Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTM4X11)

• DOT Name: Keratin, type II cytoskeletal 8 (KRT8)
• Synonyms: Cytokeratin-8; CK-8; Keratin-8; K8; Type-II keratin Kb8
• Gene Name: KRT8
• Related Disease:
  Acute liver failure
  Adenocarcinoma
  Advanced cancer
  Breast neoplasm
  Chronic pancreatitis
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  High blood pressure
  Inflammatory bowel disease
  Liver cancer
  Lung adenocarcinoma
  Lung carcinoma
  Lung neoplasm
  Lung squamous cell carcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Non-small-cell lung cancer
  Ovarian neoplasm
  Ovarian serous adenocarcinoma
  Papillary renal cell carcinoma
  Prostate carcinoma
  Renal cell carcinoma
  Squamous cell carcinoma
  Carcinoma
  Cystic fibrosis
  Lung cancer
  Clear cell renal carcinoma
  Colitis
  Cirrhosis, familial
  Gastric cancer
  Precancerous condition
  Prostate cancer
• UniProt ID: K2C8_HUMAN
• PDB ID: 7K3C; 7K3X; 7K3Y
• Pfam ID: PF00038 ; PF16208
• Sequence:
  MSIRVTQKSYKVSTSGPRAFSSRSYTSGPGSRISSSSFSRVGSSNFRGGLGGGYGGASGM
  GGITAVTVNQSLLSPLVLEVDPNIQAVRTQEKEQIKTLNNKFASFIDKVRFLEQQNKMLE
  TKWSLLQQQKTARSNMDNMFESYINNLRRQLETLGQEKLKLEAELGNMQGLVEDFKNKYE
  DEINKRTEMENEFVLIKKDVDEAYMNKVELESRLEGLTDEINFLRQLYEEEIRELQSQIS
  DTSVVLSMDNSRSLDMDSIIAEVKAQYEDIANRSRAEAESMYQIKYEELQSLAGKHGDDL
  RRTKTEISEMNRNISRLQAEIEGLKGQRASLEAAIADAEQRGELAIKDANAKLSELEAAL
  QRAKQDMARQLREYQELMNVKLALDIEIATYRKLLEGEESRLESGMQNMSIHTKTTSGYA
  GGLSSAYGGLTSPGLSYSLGSSFGSGAGSSSFSRTSSSRAVVVKKIETRDGKLVSESSDV
  LPK
• Function: Together with KRT19, helps to link the contractile apparatus to dystrophin at the costameres of striated muscle.
• Tissue Specificity: Observed in muscle fibers accumulating in the costameres of myoplasm at the sarcolemma membrane in structures that contain dystrophin and spectrin. Expressed in gingival mucosa and hard palate of the oral cavity.
• Reactome Pathway:
  Formation of the cornified envelope (R-HSA-6809371)
  Keratinization (R-HSA-6805567)

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute liver failure	DIS5EZKX	Strong	Genetic Variation	[1]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Chronic pancreatitis	DISBUOMJ	Strong	Genetic Variation	[5]
Colon cancer	DISVC52G	Strong	Genetic Variation	[6]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[6]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[6]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[6]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[6]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[6]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[2]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[2]
High blood pressure	DISY2OHH	Strong	Biomarker	[8]
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[9]
Liver cancer	DISDE4BI	Strong	Biomarker	[10]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[11]
Lung carcinoma	DISTR26C	Strong	Posttranslational Modification	[12]
Lung neoplasm	DISVARNB	Strong	Biomarker	[13]
Lung squamous cell carcinoma	DISXPIBD	Strong	Altered Expression	[11]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	Strong	Altered Expression	[15]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[16]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[6]
Ovarian serous adenocarcinoma	DISSU72Z	Strong	Genetic Variation	[6]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[17]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[18]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[17]
Squamous cell carcinoma	DISQVIFL	Strong	Posttranslational Modification	[19]
Carcinoma	DISH9F1N	moderate	Posttranslational Modification	[19]
Cystic fibrosis	DIS2OK1Q	moderate	Genetic Variation	[20]
Lung cancer	DISCM4YA	moderate	Posttranslational Modification	[12]
Clear cell renal carcinoma	DISBXRFJ	Disputed	Biomarker	[21]
Colitis	DISAF7DD	Disputed	Biomarker	[22]
Cirrhosis, familial	DISGG52B	Limited	Unknown	[23]
Gastric cancer	DISXGOUK	Limited	Biomarker	[24]
Precancerous condition	DISV06FL	Limited	Biomarker	[25]
Prostate cancer	DISF190Y	Limited	Altered Expression	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	Keratin, type II cytoskeletal 8 (KRT8) affects the response to substance of DTI-015.	[67]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[26]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[27]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[28]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[29]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[30]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[31]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[32]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[33]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[34]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[35]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[36]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[37]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[38]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Keratin, type II cytoskeletal 8 (KRT8).	[39]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[40]
Selenium	DM25CGV	Approved	Selenium increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[41]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Keratin, type II cytoskeletal 8 (KRT8).	[42]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[43]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[45]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[46]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[47]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[48]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[49]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[28]
Beta-carotene	DM0RXBT	Approved	Beta-carotene decreases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[28]
Vitamin A	DMJ2AH4	Approved	Vitamin A increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[28]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[50]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[45]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[51]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[52]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[53]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[54]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[55]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[56]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[57]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[58]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[59]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[61]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[63]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[28]
Flavone	DMEQH6J	Investigative	Flavone increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[65]
SU 6656	DMF1P6W	Investigative	SU 6656 increases the expression of Keratin, type II cytoskeletal 8 (KRT8).	[66]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Menadione	DMSJDTY	Approved	Menadione increases the phosphorylation of Keratin, type II cytoskeletal 8 (KRT8).	[44]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the methylation of Keratin, type II cytoskeletal 8 (KRT8).	[60]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Keratin, type II cytoskeletal 8 (KRT8).	[62]

1 Drug(s) Affected the Biochemical Pathways of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
acrolein	DMAMCSR	Investigative	acrolein increases the metabolism of Keratin, type II cytoskeletal 8 (KRT8).	[64]

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