245140 A>G,T), RS1000292443 (19:40239165 C>A,G,T), RS1000296868 (19:40283429 G>A), RS1000327146 (19:40233845 C>T), RS1000405755 (19:40278200 GC>G), RS1000464413 (19:40269469 C>T), RS1000506397 (19:40230209 A>G), RS1000516491 (19:40269690 G>C,T), RS1000599817 (19:40256700 G>A), RS1000720819 (19:40262445 G>A)

Disease associations

OMIM: gene MIM:164731 | disease phenotypes: MIM:125853, MIM:240900

GenCC curated gene-disease

Disease	Classification	Inheritance
hypoinsulinemic hypoglycemia and body hemihypertrophy	Definitive	Autosomal dominant
diabetes mellitus, noninsulin-dependent	Strong	Autosomal dominant
AKT2-related familial partial lipodystrophy	Strong	Autosomal dominant
type 2 diabetes mellitus	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
AKT2-related familial partial lipodystrophy	Limited	AD
hypoinsulinemic hypoglycemia and body hemihypertrophy	Definitive	AD

Mondo (4): type 2 diabetes mellitus (MONDO:0005148), hypoinsulinemic hypoglycemia and body hemihypertrophy (MONDO:0009416), (MONDO:0007455), AKT2-related familial partial lipodystrophy (MONDO:0019192)

Orphanet (1): Hypoinsulinemic hypoglycemia and body hemihypertrophy (Orphanet:293964)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000147	Polycystic ovaries
HP:0000324	Facial asymmetry
HP:0000771	Gynecomastia
HP:0000831	Insulin-resistant diabetes mellitus
HP:0000855	Insulin resistance
HP:0000876	Oligomenorrhea
HP:0000956	Acanthosis nigricans
HP:0001325	Hypoglycemic coma
HP:0001397	Hepatic steatosis
HP:0001513	Obesity
HP:0001520	Large for gestational age
HP:0001528	Hemihypertrophy
HP:0001561	Polyhydramnios
HP:0001943	Hypoglycemia
HP:0001956	Truncal obesity
HP:0001958	Nonketotic hypoglycemia
HP:0001985	Hypoketotic hypoglycemia
HP:0001998	Neonatal hypoglycemia
HP:0002069	Bilateral tonic-clonic seizure
HP:0002155	Hypertriglyceridemia
HP:0002173	Hypoglycemic seizures
HP:0002240	Hepatomegaly
HP:0002960	Autoimmunity
HP:0003162	Fasting hypoglycemia
HP:0003292	Decreased serum leptin
HP:0003577	Congenital onset
HP:0003584	Late onset
HP:0003593	Infantile onset
HP:0005978	Type II diabetes mellitus

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003070_1	Cerebrospinal T-tau levels	2.000000e-07
GCST003079_3	Cerebrospinal fluid t-tau:AB1-42 ratio	2.000000e-06
GCST004777_43	Diastolic blood pressure	8.000000e-07
GCST004777_71	Diastolic blood pressure	2.000000e-09
GCST008153_41	Lean body mass	8.000000e-06
GCST008362_31	Birth weight	3.000000e-09
GCST90002388_368	Lymphocyte count	8.000000e-12

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004760	t-tau measurement
EFO:0007708	t-tau:beta-amyloid 1-42 ratio measurement
EFO:0006336	diastolic blood pressure
EFO:0004995	lean body mass
EFO:0004344	birth weight
EFO:0004587	lymphocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003924	Diabetes Mellitus, Type 2	C18.452.394.750.149; C19.246.300

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL2111353 (PROTEIN FAMILY), CHEMBL2431 (SINGLE PROTEIN), CHEMBL4106175 (PROTEIN FAMILY), CHEMBL5169082 (PROTEIN-PROTEIN INTERACTION), CHEMBL6177912 (PROTEIN-PROTEIN INTERACTION), CHEMBL6177913 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

16 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 102,260 (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
CHEMBL2325741	CAPIVASERTIB	4	2,157
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL2177390	IPATASERTIB	3	2,231
CHEMBL2219422	AFURESERTIB	3	1,467
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL4297188	MIRANSERTIB	2	769
CHEMBL1079175	MK-2206	2	3,008
CHEMBL1980715	LAUROGUADINE	2	294
CHEMBL3137336	UPROSERTIB	2	1,624
CHEMBL565612	SOTRASTAURIN	2	1,355
CHEMBL3544960	AT-13148	1	779
CHEMBL494089	GSK-690693	1	2,061
CHEMBL4751394	BAY-1125976	1	89
CHEMBL4802156	VEVORISERTIB	1	70

Clinical evidence (CIViC)

Drug × variant × indication: 3 predictive associations from 3 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
AKT2 EXPRESSION	Trastuzumab	Breast Cancer	Sensitivity/Response	CIViC B	EID706
MTOR Mutation OR PIK3CA Mutation OR PTEN Mutation OR AKT1 Mutation OR AKT2 Mutation	Sapanisertib	Solid Tumor	Sensitivity/Response	CIViC B	EID12075
AKT2 Amplification	Vandetanib + Everolimus	Lung Adenocarcinoma	Sensitivity/Response	CIViC C	EID1621

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs34716810	AKT2		0.00	0
rs62107593	AKT2		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Akt (Protein kinase B, PKB) family

Most potent curated ligand interactions (19 total), top 19:

Ligand	Action	Affinity	Parameter
rizavasertib	Inhibition	9.8	pKi
compound E22 [PMID: 31298542]	Inhibition	8.92	pIC50
uprosertib	Inhibition	8.85	pKi
pifusertib	Inhibition	8.8	pIC50
afuresertib	Inhibition	8.7	pKi
miransertib	Inhibition	8.35	pIC50
NTQ1062	Inhibition	8.2	pIC50
capivasertib	Inhibition	8.1	pIC50
MK-2206	Negative	7.92	pIC50
compound 1 [PMID: 20005102]	Inhibition	7.92	pIC50
GSK690693	Inhibition	7.89	pIC50
BAY1125976	Negative	7.74	pIC50
ipatasertib	Inhibition	7.74	pIC50
MS15	Inhibition	7.05	pIC50
engasertib	Inhibition	7.05	pIC50
Hu7691	Inhibition	7.01	pIC50
Akt inhibitor VIII	Negative	6.68	pIC50
PHT-427	Inhibition	5.57	pKi
oridonin	Inhibition	5.05	pIC50

