Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTCWXC3)

• DOT Name: Son of sevenless homolog 1 (SOS1)
• Synonyms: SOS-1
• Gene Name: SOS1
• Related Disease:
  Noonan syndrome
  Noonan syndrome 4
  Aarskog-Scott syndrome, X-linked
  Acute myelogenous leukaemia
  Adult glioblastoma
  Alzheimer disease
  Artery stenosis
  Breast neoplasm
  Cardiomyopathy
  Cockayne syndrome
  Cornelia de Lange syndrome
  Corticobasal degeneration
  Cryptorchidism
  Dubowitz syndrome
  Fibromatosis, gingival, 1
  Glioma
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Hypertrophic cardiomyopathy
  Noonan syndrome 1
  Noonan syndrome 3
  Prader-Willi syndrome
  Prostate cancer
  Prostate carcinoma
  Robinow syndrome
  Schizophrenia
  Seckel syndrome
  Silver-Russell syndrome
  T-cell acute lymphoblastic leukaemia
  Adult lymphoma
  Amyotrophic lateral sclerosis
  Chronic myelomonocytic leukaemia
  Lymphoma
  Melanoma
  Pediatric lymphoma
  Ptosis
  Type-1/2 diabetes
  Ventricular septal defect
  Hereditary gingival fibromatosis
  Cardiofaciocutaneous syndrome
  Costello syndrome
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Epithelial ovarian cancer
  Glioblastoma multiforme
  Hermansky-Pudlak syndrome
  Lung adenocarcinoma
  Non-small-cell lung cancer
  Noonan syndrome with multiple lentigines
  Retinitis pigmentosa 3
• UniProt ID: SOS1_HUMAN
• PDB ID: 1AWE ; 1BKD ; 1DBH ; 1NVU ; 1NVV ; 1NVW ; 1NVX ; 1Q9C ; 1XD2 ; 1XD4 ; 1XDV ; 2II0 ; 3KSY ; 4NYI ; 4NYJ ; 4NYM ; 4URU ; 4URV ; 4URW ; 4URX ; 4URY ; 4URZ ; 4US0 ; 4US1 ; 4US2 ; 5OVD ; 5OVE ; 5OVF ; 5OVG ; 5OVH ; 5OVI ; 5WFO ; 5WFP ; 5WFQ ; 5WFR ; 6BVI ; 6BVJ ; 6BVK ; 6BVL ; 6BVM ; 6CUO ; 6CUP ; 6CUR ; 6D55 ; 6D56 ; 6D59 ; 6D5E ; 6D5G ; 6D5H ; 6D5J ; 6D5L ; 6D5M ; 6D5V ; 6D5W ; 6EPL ; 6EPM ; 6EPN ; 6EPO ; 6EPP ; 6F08 ; 6SCM ; 6SFR ; 6V94 ; 6V9F ; 6V9J ; 6V9L ; 6V9M ; 6V9N ; 6V9O ; 6Y44 ; 7AVI ; 7AVL ; 7AVS ; 7AVT ; 7AVU ; 7AVV ; 7KFZ ; 7UKR ; 7UKS ; 8BE2 ; 8BE4 ; 8BE5 ; 8BE6 ; 8BE7 ; 8BE8 ; 8BE9 ; 8BEA
• Pfam ID: PF00169 ; PF00617 ; PF00618 ; PF00621
• Sequence:
  MQAQQLPYEFFSEENAPKWRGLLVPALKKVQGQVHPTLESNDDALQYVEELILQLLNMLC
  QAQPRSASDVEERVQKSFPHPIDKWAIADAQSAIEKRKRRNPLSLPVEKIHPLLKEVLGY
  KIDHQVSVYIVAVLEYISADILKLVGNYVRNIRHYEITKQDIKVAMCADKVLMDMFHQDV
  EDINILSLTDEEPSTSGEQTYYDLVKAFMAEIRQYIRELNLIIKVFREPFVSNSKLFSAN
  DVENIFSRIVDIHELSVKLLGHIEDTVEMTDEGSPHPLVGSCFEDLAEELAFDPYESYAR
  DILRPGFHDRFLSQLSKPGAALYLQSIGEGFKEAVQYVLPRLLLAPVYHCLHYFELLKQL
  EEKSEDQEDKECLKQAITALLNVQSGMEKICSKSLAKRRLSESACRFYSQQMKGKQLAIK
  KMNEIQKNIDGWEGKDIGQCCNEFIMEGTLTRVGAKHERHIFLFDGLMICCKSNHGQPRL
  PGASNAEYRLKEKFFMRKVQINDKDDTNEYKHAFEIILKDENSVIFSAKSAEEKNNWMAA
  LISLQYRSTLERMLDVTMLQEEKEEQMRLPSADVYRFAEPDSEENIIFEENMQPKAGIPI
  IKAGTVIKLIERLTYHMYADPNFVRTFLTTYRSFCKPQELLSLIIERFEIPEPEPTEADR
  IAIENGDQPLSAELKRFRKEYIQPVQLRVLNVCRHWVEHHFYDFERDAYLLQRMEEFIGT
  VRGKAMKKWVESITKIIQRKKIARDNGPGHNITFQSSPPTVEWHISRPGHIETFDLLTLH
  PIEIARQLTLLESDLYRAVQPSELVGSVWTKEDKEINSPNLLKMIRHTTNLTLWFEKCIV
  ETENLEERVAVVSRIIEILQVFQELNNFNGVLEVVSAMNSSPVYRLDHTFEQIPSRQKKI
  LEEAHELSEDHYKKYLAKLRSINPPCVPFFGIYLTNILKTEEGNPEVLKRHGKELINFSK
  RRKVAEITGEIQQYQNQPYCLRVESDIKRFFENLNPMGNSMEKEFTDYLFNKSLEIEPRN
  PKPLPRFPKKYSYPLKSPGVRPSNPRPGTMRHPTPLQQEPRKISYSRIPESETESTASAP
  NSPRTPLTPPPASGASSTTDVCSVFDSDHSSPFHSSNDTVFIQVTLPHGPRSASVSSISL
  TKGTDEVPVPPPVPPRRRPESAPAESSPSKIMSKHLDSPPAIPPRQPTSKAYSPRYSISD
  RTSISDPPESPPLLPPREPVRTPDVFSSSPLHLQPPPLGKKSDHGNAFFPNSPSPFTPPP
  PQTPSPHGTRRHLPSPPLTQEVDLHSIAGPPVPPRQSTSQHIPKLPPKTYKREHTHPSMH
  RDGPPLLENAHSS
