Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2Z7VJH)

• DOT Name: Chitinase-3-like protein 1 (CHI3L1)
• Synonyms: 39 kDa synovial protein; Cartilage glycoprotein 39; CGP-39; GP-39; hCGP-39; YKL-40
• Gene Name: CHI3L1
• Related Disease:
  Lewy body dementia
  Lung cancer
  Lung carcinoma
  Amyloidosis
  Amyotrophic lateral sclerosis
  Arteriosclerosis
  Atherosclerosis
  Autoimmune disease
  B-cell neoplasm
  Breast neoplasm
  Cervical cancer
  Chronic obstructive pulmonary disease
  Colon cancer
  Coronary heart disease
  Epithelial ovarian cancer
  Frontotemporal dementia
  Gaucher disease
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Huntington disease
  Hyper-IgM syndrome type 1
  Inflammatory bowel disease
  Liver cirrhosis
  Melanoma
  Metastatic malignant neoplasm
  Mixed glioma
  Multiple sclerosis
  Nervous system disease
  Osteoarthritis
  Psoriasis
  Pulmonary disease
  Relapsing-remitting multiple sclerosis
  Sarcoidosis
  Systemic sclerosis
  Crohn disease
  Dementia
  Prostate cancer
  Prostate carcinoma
  Encephalitis
  Obstructive sleep apnea
  Advanced cancer
  Asthma
  Astrocytoma
  Coronary atherosclerosis
  Malignant glioma
  Pancreatic cancer
  Rectal carcinoma
  Stroke
  Type-1/2 diabetes
  Schizophrenia
• UniProt ID: CH3L1_HUMAN
• PDB ID: 1HJV; 1HJW; 1HJX; 1NWR; 1NWS; 1NWT; 1NWU; 7CJ2; 8DF1
• Pfam ID: PF00704
• Sequence:
  MGVKASQTGFVVLVLLQCCSAYKLVCYYTSWSQYREGDGSCFPDALDRFLCTHIIYSFAN
  ISNDHIDTWEWNDVTLYGMLNTLKNRNPNLKTLLSVGGWNFGSQRFSKIASNTQSRRTFI
  KSVPPFLRTHGFDGLDLAWLYPGRRDKQHFTTLIKEMKAEFIKEAQPGKKQLLLSAALSA
  GKVTIDSSYDIAKISQHLDFISIMTYDFHGAWRGTTGHHSPLFRGQEDASPDRFSNTDYA
  VGYMLRLGAPASKLVMGIPTFGRSFTLASSETGVGAPISGPGIPGRFTKEAGTLAYYEIC
  DFLRGATVHRILGQQVPYATKGNQWVGYDDQESVKSKVQYLKDRQLAGAMVWALDLDDFQ
  GSFCGQDLRFPLTNAIKDALAAT
• Function: Carbohydrate-binding lectin with a preference for chitin. Has no chitinase activity. May play a role in tissue remodeling and in the capacity of cells to respond to and cope with changes in their environment. Plays a role in T-helper cell type 2 (Th2) inflammatory response and IL-13-induced inflammation, regulating allergen sensitization, inflammatory cell apoptosis, dendritic cell accumulation and M2 macrophage differentiation. Facilitates invasion of pathogenic enteric bacteria into colonic mucosa and lymphoid organs. Mediates activation of AKT1 signaling pathway and subsequent IL8 production in colonic epithelial cells. Regulates antibacterial responses in lung by contributing to macrophage bacterial killing, controlling bacterial dissemination and augmenting host tolerance. Also regulates hyperoxia-induced injury, inflammation and epithelial apoptosis in lung.
