Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXGJ8N1)

• DOT Name: Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3)
• Synonyms: PI3-kinase regulatory subunit gamma; PI3K regulatory subunit gamma; PtdIns-3-kinase regulatory subunit gamma; Phosphatidylinositol 3-kinase 55 kDa regulatory subunit gamma; PI3-kinase subunit p55-gamma; PtdIns-3-kinase regulatory subunit p55-gamma; p55PIK
• Gene Name: PIK3R3
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Acute lymphocytic leukaemia
  Advanced cancer
  Alzheimer disease
  Benign prostatic hyperplasia
  Bone osteosarcoma
  Breast cancer
  Cervical cancer
  Cervical carcinoma
  Classic Hodgkin lymphoma
  Colorectal carcinoma
  Crohn disease
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Fatty liver disease
  Gastric cancer
  Glioma
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Multiple sclerosis
  Non-alcoholic fatty liver disease
  Non-small-cell lung cancer
  Osteoarthritis
  Osteosarcoma
  Ovarian neoplasm
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Rheumatoid arthritis
  Stomach cancer
  Systemic lupus erythematosus
  Triple negative breast cancer
  Ulcerative colitis
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
  Retinoblastoma
  Type-1 diabetes
  Adult glioblastoma
  Glioblastoma multiforme
  Melanoma
  Nervous system disease
  Pneumonia
  Acute myelogenous leukaemia
  Arthritis
  Neoplasm
  Ovarian cancer
• UniProt ID: P55G_HUMAN
• Pfam ID: PF16454 ; PF00017
• Sequence:
  MYNTVWSMDRDDADWREVMMPYSTELIFYIEMDPPALPPKPPKPMTSAVPNGMKDSSVSL
  QDAEWYWGDISREEVNDKLRDMPDGTFLVRDASTKMQGDYTLTLRKGGNNKLIKIYHRDG
  KYGFSDPLTFNSVVELINHYHHESLAQYNPKLDVKLMYPVSRYQQDQLVKEDNIDAVGKK
  LQEYHSQYQEKSKEYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCHTQEQHSKEY
  IERFRREGNEKEIERIMMNYDKLKSRLGEIHDSKMRLEQDLKNQALDNREIDKKMNSIKP
  DLIQLRKIRDQHLVWLNHKGVRQKRLNVWLGIKNEDADENYFINEEDENLPHYDEKTWFV
  EDINRVQAEDLLYGKPDGAFLIRESSKKGCYACSVVADGEVKHCVIYSTARGYGFAEPYN
  LYSSLKELVLHYQQTSLVQHNDSLNVRLAYPVHAQMPSLCR
• Function: Binds to activated (phosphorylated) protein-tyrosine kinases through its SH2 domain and regulates their kinase activity. During insulin stimulation, it also binds to IRS-1.
• Tissue Specificity: Highest levels in brain and testis. Lower levels in adipose tissue, kidney, heart, lung and skeletal muscle.
• KEGG Pathway:
  EGFR tyrosine ki.se inhibitor resistance (hsa01521)
  Endocrine resistance (hsa01522)
  Platinum drug resistance (hsa01524)
  ErbB sig.ling pathway (hsa04012)
  Ras sig.ling pathway (hsa04014)
  Rap1 sig.ling pathway (hsa04015)
  cAMP sig.ling pathway (hsa04024)
  Chemokine sig.ling pathway (hsa04062)
  HIF-1 sig.ling pathway (hsa04066)
  FoxO sig.ling pathway (hsa04068)
  Phosphatidylinositol sig.ling system (hsa04070)
  Sphingolipid sig.ling pathway (hsa04071)
  Phospholipase D sig.ling pathway (hsa04072)
  Autophagy - animal (hsa04140)
  mTOR sig.ling pathway (hsa04150)
  PI3K-Akt sig.ling pathway (hsa04151)
  AMPK sig.ling pathway (hsa04152)
  Apoptosis (hsa04210)
  Longevity regulating pathway (hsa04211)
  Longevity regulating pathway - multiple species (hsa04213)
  Cellular senescence (hsa04218)
  Axon guidance (hsa04360)
  VEGF sig.ling pathway (hsa04370)
  Osteoclast differentiation (hsa04380)
  Focal adhesion (hsa04510)
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
  Platelet activation (hsa04611)
  Neutrophil extracellular trap formation (hsa04613)
  Toll-like receptor sig.ling pathway (hsa04620)
  C-type lectin receptor sig.ling pathway (hsa04625)
  JAK-STAT sig.ling pathway (hsa04630)
  .tural killer cell mediated cytotoxicity (hsa04650)
  T cell receptor sig.ling pathway (hsa04660)
  B cell receptor sig.ling pathway (hsa04662)
  Fc epsilon RI sig.ling pathway (hsa04664)
  Fc gamma R-mediated phagocytosis (hsa04666)
  TNF sig.ling pathway (hsa04668)
  Leukocyte transendothelial migration (hsa04670)
  Neurotrophin sig.ling pathway (hsa04722)
  Cholinergic sy.pse (hsa04725)
  Inflammatory mediator regulation of TRP channels (hsa04750)
  Regulation of actin cytoskeleton (hsa04810)
  Insulin sig.ling pathway (hsa04910)
  Progesterone-mediated oocyte maturation (hsa04914)
  Estrogen sig.ling pathway (hsa04915)
  Prolactin sig.ling pathway (hsa04917)
  Thyroid hormone sig.ling pathway (hsa04919)
  Regulation of lipolysis in adipocytes (hsa04923)
  Relaxin sig.ling pathway (hsa04926)
  GnRH secretion (hsa04929)
  Type II diabetes mellitus (hsa04930)
  Insulin resistance (hsa04931)
  Non-alcoholic fatty liver disease (hsa04932)
  AGE-RAGE sig.ling pathway in diabetic complications (hsa04933)
  Growth hormone synthesis, secretion and action (hsa04935)
  Aldosterone-regulated sodium reabsorption (hsa04960)
  Carbohydrate digestion and absorption (hsa04973)
  Alzheimer disease (hsa05010)
  Spinocerebellar ataxia (hsa05017)
  Prion disease (hsa05020)
  Bacterial invasion of epithelial cells (hsa05100)
  Shigellosis (hsa05131)
  Yersinia infection (hsa05135)
  Chagas disease (hsa05142)
  Amoebiasis (hsa05146)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Human cytomegalovirus infection (hsa05163)
  Influenza A (hsa05164)
  Human papillomavirus infection (hsa05165)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Herpes simplex virus 1 infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Human immunodeficiency virus 1 infection (hsa05170)
  Coro.virus disease - COVID-19 (hsa05171)
  Pathways in cancer (hsa05200)
  Viral carcinogenesis (hsa05203)
  Proteoglycans in cancer (hsa05205)
  MicroR.s in cancer (hsa05206)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Colorectal cancer (hsa05210)
  Re.l cell carcinoma (hsa05211)
  Pancreatic cancer (hsa05212)
  Endometrial cancer (hsa05213)
  Glioma (hsa05214)
  Prostate cancer (hsa05215)
  Melanoma (hsa05218)
  Chronic myeloid leukemia (hsa05220)
  Acute myeloid leukemia (hsa05221)
  Small cell lung cancer (hsa05222)
  Non-small cell lung cancer (hsa05223)
  Breast cancer (hsa05224)