• Function: Promotes the exchange of Ras-bound GDP by GTP. Probably by promoting Ras activation, regulates phosphorylation of MAP kinase MAPK3 in response to EGF. Catalytic component of a trimeric complex that participates in transduction of signals from Ras to Rac by promoting the Rac-specific guanine nucleotide exchange factor (GEF) activity.
• Tissue Specificity: Expressed in gingival tissues.
• KEGG Pathway:
  EGFR tyrosine ki.se inhibitor resistance (hsa01521)
  Endocrine resistance (hsa01522)
  MAPK sig.ling pathway (hsa04010)
  ErbB sig.ling pathway (hsa04012)
  Ras sig.ling pathway (hsa04014)
  Chemokine sig.ling pathway (hsa04062)
  FoxO sig.ling pathway (hsa04068)
  Phospholipase D sig.ling pathway (hsa04072)
  mTOR sig.ling pathway (hsa04150)
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  Gap junction (hsa04540)
  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)
  Thermogenesis (hsa04714)
  Neurotrophin sig.ling pathway (hsa04722)
  Regulation of actin cytoskeleton (hsa04810)
  Insulin sig.ling pathway (hsa04910)
  GnRH sig.ling pathway (hsa04912)
  Estrogen sig.ling pathway (hsa04915)
  Prolactin sig.ling pathway (hsa04917)
  Relaxin sig.ling pathway (hsa04926)
  Growth hormone synthesis, secretion and action (hsa04935)
  Alcoholism (hsa05034)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Human cytomegalovirus infection (hsa05163)
  Human papillomavirus infection (hsa05165)
  Pathways in cancer (hsa05200)
  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)
  Endometrial cancer (hsa05213)
  Glioma (hsa05214)
  Prostate cancer (hsa05215)
  Chronic myeloid leukemia (hsa05220)
  Acute myeloid leukemia (hsa05221)
  Non-small cell lung cancer (hsa05223)
  Breast cancer (hsa05224)
  Hepatocellular carcinoma (hsa05225)
  Gastric cancer (hsa05226)
  Choline metabolism in cancer (hsa05231)
• Reactome Pathway:
  Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants (R-HSA-1236382)
  SHC1 events in ERBB2 signaling (R-HSA-1250196)
  SHC1 events in ERBB4 signaling (R-HSA-1250347)
  Signaling by SCF-KIT (R-HSA-1433557)
  Regulation of KIT signaling (R-HSA-1433559)
  Signalling to RAS (R-HSA-167044)
  GRB2 events in EGFR signaling (R-HSA-179812)
  SHC1 events in EGFR signaling (R-HSA-180336)
  Downstream signal transduction (R-HSA-186763)
  NRAGE signals death through JNK (R-HSA-193648)
  GRB2 events in ERBB2 signaling (R-HSA-1963640)
  Tie2 Signaling (R-HSA-210993)
  EGFR Transactivation by Gastrin (R-HSA-2179392)
  DAP12 signaling (R-HSA-2424491)
  SHC-related events triggered by IGF1R (R-HSA-2428933)
  Role of LAT2/NTAL/LAB on calcium mobilization (R-HSA-2730905)
  FCERI mediated MAPK activation (R-HSA-2871796)
  FCERI mediated Ca+2 mobilization (R-HSA-2871809)
  GRB2 (R-HSA-354194)
  NCAM signaling for neurite out-growth (R-HSA-375165)
  G alpha (12/13) signalling events (R-HSA-416482)
  Activation of RAC1 (R-HSA-428540)
  Constitutive Signaling by EGFRvIII (R-HSA-5637810)
  SHC-mediated cascade (R-HSA-5654688)
  FRS-mediated FGFR1 signaling (R-HSA-5654693)
  SHC-mediated cascade (R-HSA-5654699)
  FRS-mediated FGFR2 signaling (R-HSA-5654700)
  SHC-mediated cascade (R-HSA-5654704)
  FRS-mediated FGFR3 signaling (R-HSA-5654706)
  FRS-mediated FGFR4 signaling (R-HSA-5654712)
  SHC-mediated cascade (R-HSA-5654719)
  Signaling by FGFR2 in disease (R-HSA-5655253)
  Signaling by FGFR4 in disease (R-HSA-5655291)
  Signaling by FGFR1 in disease (R-HSA-5655302)
  Signaling by FGFR3 in disease (R-HSA-5655332)
  RAF/MAP kinase cascade (R-HSA-5673001)
  Signal attenuation (R-HSA-74749)