Binding affinities (BindingDB)

617 measured of 629 human assays (629 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-{5-[(2S)-2-amino-3-(1H-indol-3-yl)propoxy]pyridin-3-yl}-3-methyl-1H-indazole	IC50	0.16 nM
3-amino-3-[4-[1-(difluoromethyl)-8-phenyl-[1,2,4]triazolo[4,3-a][1,5]naphthyridin-7-yl]phenyl]-1-methylcyclobutan-1-ol	IC50	0.38 nM	US-8536193: Inhibitors of AKT activity
3-amino-1-methyl-3-[4-[3-phenyl-9-(1H-pyrazol-5-yl)-5H-imidazo[1,2-c][1,3]benzoxazin-2-yl]phenyl]cyclobutan-1-ol	IC50	0.8 nM	US-8772283: Imidazo-oxazine compound or salt thereof
3-amino-1-methyl-3-[4-[3-phenyl-9-(1H-pyrazol-4-yl)-5H-imidazo[1,2-c][1,3]benzoxazin-2-yl]phenyl]cyclobutan-1-ol	IC50	1.3 nM	US-8772283: Imidazo-oxazine compound or salt thereof
2-[4-(1-amino-3-hydroxy-3-methylcyclobutyl)phenyl]-3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazine-8-carboxamide	IC50	1.3 nM	US-8772283: Imidazo-oxazine compound or salt thereof
3-amino-1-cyclopropyl-3-[4-(5-phenyl-8-oxa-3,6,10-triazatricyclo[7.4.0.02,6]trideca-1(9),2,4,10,12-pentaen-4-yl)phenyl]cyclobutan-1-ol	IC50	1.4 nM	US-8772283: Imidazo-oxazine compound or salt thereof
3-amino-1-methyl-3-[4-(5-phenyl-8-oxa-3,6,10-triazatricyclo[7.4.0.02,6]trideca-1(9),2,4,10,12-pentaen-4-yl)phenyl]cyclobutan-1-ol	IC50	1.4 nM	US-8772283: Imidazo-oxazine compound or salt thereof
2-[4-(1-amino-3-hydroxy-3-methylcyclobutyl)phenyl]-N-methyl-3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazine-9-carboxamide	IC50	1.5 nM	US-8772283: Imidazo-oxazine compound or salt thereof
3-amino-1-cyclopropyl-3-[4-(5-phenyl-8-oxa-3,6,11-triazatricyclo[7.4.0.02,6]trideca-1(9),2,4,10,12-pentaen-4-yl)phenyl]cyclobutan-1-ol	IC50	1.6 nM	US-8772283: Imidazo-oxazine compound or salt thereof
2-[4-(1-amino-3-hydroxy-3-methylcyclobutyl)phenyl]-3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazine-9-carboxamide	IC50	1.6 nM	US-8772283: Imidazo-oxazine compound or salt thereof
Staurosporine	KD	1.7 nM
3-amino-1-cyclopropyl-3-[4-(9-methoxy-3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazin-2-yl)phenyl]cyclobutan-1-ol	IC50	1.8 nM	US-8772283: Imidazo-oxazine compound or salt thereof
2-[4-(1-amino-3-hydroxy-3-methylcyclobutyl)phenyl]-N-ethyl-3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazine-9-carboxamide	IC50	1.8 nM	US-8772283: Imidazo-oxazine compound or salt thereof
2-[4-(1-amino-3-hydroxy-3-methylcyclobutyl)phenyl]-N-methyl-3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazine-8-carboxamide	IC50	1.8 nM	US-8772283: Imidazo-oxazine compound or salt thereof
2-[4-(1-amino-3-hydroxy-3-methylcyclobutyl)phenyl]-N-ethoxy-3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazine-9-carboxamide	IC50	1.8 nM	US-8772283: Imidazo-oxazine compound or salt thereof
3-amino-1-methyl-3-[4-(5-phenyl-8-oxa-3,6,11-triazatricyclo[7.4.0.02,6]trideca-1(9),2,4,10,12-pentaen-4-yl)phenyl]cyclobutan-1-ol	IC50	2 nM	US-8772283: Imidazo-oxazine compound or salt thereof
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-7-(2-aminoethoxy)-1-ethyl-1H-imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	IC50	2 nM
2-[4-(1-amino-3-hydroxy-3-methylcyclobutyl)phenyl]-N-ethoxy-3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazine-8-carboxamide	IC50	2.1 nM	US-8772283: Imidazo-oxazine compound or salt thereof
3-amino-3-[4-[9-(hydroxymethyl)-3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazin-2-yl]phenyl]-1-methylcyclobutan-1-ol	IC50	2.2 nM	US-8772283: Imidazo-oxazine compound or salt thereof
1-[4-[5-(benzenecarboximidoyl)-6-imino-3-phenyl-1,5-naphthyridin-2-yl]phenyl]cyclobutan-1-amine	IC50	2.3 nM	US-8536193: Inhibitors of AKT activity
3-amino-1-cyclopropyl-3-[4-(7-fluoro-3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazin-2-yl)phenyl]cyclobutan-1-ol	IC50	2.3 nM	US-8772283: Imidazo-oxazine compound or salt thereof
2-[4-(1-amino-3-hydroxy-3-methylcyclobutyl)phenyl]-N-(2-hydroxyethyl)-3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazine-9-carboxamide	IC50	2.4 nM	US-8772283: Imidazo-oxazine compound or salt thereof
1-[2-[4-(1-aminocyclobutyl)phenyl]-8-methoxy-3-phenylimidazo[1,2-b]pyridazin-6-yl]ethanone	IC50	2.6 nM	US-9604989: Imidazopyridazines as Akt kinase inhibitors
3-amino-3-[4-(9-methoxy-3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazin-2-yl)phenyl]-1-methylcyclobutan-1-ol	IC50	2.9 nM	US-8772283: Imidazo-oxazine compound or salt thereof
