Details of Drug Off-Target (DOT)

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

• DOT Name: Rho GTPase-activating protein 24 (ARHGAP24)
• Synonyms: Filamin-A-associated RhoGAP; FilGAP; RAC1- and CDC42-specific GTPase-activating protein of 72 kDa; RC-GAP72; Rho-type GTPase-activating protein 24; RhoGAP of 73 kDa; Sarcoma antigen NY-SAR-88; p73RhoGAP
• Gene Name: ARHGAP24
• Related Disease:
  Carcinoma
  T-cell lymphoma
  Acute lymphocytic leukaemia
  Adenocarcinoma
  Adenoma
  Adult glioblastoma
  Adult lymphoma
  Bladder cancer
  Bone osteosarcoma
  Burkitt lymphoma
  Cervical carcinoma
  Classic Hodgkin lymphoma
  Clear cell renal carcinoma
  Colon cancer
  Colorectal carcinoma
  Esophageal cancer
  Glioma
  Head-neck squamous cell carcinoma
  Medulloblastoma
  Metastatic malignant neoplasm
  Myelodysplastic syndrome
  Nephrotic syndrome, type 2
  Non-small-cell lung cancer
  Osteosarcoma
  Pediatric lymphoma
  Plasma cell myeloma
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Small lymphocytic lymphoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Wilms tumor
  Childhood acute lymphoblastic leukemia
  Cholangiocarcinoma
  Triple negative breast cancer
  Familial idiopathic steroid-resistant nephrotic syndrome
  Acute myelogenous leukaemia
  Asthma
  B-cell neoplasm
  Carcinoma of esophagus
  Cervical cancer
  Focal segmental glomerulosclerosis
  Hepatitis C virus infection
  Neoplasm of esophagus
  Non-hodgkin lymphoma
  Pancreatic cancer
• UniProt ID: RHG24_HUMAN
• Pfam ID: PF00169 ; PF00620
• Sequence:
  MEENNDSTENPQQGQGRQNAIKCGWLRKQGGFVKTWHTRWFVLKGDQLYYFKDEDETKPL
  GTIFLPGNKVSEHPCNEENPGKFLFEVVPGGDRDRMTANHESYLLMASTQNDMEDWVKSI
  RRVIWGPFGGGIFGQKLEDTVRYEKRYGNRLAPMLVEQCVDFIRQRGLKEEGLFRLPGQA
  NLVKELQDAFDCGEKPSFDSNTDVHTVASLLKLYLRELPEPVIPYAKYEDFLSCAKLLSK
  EEEAGVKELAKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSVQNLATVFGPNILRPK
  VEDPLTIMEGTVVVQQLMSVMISKHDCLFPKDAELQSKPQDGVSNNNEIQKKATMGQLQN
  KENNNTKDSPSRQCSWDKSESPQRSSMNNGSPTALSGSKTNSPKNSVHKLDVSRSPPLMV
  KKNPAFNKGSGIVTNGSFSSSNAEGLEKTQTTPNGSLQARRSSSLKVSGTKMGTHSVQNG
  TVRMGILNSDTLGNPTNVRNMSWLPNGYVTLRDNKQKEQAGELGQHNRLSTYDNVHQQFS
  MMNLDDKQSIDSATWSTSSCEISLPENSNSCRSSTTTCPEQDFFGGNFEDPVLDGPPQDD
  LSHPRDYESKSDHRSVGGRSSRATSSSDNSETFVGNSSSNHSALHSLVSSLKQEMTKQKI
  EYESRIKSLEQRNLTLETEMMSLHDELDQERKKFTMIEIKMRNAERAKEDAEKRNDMLQK
  EMEQFFSTFGELTVEPRRTERGNTIWIQ
• Function: Rho GTPase-activating protein involved in cell polarity, cell morphology and cytoskeletal organization. Acts as a GTPase activator for the Rac-type GTPase by converting it to an inactive GDP-bound state. Controls actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity. Able to suppress RAC1 and CDC42 activity in vitro. Overexpression induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. Isoform 2 is a vascular cell-specific GAP involved in modulation of angiogenesis.
• Tissue Specificity: Isoform 1 is widely expressed with a higher level in kidney. Isoform 2 is mainly expressed in endothelial cells.
• Reactome Pathway:
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RHOA GTPase cycle (R-HSA-8980692)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Definitive	Biomarker	[1]
T-cell lymphoma	DISSXRTQ	Definitive	Genetic Variation	[2]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[3]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[4]
Adenoma	DIS78ZEV	Strong	Genetic Variation	[5]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[6]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[7]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[1]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[8]
Burkitt lymphoma	DIS9D5XU	Strong	Biomarker	[9]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[10]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Genetic Variation	[11]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[12]
Colon cancer	DISVC52G	Strong	Biomarker	[13]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[14]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[15]
Glioma	DIS5RPEH	Strong	Altered Expression	[16]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[17]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[18]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[19]
Myelodysplastic syndrome	DISYHNUI	Strong	Posttranslational Modification	[20]
Nephrotic syndrome, type 2	DISIRFO1	Strong	GermlineCausalMutation	[21]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[22]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[8]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[7]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[23]
Prostate cancer	DISF190Y	Strong	Biomarker	[24]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[24]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[12]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[25]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[1]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[1]
Wilms tumor	DISB6T16	Strong	Altered Expression	[26]
Childhood acute lymphoblastic leukemia	DISJ5D6U	moderate	Genetic Variation	[27]
Cholangiocarcinoma	DIS71F6X	moderate	Genetic Variation	[28]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[29]
Familial idiopathic steroid-resistant nephrotic syndrome	DISQ53RS	Supportive	Autosomal dominant	[21]
Acute myelogenous leukaemia	DISCSPTN	Disputed	Altered Expression	[11]
Asthma	DISW9QNS	Limited	Genetic Variation	[30]
B-cell neoplasm	DISVY326	Limited	Biomarker	[31]
Carcinoma of esophagus	DISS6G4D	Limited	Biomarker	[15]
Cervical cancer	DISFSHPF	Limited	Biomarker	[10]
Focal segmental glomerulosclerosis	DISJNHH0	Limited	Biomarker	[21]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[32]
Neoplasm of esophagus	DISOLKAQ	Limited	Biomarker	[15]
Non-hodgkin lymphoma	DISS2Y8A	Limited	Biomarker	[33]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Rho GTPase-activating protein 24 (ARHGAP24).	[35]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Rho GTPase-activating protein 24 (ARHGAP24).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Rho GTPase-activating protein 24 (ARHGAP24).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Rho GTPase-activating protein 24 (ARHGAP24).	[38]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Rho GTPase-activating protein 24 (ARHGAP24).	[39]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Rho GTPase-activating protein 24 (ARHGAP24).	[40]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Rho GTPase-activating protein 24 (ARHGAP24).	[41]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Rho GTPase-activating protein 24 (ARHGAP24).	[42]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Rho GTPase-activating protein 24 (ARHGAP24).	[43]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Rho GTPase-activating protein 24 (ARHGAP24).	[44]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Rho GTPase-activating protein 24 (ARHGAP24).	[45]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Rho GTPase-activating protein 24 (ARHGAP24).	[47]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Rho GTPase-activating protein 24 (ARHGAP24).	[48]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Rho GTPase-activating protein 24 (ARHGAP24).	[49]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Rho GTPase-activating protein 24 (ARHGAP24).	[50]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Rho GTPase-activating protein 24 (ARHGAP24).	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Rho GTPase-activating protein 24 (ARHGAP24).	[46]

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