  Insulin receptor signalling cascade (R-HSA-74751)
  MET activates RAS signaling (R-HSA-8851805)
  RET signaling (R-HSA-8853659)
  Interleukin-15 signaling (R-HSA-8983432)
  RAC1 GTPase cycle (R-HSA-9013149)
  Activated NTRK2 signals through RAS (R-HSA-9026519)
  Erythropoietin activates RAS (R-HSA-9027284)
  Activated NTRK2 signals through FRS2 and FRS3 (R-HSA-9028731)
  Activated NTRK3 signals through RAS (R-HSA-9034864)
  Interleukin receptor SHC signaling (R-HSA-912526)
  FLT3 Signaling (R-HSA-9607240)
  Constitutive Signaling by Overexpressed ERBB2 (R-HSA-9634285)
  Signaling by ERBB2 KD Mutants (R-HSA-9664565)
  Signaling by ERBB2 ECD mutants (R-HSA-9665348)
  Signaling by ERBB2 TMD/JMD mutants (R-HSA-9665686)
  Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants (R-HSA-9670439)
  Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants (R-HSA-9673767)
  Signaling by PDGFRA extracellular domain mutants (R-HSA-9673770)
  Potential therapeutics for SARS (R-HSA-9679191)
  Signaling by CSF1 (M-CSF) in myeloid cells (R-HSA-9680350)
  Signaling by FLT3 fusion proteins (R-HSA-9703465)
  Signaling by FLT3 ITD and TKD mutants (R-HSA-9703648)
  Antigen activates B Cell Receptor (BCR) leading to generation of second messengers (R-HSA-983695)
  SOS-mediated signalling (R-HSA-112412)

Molecular Interaction Atlas (MIA) of This DOT

51 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Noonan syndrome	DIS7Q7DN	Definitive	Autosomal dominant	[1]
Noonan syndrome 4	DISW145E	Definitive	Autosomal dominant	[2]
Aarskog-Scott syndrome, X-linked	DISNHV62	Strong	Altered Expression	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[4]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Artery stenosis	DISQU4Q5	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Cardiomyopathy	DISUPZRG	Strong	Genetic Variation	[9]
Cockayne syndrome	DISW6GL2	Strong	Biomarker	[10]
Cornelia de Lange syndrome	DISEQSXO	Strong	Biomarker	[10]
Corticobasal degeneration	DISSMOTT	Strong	Genetic Variation	[11]
Cryptorchidism	DISYUD2P	Strong	Altered Expression	[12]
Dubowitz syndrome	DISRMNLQ	Strong	Biomarker	[10]
Fibromatosis, gingival, 1	DIS2TQ5E	Strong	Autosomal dominant	[13]
Glioma	DIS5RPEH	Strong	Altered Expression	[14]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[16]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Genetic Variation	[17]
Noonan syndrome 1	DIS7M92N	Strong	Biomarker	[18]
Noonan syndrome 3	DIS4MLJP	Strong	Genetic Variation	[19]
Prader-Willi syndrome	DISYWMLU	Strong	Biomarker	[10]
Prostate cancer	DISF190Y	Strong	Altered Expression	[20]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[21]
Robinow syndrome	DISK1CNU	Strong	Biomarker	[10]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[22]
Seckel syndrome	DISEVUBA	Strong	Biomarker	[10]
Silver-Russell syndrome	DISSVJ1D	Strong	Biomarker	[10]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Biomarker	[23]
Adult lymphoma	DISK8IZR	moderate	Biomarker	[24]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Biomarker	[25]
Chronic myelomonocytic leukaemia	DISDN5P7	moderate	Genetic Variation	[26]
Lymphoma	DISN6V4S	moderate	Biomarker	[24]
Melanoma	DIS1RRCY	moderate	Genetic Variation	[27]
Pediatric lymphoma	DIS51BK2	moderate	Biomarker	[24]
Ptosis	DISJZNIY	moderate	CausalMutation	[28]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[29]
Ventricular septal defect	DISICO41	moderate	CausalMutation	[28]
Hereditary gingival fibromatosis	DISN1ML3	Supportive	Autosomal dominant	[13]
Cardiofaciocutaneous syndrome	DISZJKSC	Disputed	Autosomal dominant	[1]