6-(2-fluorophenyl)-7-[4-[[4-[3-(6-methyl-2-pyridinyl)-1H-1,2,4-triazol-5-yl]piperidin-1-yl]methyl]phenyl]imidazo[1,2-a]pyrimidine	IC50	3 nM	US-8957064: Fused pyrimidines
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-7-[(3S)-3-amino-4-phenylbutoxy]-1-ethyl-1H-imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	IC50	3 nM
(2S)-3-[(3-{[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-4-(3-hydroxy-3-methylbut-1-yn-1-yl)-1H-imidazo[4,5-c]pyridin-7-yl]oxy}propyl)amino]propane-1,2-diol	IC50	3 nM
2-[4-(1-amino-3-hydroxy-3-methylcyclobutyl)phenyl]-N-(2-hydroxyethyl)-3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazine-8-carboxamide	IC50	3.1 nM	US-8772283: Imidazo-oxazine compound or salt thereof
2-[4-(1,3-dihydroxy-3-methylcyclobutyl)phenyl]-3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazine-8-carboxylic acid	IC50	3.1 nM	US-8772283: Imidazo-oxazine compound or salt thereof
2-[4-(1-aminocyclobutyl)phenyl]-N-methyl-3-phenyl-8-(1H-pyrazol-5-yl)imidazo[1,2-b]pyridazine-6-carboxamide	IC50	3.1 nM	US-9604989: Imidazopyridazines as Akt kinase inhibitors
3-amino-1-cyclopropyl-3-[4-(10-fluoro-3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazin-2-yl)phenyl]cyclobutan-1-ol	IC50	3.7 nM	US-8772283: Imidazo-oxazine compound or salt thereof
3-amino-1-cyclopropyl-3-[4-(8-methoxy-3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazin-2-yl)phenyl]cyclobutan-1-ol	IC50	3.7 nM	US-8772283: Imidazo-oxazine compound or salt thereof
2-{5-[1-({4-[2-(methylsulfanyl)-6-phenylpyrido[2,3-d]pyrimidin-7-yl]phenyl}methyl)piperidin-4-yl]-4H-1,2,4-triazol-3-yl}pyridine	IC50	3.8 nM
3-amino-1-cyclopropyl-3-[4-(3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazin-2-yl)phenyl]cyclobutan-1-ol	IC50	3.9 nM	US-8772283: Imidazo-oxazine compound or salt thereof
1-[4-(5-phenyl-8-oxa-3,6,10-triazatricyclo[7.4.0.02,6]trideca-1(9),2,4,10,12-pentaen-4-yl)phenyl]cyclobutan-1-amine	IC50	3.9 nM	US-8772283: Imidazo-oxazine compound or salt thereof
1-[4-(6,8-dimethoxy-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutan-1-amine	IC50	3.9 nM	US-9604989: Imidazopyridazines as Akt kinase inhibitors
2-[4-(1-aminocyclobutyl)phenyl]-3-phenylimidazo[1,2-b]pyridazine-6,8-dicarboxamide	IC50	3.9 nM	US-9604989: Imidazopyridazines as Akt kinase inhibitors
2-[1-[[4-(6-phenylimidazo[1,2-a]pyrimidin-7-yl)phenyl]methyl]piperidin-4-yl]quinoxaline	IC50	4 nM	US-8957064: Fused pyrimidines
3-bromo-2-methyl-6-phenyl-7-[4-[[3-(3-pyridin-2-yl-1H-1,2,4-triazol-5-yl)azetidin-1-yl]methyl]phenyl]imidazo[1,2-a]pyrimidine	IC50	4 nM	US-8957064: Fused pyrimidines
methyl 3-[6-[4-(1-aminocyclobutyl)phenyl]-7-phenylimidazo[1,2-b]pyridazin-3-yl]benzoate	IC50	4 nM	US-8987273: Substituted imidazo[1,2-B]pyridazines
1-[1-({4-[2-(methylsulfanyl)-6-phenylpyrido[2,3-d]pyrimidin-7-yl]phenyl}methyl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine	IC50	4 nM
2-[4-(1-aminocyclobutyl)phenyl]-8-ethoxy-3-phenylimidazo[1,2-b]pyridazine-6-carboxamide	IC50	4.1 nM	US-9604989: Imidazopyridazines as Akt kinase inhibitors
3-amino-1-ethyl-3-[4-(5-phenyl-8-oxa-3,6,12-triazatricyclo[7.4.0.02,6]trideca-1(9),2,4,10,12-pentaen-4-yl)phenyl]cyclobutan-1-ol	IC50	4.2 nM	US-8772283: Imidazo-oxazine compound or salt thereof
1-[4-(6-methoxy-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutan-1-amine	IC50	4.2 nM	US-9604989: Imidazopyridazines as Akt kinase inhibitors
1-[4-[6-methoxy-3-phenyl-8-(1H-pyrazol-5-yl)imidazo[1,2-b]pyridazin-2-yl]phenyl]cyclobutan-1-amine	IC50	4.3 nM	US-9604989: Imidazopyridazines as Akt kinase inhibitors
2-[4-(1-amino-3-hydroxy-3-methylcyclobutyl)phenyl]-3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazine-9-carbonitrile	IC50	4.4 nM	US-8772283: Imidazo-oxazine compound or salt thereof
2-[4-(1-amino-3-hydroxy-3-methylcyclobutyl)phenyl]-N,N-dimethyl-3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazine-9-carboxamide	IC50	4.4 nM	US-8772283: Imidazo-oxazine compound or salt thereof
1-[4-[6-methoxy-3-phenyl-8-(1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-2-yl]phenyl]cyclobutan-1-amine	IC50	4.4 nM	US-9604989: Imidazopyridazines as Akt kinase inhibitors
4-{3-[1-({4-[2-(methylsulfanyl)-6-phenylpyrido[2,3-d]pyrimidin-7-yl]phenyl}methyl)piperidin-4-yl]-1H-pyrazol-5-yl}pyridine	IC50	4.5 nM
3-amino-3-[4-(10-fluoro-3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazin-2-yl)phenyl]-1-methylcyclobutan-1-ol	IC50	4.6 nM	US-8772283: Imidazo-oxazine compound or salt thereof