  Hepatocellular carcinoma (hsa05225)
  Gastric cancer (hsa05226)
  Central carbon metabolism in cancer (hsa05230)
  Choline metabolism in cancer (hsa05231)
  PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235)
  Diabetic cardiomyopathy (hsa05415)
  Lipid and atherosclerosis (hsa05417)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  PIP3 activates AKT signaling (R-HSA-1257604)
  Interleukin-7 signaling (R-HSA-1266695)
  Signaling by SCF-KIT (R-HSA-1433557)
  Synthesis of PIPs at the plasma membrane (R-HSA-1660499)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  Costimulation by the CD28 family (R-HSA-388841)
  CD28 dependent PI3K/Akt signaling (R-HSA-389357)
  G alpha (q) signalling events (R-HSA-416476)
  Interleukin-3, Interleukin-5 and GM-CSF signaling (R-HSA-512988)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  RET signaling (R-HSA-8853659)
  Extra-nuclear estrogen signaling (R-HSA-9009391)
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC2 GTPase cycle (R-HSA-9013404)
  Interleukin receptor SHC signaling (R-HSA-912526)
  Regulation of signaling by CBL (R-HSA-912631)
  Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants (R-HSA-9670439)
  GPVI-mediated activation cascade (R-HSA-114604)
• BioCyc Pathway: MetaCyc:ENSG00000117461-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Definitive	Altered Expression	[1]
Atherosclerosis	DISMN9J3	Definitive	Altered Expression	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[5]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[7]
Cervical cancer	DISFSHPF	Strong	Biomarker	[8]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[8]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[10]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[11]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[12]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[13]
Fatty liver disease	DIS485QZ	Strong	Altered Expression	[14]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[15]
Glioma	DIS5RPEH	Strong	Biomarker	[16]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[17]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[18]
Lung cancer	DISCM4YA	Strong	Biomarker	[19]
Lung carcinoma	DISTR26C	Strong	Biomarker	[19]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[20]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[14]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[21]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[22]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[6]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[23]
Pancreatic cancer	DISJC981	Strong	Biomarker	[3]
Prostate cancer	DISF190Y	Strong	Biomarker	[24]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[24]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[25]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[15]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[26]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[27]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[11]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Altered Expression	[28]
Liver cancer	DISDE4BI	moderate	Altered Expression	[28]
Retinoblastoma	DISVPNPB	moderate	Biomarker	[18]
Type-1 diabetes	DIS7HLUB	moderate	Altered Expression	[29]
Adult glioblastoma	DISVP4LU	Disputed	Altered Expression	[30]
Glioblastoma multiforme	DISK8246	Disputed	Altered Expression	[30]
Melanoma	DIS1RRCY	Disputed	Biomarker	[31]
Nervous system disease	DISJ7GGT	Disputed	Biomarker	[32]
Pneumonia	DIS8EF3M	Disputed	Biomarker	[33]
Acute myelogenous leukaemia	DISCSPTN	Limited	Altered Expression	[34]
Arthritis	DIST1YEL	Limited	Genetic Variation	[35]
Neoplasm	DISZKGEW	Limited	Biomarker	[8]
Ovarian cancer	DISZJHAP	Limited	Altered Expression	[23]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3) increases the response to substance of Arsenic.	[63]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[36]

33 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[37]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[40]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[41]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[42]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[43]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[44]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[45]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[46]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[47]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[43]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[43]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[46]
DTI-015	DMXZRW0	Approved	DTI-015 increases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[48]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[49]
Estrone	DM5T6US	Approved	Estrone decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[43]
Mestranol	DMG3F94	Approved	Mestranol decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[43]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[50]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[51]
Resveratrol	DM3RWXL	Phase 3	Resveratrol affects the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[52]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[43]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[53]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[54]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[55]
HEXESTROL	DM9AGWQ	Withdrawn from market	HEXESTROL decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[43]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[56]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[57]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[58]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[59]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[60]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[61]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3).	[62]

References

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