Costello syndrome	DISXVJH3	Disputed	Autosomal dominant	[1]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[30]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[30]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[31]
Epithelial ovarian cancer	DIS56MH2	Limited	Biomarker	[32]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[5]
Hermansky-Pudlak syndrome	DISCY0HQ	Limited	Biomarker	[33]
Lung adenocarcinoma	DISD51WR	Limited	Genetic Variation	[4]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[34]
Noonan syndrome with multiple lentigines	DIS014D0	Limited	Genetic Variation	[35]
Retinitis pigmentosa 3	DIS4VBK1	Limited	Genetic Variation	[36]

3 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 Son of sevenless homolog 1 (SOS1).	[37]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Son of sevenless homolog 1 (SOS1).	[55]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Son of sevenless homolog 1 (SOS1).	[55]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Son of sevenless homolog 1 (SOS1).	[38]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Son of sevenless homolog 1 (SOS1).	[39]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Son of sevenless homolog 1 (SOS1).	[40]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Son of sevenless homolog 1 (SOS1).	[41]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Son of sevenless homolog 1 (SOS1).	[42]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Son of sevenless homolog 1 (SOS1).	[43]
Marinol	DM70IK5	Approved	Marinol increases the expression of Son of sevenless homolog 1 (SOS1).	[44]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Son of sevenless homolog 1 (SOS1).	[45]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Son of sevenless homolog 1 (SOS1).	[46]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Son of sevenless homolog 1 (SOS1).	[43]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Son of sevenless homolog 1 (SOS1).	[47]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Son of sevenless homolog 1 (SOS1).	[48]
Dactinomycin	DM2YGNW	Approved	Dactinomycin decreases the expression of Son of sevenless homolog 1 (SOS1).	[49]
Dutasteride	DMQ4TJK	Approved	Dutasteride increases the expression of Son of sevenless homolog 1 (SOS1).	[50]
Tubocurarine	DMBZIVP	Approved	Tubocurarine decreases the expression of Son of sevenless homolog 1 (SOS1).	[47]
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of Son of sevenless homolog 1 (SOS1).	[51]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Son of sevenless homolog 1 (SOS1).	[45]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Son of sevenless homolog 1 (SOS1).	[52]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Son of sevenless homolog 1 (SOS1).	[53]
Tetrandrine	DMAOJBX	Phase 1	Tetrandrine decreases the expression of Son of sevenless homolog 1 (SOS1).	[54]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Son of sevenless homolog 1 (SOS1).	[56]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Son of sevenless homolog 1 (SOS1).	[57]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Son of sevenless homolog 1 (SOS1).	[58]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Son of sevenless homolog 1 (SOS1).	[59]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Son of sevenless homolog 1 (SOS1).	[60]
Chrysin	DM7V2LG	Investigative	Chrysin decreases the expression of Son of sevenless homolog 1 (SOS1).	[61]

References

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