ChEMBL bioactivities

1824 potent at pChembl≥5 of 1888 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	IC50	0.2	nM	CHEMBL4440965
9.70	IC50	0.2	nM	Borussertib
9.59	IC50	0.26	nM	CHEMBL3701767
9.57	IC50	0.27	nM	CHEMBL3701740
9.55	IC50	0.28	nM	CHEMBL3701766
9.54	IC50	0.29	nM	CHEMBL3701717
9.52	IC50	0.3	nM	CHEMBL3701737
9.52	IC50	0.3	nM	CHEMBL5426352
9.51	IC50	0.31	nM	CHEMBL3701769
9.49	IC50	0.32	nM	CHEMBL3701762
9.46	IC50	0.35	nM	CHEMBL3701732
9.40	IC50	0.4	nM	CHEMBL3701776
9.40	IC50	0.4	nM	CHEMBL3701775
9.38	IC50	0.42	nM	CHEMBL3701763
9.32	IC50	0.48	nM	CHEMBL3701749
9.31	IC50	0.49	nM	CHEMBL3701770
9.30	IC50	0.5	nM	CHEMBL3701718
9.28	IC50	0.53	nM	CHEMBL3701773
9.27	IC50	0.54	nM	CHEMBL4441825
9.26	IC50	0.55	nM	CHEMBL3701758
9.24	IC50	0.57	nM	CHEMBL3701774
9.22	IC50	0.6	nM	CHEMBL3701734
9.20	Ki	0.63	nM	CHEMBL523586
9.15	IC50	0.7	nM	CHEMBL3701772
9.15	IC50	0.71	nM	CHEMBL3701720
9.13	IC50	0.74	nM	CHEMBL3701750
9.12	IC50	0.75	nM	CHEMBL3701735
9.11	IC50	0.78	nM	CHEMBL5316198
9.09	IC50	0.81	nM	VEVORISERTIB
9.07	IC50	0.85	nM	CHEMBL5316199
9.05	IC50	0.9	nM	CHEMBL5414256
9.04	IC50	0.91	nM	CHEMBL3701722
9.04	IC50	0.91	nM	CHEMBL3701721
9.04	IC50	0.91	nM	CHEMBL3701736
9.04	IC50	0.91	nM	CHEMBL3701752
9.04	IC50	0.91	nM	CHEMBL3701777
9.03	IC50	0.94	nM	CHEMBL3701778
9.01	IC50	0.97	nM	CHEMBL3701761
9.01	IC50	0.97	nM	CHEMBL3701753
9.00	IC50	1	nM	CHEMBL3701724
9.00	IC50	1	nM	CHEMBL3701727
9.00	IC50	1	nM	UPROSERTIB
9.00	IC50	1	nM	CHEMBL3919089
9.00	IC50	1	nM	CHEMBL5406950
9.00	IC50	1	nM	CHEMBL5402470
9.00	Ki	1	nM	CHEMBL1099297
8.96	IC50	1.1	nM	CHEMBL3701747
8.96	IC50	1.1	nM	CHEMBL3701765
8.96	IC50	1.1	nM	CHEMBL3701723
8.96	IC50	1.1	nM	CHEMBL3701751