• Tissue Specificity: Present in activated macrophages, articular chondrocytes, synovial cells as well as in liver. Very low or undetectable expression in non-inflammatory colon. Undetectable in muscle tissues, lung, pancreas, mononuclear cells, or fibroblasts.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lewy body dementia	DISAE66J	Definitive	Altered Expression	[1]
Lung cancer	DISCM4YA	Definitive	Biomarker	[2]
Lung carcinoma	DISTR26C	Definitive	Biomarker	[2]
Amyloidosis	DISHTAI2	Strong	Biomarker	[3]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Biomarker	[4]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[5]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[5]
Autoimmune disease	DISORMTM	Strong	Biomarker	[6]
B-cell neoplasm	DISVY326	Strong	Genetic Variation	[7]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[9]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Altered Expression	[10]
Colon cancer	DISVC52G	Strong	Altered Expression	[11]
Coronary heart disease	DIS5OIP1	Strong	Biomarker	[12]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[13]
Frontotemporal dementia	DISKYHXL	Strong	Biomarker	[14]
Gaucher disease	DISTW5JG	Strong	Altered Expression	[15]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[16]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[17]
Huntington disease	DISQPLA4	Strong	Biomarker	[18]
Hyper-IgM syndrome type 1	DISC91LV	Strong	Genetic Variation	[19]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[20]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[21]
Melanoma	DIS1RRCY	Strong	Altered Expression	[2]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[22]
Mixed glioma	DIS64UY3	Strong	Biomarker	[23]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[24]
Nervous system disease	DISJ7GGT	Strong	Biomarker	[25]
Osteoarthritis	DIS05URM	Strong	Biomarker	[26]
Psoriasis	DIS59VMN	Strong	Biomarker	[27]
Pulmonary disease	DIS6060I	Strong	Biomarker	[28]
Relapsing-remitting multiple sclerosis	DISSXFCF	Strong	Biomarker	[24]
Sarcoidosis	DISE5B8Z	Strong	Altered Expression	[29]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[30]
Crohn disease	DIS2C5Q8	moderate	Biomarker	[31]
Dementia	DISXL1WY	moderate	Altered Expression	[32]
Prostate cancer	DISF190Y	moderate	Biomarker	[33]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[33]
Encephalitis	DISLD1RL	Disputed	Biomarker	[34]
Obstructive sleep apnea	DIS0SVD1	Disputed	Biomarker	[35]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[36]
Asthma	DISW9QNS	Limited	Biomarker	[37]
Astrocytoma	DISL3V18	Limited	Altered Expression	[38]
Coronary atherosclerosis	DISKNDYU	Limited	Altered Expression	[39]
Malignant glioma	DISFXKOV	Limited	Biomarker	[40]
Pancreatic cancer	DISJC981	Limited	Biomarker	[41]
Rectal carcinoma	DIS8FRR7	Limited	Biomarker	[42]
Stroke	DISX6UHX	Limited	Biomarker	[43]
Type-1/2 diabetes	DISIUHAP	Limited	Genetic Variation	[44]
Schizophrenia	DISSRV2N	No Known	Unknown	[45]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Chitinase-3-like protein 1 (CHI3L1) decreases the response to substance of Etoposide.	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Chitinase-3-like protein 1 (CHI3L1).	[46]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Chitinase-3-like protein 1 (CHI3L1).	[63]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Chitinase-3-like protein 1 (CHI3L1).	[47]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Chitinase-3-like protein 1 (CHI3L1).	[48]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Chitinase-3-like protein 1 (CHI3L1).	[49]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Chitinase-3-like protein 1 (CHI3L1).	[50]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Chitinase-3-like protein 1 (CHI3L1).	[51]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Chitinase-3-like protein 1 (CHI3L1).	[52]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Chitinase-3-like protein 1 (CHI3L1).	[53]
Marinol	DM70IK5	Approved	Marinol increases the expression of Chitinase-3-like protein 1 (CHI3L1).	[54]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Chitinase-3-like protein 1 (CHI3L1).	[55]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Chitinase-3-like protein 1 (CHI3L1).	[56]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Chitinase-3-like protein 1 (CHI3L1).	[57]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Chitinase-3-like protein 1 (CHI3L1).	[58]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Chitinase-3-like protein 1 (CHI3L1).	[59]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Chitinase-3-like protein 1 (CHI3L1).	[60]
Glucosamine	DM4ZLFD	Approved	Glucosamine decreases the expression of Chitinase-3-like protein 1 (CHI3L1).	[61]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Chitinase-3-like protein 1 (CHI3L1).	[62]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Chitinase-3-like protein 1 (CHI3L1).	[64]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Chitinase-3-like protein 1 (CHI3L1).	[65]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Chitinase-3-like protein 1 (CHI3L1).	[66]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Chitinase-3-like protein 1 (CHI3L1).	[67]

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