PubChem BioAssay actives

963 with measured affinity, of 3628 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[2-oxo-3-[1-[[4-(5-oxo-3-phenyl-6H-1,6-naphthyridin-2-yl)phenyl]methyl]piperidin-4-yl]-1H-benzimidazol-5-yl]prop-2-enamide	1866987: Inhibition of AKT (unknown origin)	ic50	0.0002	uM
5-chloro-4-(4-chloro-1-methylpyrazol-5-yl)-N-[(3S,4S,6S)-4-(3,4-difluorophenyl)-6-[2-(methylamino)-2-oxoethyl]piperidin-3-yl]furan-2-carboxamide	1770730: Inhibition of N-terminal GST-tagged human AKT2 (120 to 481 residues) expressed in baculovirus infected Sf21 cells incubated for 1 hr in presence of ATP by mobility shift assay	ic50	0.0002	uM
2-[[(1R)-1-(3-fluoro-7-methyl-4-oxo-2-piperidin-1-ylpyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoic acid	2035284: Inhibition of AKT phosphorylation in human T47D cells harboring PI3Kalpha H1047R mutant incubated for 24 hrs by AlphaLISA assay	ic50	0.0003	uM
(2S)-1-(1H-indol-3-yl)-3-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]propan-2-amine	1797358: PKB In Vitro Enzyme Assay from Article 10.1016/j.jmb.2007.01.004: “A structural comparison of inhibitor binding to PKB, PKA and PKA-PKB chimera.”	ic50	0.0005	uM
5-chloro-4-(4-chloro-1-methylpyrazol-5-yl)-N-[(3S,4S,6S)-4-(3,4-difluorophenyl)-6-(2-hydroxyethyl)piperidin-3-yl]furan-2-carboxamide	1608039: Inhibition of human Akt2 by mobile shift assay	ic50	0.0005	uM
5-chloro-4-(4-chloro-1-methylpyrazol-5-yl)-N-[(3S,4S)-4-(3,4-difluorophenyl)piperidin-3-yl]furan-2-carboxamide;(2R,3R)-2,3-dihydroxybutanedioic acid	1608039: Inhibition of human Akt2 by mobile shift assay	ic50	0.0006	uM
N-[(2S)-1-amino-3-(3-fluorophenyl)propan-2-yl]-4-bromo-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)thiophene-2-carboxamide	417620: Inhibition of AKT2	ki	0.0006	uM
N-[1-[3-[3-[4-(1-aminocyclobutyl)phenyl]-2-(2-amino-3-pyridinyl)imidazo[4,5-b]pyridin-5-yl]phenyl]piperidin-4-yl]-N-methylacetamide	1922444: Inhibition of AKT2 (unknown origin)	ic50	0.0008	uM
2-[[(1R)-1-(3-cyano-7-methyl-4-oxo-2-piperidin-1-ylpyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoic acid	2035284: Inhibition of AKT phosphorylation in human T47D cells harboring PI3Kalpha H1047R mutant incubated for 24 hrs by AlphaLISA assay	ic50	0.0009	uM
6-[4-[1-[2-(azetidin-1-yl)ethyl]-4-[4-fluoro-3-(trifluoromethyl)phenyl]imidazol-2-yl]piperidin-1-yl]-5-chloropyrimidin-4-amine	1766232: Inhibition of Akt (unknown origin)	ic50	0.0010	uM
2-[[(1R)-1-[3-cyano-2-(4,4-difluoropiperidin-1-yl)-7-methyl-4-oxopyrido[1,2-a]pyrimidin-9-yl]ethyl]amino]benzoic acid	2035284: Inhibition of AKT phosphorylation in human T47D cells harboring PI3Kalpha H1047R mutant incubated for 24 hrs by AlphaLISA assay	ic50	0.0010	uM
2-[[(1R)-1-[3-cyano-2-(4,4-dimethylpiperidin-1-yl)-7-methyl-4-oxopyrido[1,2-a]pyrimidin-9-yl]ethyl]amino]benzoic acid	2035284: Inhibition of AKT phosphorylation in human T47D cells harboring PI3Kalpha H1047R mutant incubated for 24 hrs by AlphaLISA assay	ic50	0.0010	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-6-[(1S)-3-amino-1-phenylpropoxy]-1-ethylimidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	477361: Inhibition of AKT2	ki	0.0010	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	2151316: Inhibition of AKT2 (unknown origin) in the presence of [33P]ATP by kinase hotspot assay	ic50	0.0010	uM
N-[(2S)-1-amino-3-(3,4-difluorophenyl)propan-2-yl]-5-chloro-4-(4-chloro-1-methylpyrazol-5-yl)furan-2-carboxamide	1608039: Inhibition of human Akt2 by mobile shift assay	ic50	0.0010	uM
(4S)-5-[(1S,6R)-5-[(2S)-2-(4-chlorophenyl)-3-(propan-2-ylamino)propanoyl]-2,5-diazabicyclo[4.1.0]heptan-2-yl]-4-methyl-1,4-dihydropyrimido[4,5-d][1,3]oxazin-2-one	1912110: Inhibition of recombinant AKT2 (120 to 481 end residues) (unknown origin) catalytic domain expressed in Sf21 cells using peptide substrate incubated for 1 hr in presence of ATP by caliper off-chip mobility shift assay	ic50	0.0012	uM
2-iodo-N-[2-(4-nitroanilino)-2-oxo-1-phenylethyl]-N-phenylbenzamide	1687404: Inhibition of human AKT assessed as inhibition of substrate phosphorylation using AKTide-2T as substrate	ic50	0.0013	uM
4-[[(1S)-2-(azetidin-1-yl)-1-[4-chloro-3-(trifluoromethyl)phenyl]ethyl]amino]quinazoline-8-carboxylic acid	1766232: Inhibition of Akt (unknown origin)	ic50	0.0014	uM
3-[3-[4-(1-aminocyclobutyl)phenyl]-5-phenylimidazo[4,5-b]pyridin-2-yl]pyridin-2-amine	1917723: Inhibition of AKT2 (unknown origin) preincubated for 20 mins followed by [33P]-ATP addition measured after 120 mins by hotspot kinase assay	ic50	0.0014	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-6-[(2R)-2-amino-3-phenylpropoxy]-1-ethylimidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	477361: Inhibition of AKT2	ki	0.0020	uM
2-[[(1R)-1-[3-cyano-2-(3,3-difluoroazetidin-1-yl)-7-methyl-4-oxopyrido[1,2-a]pyrimidin-9-yl]ethyl]amino]benzoic acid	2035284: Inhibition of AKT phosphorylation in human T47D cells harboring PI3Kalpha H1047R mutant incubated for 24 hrs by AlphaLISA assay	ic50	0.0020	uM
N-[(2S)-1-amino-3-(4-fluorophenyl)propan-2-yl]-4-bromo-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)thiophene-2-carboxamide	417620: Inhibition of AKT2	ki	0.0020	uM
N-[(2S)-1-amino-3-(3-fluorophenyl)propan-2-yl]-5-chloro-4-(4-chloro-1-methylpyrazol-5-yl)thiophene-2-carboxamide	1922467: Inhibition of AKT2 (unknown origin) using Sox-AKT-tide as substrate by continuous real time fluorescence detection based [gamma33P]ATP assay	ic50	0.0020	uM
2-[benzyl-(2-phenylacetyl)amino]-N-(4-nitrophenyl)-2-phenylacetamide	1687404: Inhibition of human AKT assessed as inhibition of substrate phosphorylation using AKTide-2T as substrate	ic50	0.0021	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	624839: Binding constant for AKT2 kinase domain	kd	0.0021	uM
4-amino-N-[(4-chlorophenyl)methyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide	457046: Inhibition of PKBbeta by radiometric filter binding assay	ic50	0.0022	uM
4-amino-6-[4-[1-[2-(azetidin-1-yl)ethyl]-4-[4-fluoro-3-(trifluoromethyl)phenyl]imidazol-2-yl]piperidin-1-yl]pyrimidine-5-carbonitrile	1766232: Inhibition of Akt (unknown origin)	ic50	0.0022	uM
3-[3-[4-(1-aminocyclobutyl)phenyl]-5-pyridin-3-ylimidazo[4,5-b]pyridin-2-yl]pyridin-2-amine;hydrochloride	1636014: Inhibition of full length unphosphorylated AKT2 (1 to 481 residues) (unknown origin) expressed in baculovirus infected Sf9 insect cells using biotin-GRPRTSSFAEG as substrate preincubated for 20 mins followed by substrate addition measured after 30 mins by Alphascreen assay	ic50	0.0025	uM
5-(4-bromo-1-methylpyrazol-5-yl)-2-[(3S,4S)-4-(3,4-difluorophenyl)piperidin-3-yl]-3H-isoindol-1-one	2000394: Inhibition of AKT2 (unknown origin)	ic50	0.0027	uM
3-[3-[4-(1-aminocyclobutyl)phenyl]-5-(3-aminophenyl)imidazo[4,5-b]pyridin-2-yl]pyridin-2-amine;hydrochloride	1636011: Inhibition of full length active AKT2 (1 to 481 residues) (unknown origin) expressed in baculovirus infected Sf9 insect cells using biotin-GRPRTSSFAEG as substrate preincubated for 20 mins followed by substrate/PDK1/MAPKAPK2/DOPS/DOPC/PtdIns(3,4,5)P3 addition measured after 30 mins by Alphascreen assay	ic50	0.0028	uM
9-phenyl-8-[4-[[4-(4-pyridin-2-ylimidazol-1-yl)piperidin-1-yl]methyl]phenyl]-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3-amine	370681: Inhibition of human cloned Akt2 expressed in Drosophila S2 cells by HTRF assay	ic50	0.0028	uM
N-[[5-[(1Z)-1-[5-(carbamoylamino)-2-oxo-1H-indol-3-ylidene]ethyl]-1H-pyrrol-3-yl]methyl]-3-piperidin-1-ylpropanamide	291126: Inhibition of AKT2	ic50	0.0030	uM
2-[[(1R)-1-[2-(4,4-dimethylpiperidin-1-yl)-3,6-dimethyl-4-oxochromen-8-yl]ethyl]amino]benzoic acid	2035284: Inhibition of AKT phosphorylation in human T47D cells harboring PI3Kalpha H1047R mutant incubated for 24 hrs by AlphaLISA assay	ic50	0.0030	uM
2-[[(1R)-1-[3-cyano-2-(4,4-difluorocyclohexyl)-7-methyl-4-oxopyrido[1,2-a]pyrimidin-9-yl]ethyl]amino]benzoic acid	2035284: Inhibition of AKT phosphorylation in human T47D cells harboring PI3Kalpha H1047R mutant incubated for 24 hrs by AlphaLISA assay	ic50	0.0030	uM
2-[[(1R)-1-(3,7-dimethyl-4-oxo-2-piperidin-1-ylpyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoic acid	2035284: Inhibition of AKT phosphorylation in human T47D cells harboring PI3Kalpha H1047R mutant incubated for 24 hrs by AlphaLISA assay	ic50	0.0030	uM
2-[[(1R)-1-(3-cyano-7-methyl-4-oxo-2-pyrrolidin-1-ylpyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoic acid	2035284: Inhibition of AKT phosphorylation in human T47D cells harboring PI3Kalpha H1047R mutant incubated for 24 hrs by AlphaLISA assay	ic50	0.0030	uM
2-[[(1R)-1-[3-cyano-2-(6,6-difluoro-3-azabicyclo[3.1.1]heptan-3-yl)-7-methyl-4-oxopyrido[1,2-a]pyrimidin-9-yl]ethyl]amino]benzoic acid	2035284: Inhibition of AKT phosphorylation in human T47D cells harboring PI3Kalpha H1047R mutant incubated for 24 hrs by AlphaLISA assay	ic50	0.0030	uM
[(3Z)-3-[[4-[3-(aminomethyl)phenyl]-1H-pyrrol-2-yl]methylidene]-2-oxo-1H-indol-5-yl]urea	291126: Inhibition of AKT2	ic50	0.0030	uM
N-[(2S)-1-amino-3-phenylpropan-2-yl]-4-bromo-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)thiophene-2-carboxamide	417620: Inhibition of AKT2	ki	0.0030	uM
[4-[(4-chlorophenyl)methyl]-1-(7H-purin-6-yl)piperidin-4-yl]methanamine	327087: Inhibition of PKBbeta recombinant by radiometric filter binding assay	ic50	0.0030	uM
Capivasertib	2083100: Inhibition of AKT phosphorylation in human MDA-MB-231 incubated for 18 hrs by Western blot analysis	ic50	0.0030	uM
(2S)-3-(cyclopropylmethylamino)-2-[3-fluoro-4-(trifluoromethyl)phenyl]-1-[4-[(5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl]piperazin-1-yl]propan-1-one	708169: Competitive inhibition of wild-type full-length amino-terminal polyhistidine-tagged human Akt2 expressed in recombinant baculovirus system using fluorescence labeled substrate after 60 mins by fluorescence polarization assay in presence of ATP	ic50	0.0030	uM
1-[2-[11-[3-[3-[3-[4-(1-aminocyclobutyl)phenyl]-2-(2-amino-3-pyridinyl)imidazo[4,5-b]pyridin-5-yl]phenyl]propanoylamino]undecanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide	2073992: Inhibition of AKT in human SW620 cells	ic50	0.0031	uM
N-[3-[3-[4-(1-aminocyclobutyl)phenyl]-2-(2-amino-3-pyridinyl)imidazo[4,5-b]pyridin-5-yl]phenyl]acetamide;hydrochloride	1636011: Inhibition of full length active AKT2 (1 to 481 residues) (unknown origin) expressed in baculovirus infected Sf9 insect cells using biotin-GRPRTSSFAEG as substrate preincubated for 20 mins followed by substrate/PDK1/MAPKAPK2/DOPS/DOPC/PtdIns(3,4,5)P3 addition measured after 30 mins by Alphascreen assay	ic50	0.0032	uM
(2S)-2-(4-chlorophenyl)-1-[4-[(5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl]piperazin-1-yl]-3-(propan-2-ylamino)propan-1-one	1770730: Inhibition of N-terminal GST-tagged human AKT2 (120 to 481 residues) expressed in baculovirus infected Sf21 cells incubated for 1 hr in presence of ATP by mobility shift assay	ic50	0.0038	uM
N-[[5-[(1Z)-1-[5-(carbamoylamino)-2-oxo-1H-indol-3-ylidene]ethyl]-1H-pyrrol-3-yl]methyl]-1-methylpiperidine-4-carboxamide	291126: Inhibition of AKT2	ic50	0.0040	uM
N,N-dimethyl-2-[4-[6-phenyl-7-[4-[[4-(3-pyridin-2-yl-1H-1,2,4-triazol-5-yl)piperidin-1-yl]methyl]phenyl]pyrido[2,3-d]pyrimidin-2-yl]piperazin-1-yl]ethanamine	343895: Inhibition of Akt2	ic50	0.0040	uM
6-[4-[1-[2-(azetidin-1-yl)ethyl]-4-[4-fluoro-3-(trifluoromethyl)phenyl]imidazol-2-yl]piperidin-1-yl]-5-ethylpyrimidin-4-amine	1766232: Inhibition of Akt (unknown origin)	ic50	0.0040	uM
3-[5-[(Z)-[5-(carbamoylamino)-2-oxo-1H-indol-3-ylidene]methyl]-1H-pyrrol-3-yl]-N-[2-(dimethylamino)ethyl]benzamide	291126: Inhibition of AKT2	ic50	0.0040	uM
3-[5-[(Z)-[5-(carbamoylamino)-2-oxo-1H-indol-3-ylidene]methyl]-1H-pyrrol-3-yl]-N-(2-piperidin-1-ylethyl)benzamide	291126: Inhibition of AKT2	ic50	0.0040	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, affects expression	7
bisphenol A	increases phosphorylation, decreases expression, decreases methylation, decreases phosphorylation, increases expression	5
sodium arsenite	increases expression, decreases expression, decreases methylation, increases abundance	4
Ozone	affects cotreatment, affects expression, decreases expression, increases abundance	4
Resveratrol	increases expression, decreases expression, affects cotreatment, decreases phosphorylation, affects expression (+1 more)	3
Air Pollutants	affects cotreatment, affects expression, increases abundance, decreases methylation, increases expression	3
Copper	decreases phosphorylation, affects binding, decreases expression, affects cotreatment	3
Curcumin	decreases phosphorylation, decreases reaction, decreases expression, increases expression, increases phosphorylation	3
Oxygen	decreases phosphorylation, decreases expression, decreases reaction, increases expression, affects cotreatment	3
methacrylaldehyde	affects cotreatment, affects expression, decreases expression, increases abundance	2
Acrolein	affects cotreatment, affects expression, decreases expression, increases abundance	2
Doxorubicin	affects expression, affects cotreatment, affects response to substance	2
Hydrocortisone	decreases expression	2
Plant Extracts	increases expression, decreases expression, decreases reaction	2
Silicon Dioxide	increases phosphorylation, increases expression, decreases reaction	2
Cadmium Chloride	decreases reaction, increases abundance, increases phosphorylation, increases reaction	2
Genistein	decreases reaction, increases expression, decreases expression	2
Particulate Matter	decreases methylation, increases abundance, increases expression	2
GSK2110183	decreases activity	1
GSK2141795	decreases activity	1
pralsetinib	affects cotreatment, decreases phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, affects expression	1
methylselenic acid	decreases expression	1
nuciferine	affects cotreatment, decreases phosphorylation, decreases reaction	1
arsenite	increases expression	1
shikonin	decreases reaction, increases phosphorylation	1
afimoxifene	decreases response to substance	1
cobaltous chloride	affects cotreatment, decreases phosphorylation	1
butyraldehyde	decreases expression	1

ChEMBL screening assays

822 unique, capped per target: 802 binding, 19 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3881290	Binding	Inhibition of PKB-PIF (unknown origin) using AKTide-2T peptide substrate and [gamma33P]-ATP incubated for 20 mins by scintillation counting method	Compositions comprising (S)-2-amino-1-(4-chlorophenyl)-1-[4-(1H-pyrazol-4-yl)-phenyl]-ethanol as modulator of protein kinases
CHEMBL709030	Functional	Inhibition of Akt phosphorylation in LoVo cells	Synthesis and evaluation of 4-anilino-6,7-dialkoxy-3-quinolinecarbonitriles as inhibitors of kinases of the Ras-MAPK signaling cascade. — Bioorg Med Chem Lett
CHEMBL5353649	Toxicity	Inhibition of AKT2 (unknown origin)	Discovery of new macrophage M2 polarization modulators as multiple sclerosis treatment agents that enable the inflammation microenvironment remodeling. — Eur J Med Chem

Cellosaurus cell lines

12 cell lines: 10 cancer cell line, 1 transformed cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8B6	Abcam HCT 116 AKT2 KO	Cancer cell line	Male
CVCL_B8SA	Abcam MCF-7 AKT2 KO	Cancer cell line	Female
CVCL_B9D8	Abcam A-549 AKT2 KO	Cancer cell line	Male
CVCL_D7JY	Ubigene A-549 AKT2 KO	Cancer cell line	Male
CVCL_D8H9	Ubigene HCT 116 AKT2 KO	Cancer cell line	Male
CVCL_D8YZ	Ubigene HEK293 AKT2 KO	Transformed cell line	Female
CVCL_D9XI	Ubigene HeLa AKT2 KO	Cancer cell line	Female
CVCL_E4WS	ZR-75-1 AKT2 pool B	Cancer cell line	Female
CVCL_HD53	DLD-1 AKT2(-/-)	Cancer cell line	Male
CVCL_HD67	HCT 116 AKT2(-/-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00006163	PHASE4	COMPLETED	Computer-assisted Diabetes Self-management Interventions
NCT00036504	PHASE4	COMPLETED	Efficacy and Safety of Twice-Daily Insulin Lispro Low Mixture Compared to a Once-Daily Long Acting Insulin Comparator in Patients Who Have Been Using One or More Oral Antihyperglycemic Agents Without Insulin
NCT00044460	PHASE4	COMPLETED	Efficacy and Safety In Poorly Controlled Type 2 Diabetics
NCT00095446	PHASE4	COMPLETED	NovoLog Observation Trial in Subjects With Type 1 and Type 2 Diabetes
NCT00101751	PHASE4	COMPLETED	INITIATE Plus (INITiation of Insulin to Reach A1c TargEt) Study
NCT00110370	PHASE4	COMPLETED	Comparing Pre-Mixed Insulin With Insulin Glargine Combined With Rapid-Acting Insulin in Patients With Type 2 Diabetes
NCT00110448	PHASE4	COMPLETED	Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial
NCT00118950	PHASE4	COMPLETED	Effect of Metformin Versus Repaglinide Treatment in Non-Obese Type 2 Diabetic Patients Uncontrolled by Diet
NCT00118963	PHASE4	COMPLETED	Effect of Repaglinide Versus Metformin Treatment in Non-Obese Patients With Type-2-Diabetes
NCT00121966	PHASE4	COMPLETED	South Danish Diabetes Study: Evaluation of the Antidiabetic Treatment of Type 2 Diabetes Mellitus
NCT00123604	PHASE4	COMPLETED	Vascular Effects of Carvedilol Versus Metoprolol in Hypertensive Patients With Type 2 Diabetes
NCT00123643	PHASE4	COMPLETED	Vascular Effects of Rosiglitazone Versus Glyburide in Type 2 Diabetic Patients
NCT00124397	PHASE4	COMPLETED	Atorvastatin and Endothelial Function in Type 2 Diabetes Mellitus (ATTEND-Study)
NCT00129233	PHASE4	COMPLETED	Comparison of Valsartan With Amlodipine in Hypertensive Patients With Glucose Intolerance
NCT00133718	PHASE4	COMPLETED	A 2 Year Trial of Patients With Type 2 Diabetes Focusing on Cardiovascular Diagnostics and Metabolic Control
NCT00135070	PHASE4	TERMINATED	Hospital In-Patient Insulin Study
NCT00141232	PHASE4	COMPLETED	Evaluating Atorvastatin With Omega-3 Fatty Acids in Cardiovascular Risk Reduction in Patients With Type 2 Diabetes
NCT00144144	PHASE4	UNKNOWN	A Study on Ca Blocker Versus AII Antagonists in Hypertension With Type 2 Diabetes
NCT00149331	PHASE4	COMPLETED	The Effects of Two Education Strategies About Insulin on Patient Preferences and Perceptions About Insulin Therapy
NCT00162357	PHASE4	COMPLETED	Post-PCI:Cardiac Imaging in Patients With Diabetes to Detect Coronary Artery Blockages Previously Opened by Angioplasty
NCT00174681	PHASE4	COMPLETED	Tulip Study: Testing the Usefulness of Lantus When Initiated Prematurely In Patients With Type 2 Diabetes
NCT00174824	PHASE4	COMPLETED	Comparison of Insulin Glargine and NPH Human Insulin in Progression of Diabetic Retinopathy in Type 2 Diabetic Patients
NCT00177398	PHASE4	COMPLETED	Effect of Glargine Insulin on Glucose Control in Hospitalized Patients Who Receive Tube Feedings
NCT00179400	PHASE4	COMPLETED	The Role of Acute Combined PPAR Alpha and Gamma Stimulation on Insulin Action in Humans
NCT00184561	PHASE4	COMPLETED	Effectiveness and Safety of Biphasic Insulin Aspart 70/30 in Subjects With Type 2 Diabetes
NCT00184626	PHASE4	COMPLETED	Comparison of Insulin Glargine Versus Biphasic Insulin Aspart 30/70 or Biphasic Insulin Aspart 30/70 in Combination With Metformin in Subjects With Type 2 Diabetes.
NCT00191178	PHASE4	COMPLETED	Effects of Insulin in Perceived Mood Symptoms in Patients With Type 2 Diabetes
NCT00191282	PHASE4	COMPLETED	Hyperglycemia and Cardiovascular Outcomes With Type 2 Diabetes
NCT00191464	PHASE4	COMPLETED	Long-Term Effects of Insulin Plus Metformin Regimens on the Overall and Postprandial Glycemic Control of Patients With Type 2 Diabetes
NCT00192803	PHASE4	UNKNOWN	Non-Insulin Dependent Diabetes Mellitus (NIDDM) and Angiotensin Converting Enzyme 2 (ACE2): Diabetic Patients Treated With Antihypertensive Drugs
NCT00202033	PHASE4	COMPLETED	Impact of Self-Monitoring Blood Glucose Frequency on Glycemic Control in Patients With Type 2 Diabetes
NCT00205660	PHASE4	COMPLETED	Changes in Adiposity, Metabolic Measures From Atypicals to Aripiprazole
NCT00212290	PHASE4	COMPLETED	Insulin Resistance and Central Nervous System (CNS) Function in Type 2 Diabetes
NCT00212303	PHASE4	COMPLETED	Exercise Training in Type 2 Diabetes and Hypertension
NCT00225342	PHASE4	WITHDRAWN	Study Protocol for Rosiglitazone Versus Gliclazide in Diabetics With Angina
NCT00238472	PHASE4	COMPLETED	A Pilot Study to Evaluate the Effects of Nateglinide vs. Glibenclamide on Renal Hemodynamics and Albumin Excretion
NCT00239538	PHASE4	COMPLETED	SMOOTH - Blood Pressure Control in Diabetic/Obese Patients
NCT00240253	PHASE4	COMPLETED	A Study Evaluating the Efficacy and Safety of Adding Symlin® to Lantus® (Insulin Glargine) in Subjects With Type 2 Diabetes
NCT00240422	PHASE4	COMPLETED	Trial to Compare the Effects of Either Telmisartan (40-80 mg PO Once Daily) or Ramipril (5-10 mg PO Once Daily) on Renal Endothelial Dysfunction in Hypertensive Patients With Type 2 Diabetes
NCT00241085	PHASE4	COMPLETED	Effect of Valsartan on Proteinuria in Patients With Hypertension and Diabetes Mellitus