Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY8BZIE)

• DOT Name: Collagenase 3 (MMP13)
• Synonyms: EC 3.4.24.-; Matrix metalloproteinase-13; MMP-13
• Gene Name: MMP13
• Related Disease:
  Spondyloepimetaphyseal dysplasia, Missouri type
  Metaphyseal chondrodysplasia, Spahr type
  Metaphyseal anadysplasia
• UniProt ID: MMP13_HUMAN
• PDB ID: 1EUB ; 1FLS ; 1FM1 ; 1PEX ; 1XUC ; 1XUD ; 1XUR ; 1YOU ; 1ZTQ ; 2D1N ; 2E2D ; 2OW9 ; 2OZR ; 2PJT ; 2YIG ; 3ELM ; 3I7G ; 3I7I ; 3KEC ; 3KEJ ; 3KEK ; 3KRY ; 3LJZ ; 3O2X ; 3TVC ; 3WV1 ; 3WV2 ; 3WV3 ; 3ZXH ; 456C ; 4A7B ; 4FU4 ; 4FVL ; 4G0D ; 4JP4 ; 4JPA ; 4L19 ; 5B5O ; 5B5P ; 5BOT ; 5BOY ; 5BPA ; 5UWK ; 5UWL ; 5UWM ; 5UWN ; 7JU8 ; 830C
• EC Number: 3.4.24.-
• Pfam ID: PF00045 ; PF00413 ; PF01471
• Sequence:
  MHPGVLAAFLFLSWTHCRALPLPSGGDEDDLSEEDLQFAERYLRSYYHPTNLAGILKENA
  ASSMTERLREMQSFFGLEVTGKLDDNTLDVMKKPRCGVPDVGEYNVFPRTLKWSKMNLTY
  RIVNYTPDMTHSEVEKAFKKAFKVWSDVTPLNFTRLHDGIADIMISFGIKEHGDFYPFDG
  PSGLLAHAFPPGPNYGGDAHFDDDETWTSSSKGYNLFLVAAHEFGHSLGLDHSKDPGALM
  FPIYTYTGKSHFMLPDDDVQGIQSLYGPGDEDPNPKHPKTPDKCDPSLSLDAITSLRGET
  MIFKDRFFWRLHPQQVDAELFLTKSFWPELPNRIDAAYEHPSHDLIFIFRGRKFWALNGY
  DILEGYPKKISELGLPKEVKKISAAVHFEDTGKTLLFSGNQVWRYDDTNHIMDKDYPRLI
  EEDFPGIGDKVDAVYEKNGYIYFFNGPIQFEYSIWSNRIVRVMPANSILWC
• Function: Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III collagen, but has the highest activity with soluble type II collagen. Can also degrade collagen type IV, type XIV and type X. May also function by activating or degrading key regulatory proteins, such as TGFB1 and CCN2. Plays a role in wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization and ossification. Required for normal embryonic bone development and ossification. Plays a role in the healing of bone fractures via endochondral ossification. Plays a role in wound healing, probably by a mechanism that involves proteolytic activation of TGFB1 and degradation of CCN2. Plays a role in keratinocyte migration during wound healing. May play a role in cell migration and in tumor cell invasion.
• Tissue Specificity: Detected in fetal cartilage and calvaria, in chondrocytes of hypertrophic cartilage in vertebrae and in the dorsal end of ribs undergoing ossification, as well as in osteoblasts and periosteal cells below the inner periosteal region of ossified ribs. Detected in chondrocytes from in joint cartilage that have been treated with TNF and IL1B, but not in untreated chondrocytes. Detected in T lymphocytes. Detected in breast carcinoma tissue.
• KEGG Pathway:
  IL-17 sig.ling pathway (hsa04657)
  Relaxin sig.ling pathway (hsa04926)
  Parathyroid hormone synthesis, secretion and action (hsa04928)
• Reactome Pathway:
  Degradation of the extracellular matrix (R-HSA-1474228)
  Activation of Matrix Metalloproteinases (R-HSA-1592389)
  Assembly of collagen fibrils and other multimeric structures (R-HSA-2022090)
  RUNX2 regulates genes involved in cell migration (R-HSA-8941332)
  Collagen degradation (R-HSA-1442490)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Spondyloepimetaphyseal dysplasia, Missouri type	DISUTWXH	Definitive	Autosomal dominant	[1]
Metaphyseal chondrodysplasia, Spahr type	DISZ16X4	Strong	Autosomal recessive	[2]
Metaphyseal anadysplasia	DISQCPVO	Supportive	Autosomal dominant	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Collagenase 3 (MMP13).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Collagenase 3 (MMP13).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Collagenase 3 (MMP13).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Collagenase 3 (MMP13).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Collagenase 3 (MMP13).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Collagenase 3 (MMP13).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Collagenase 3 (MMP13).	[10]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Collagenase 3 (MMP13).	[11]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Collagenase 3 (MMP13).	[12]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Collagenase 3 (MMP13).	[13]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Collagenase 3 (MMP13).	[14]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Collagenase 3 (MMP13).	[15]
Glucosamine	DM4ZLFD	Approved	Glucosamine affects the expression of Collagenase 3 (MMP13).	[16]
Sevoflurane	DMC9O43	Approved	Sevoflurane increases the expression of Collagenase 3 (MMP13).	[17]
2-deoxyglucose	DMIAHVU	Approved	2-deoxyglucose decreases the expression of Collagenase 3 (MMP13).	[18]
Ciprofloxacin XR	DM2NLS9	Approved	Ciprofloxacin XR decreases the expression of Collagenase 3 (MMP13).	[20]
Tetracycline	DMZA017	Approved	Tetracycline decreases the activity of Collagenase 3 (MMP13).	[21]
Chloramphenicol	DMFXEWT	Approved	Chloramphenicol increases the expression of Collagenase 3 (MMP13).	[22]
Ofloxacin	DM0VQN3	Approved	Ofloxacin decreases the expression of Collagenase 3 (MMP13).	[20]
Doxycycline	DM7ICNU	Approved	Doxycycline increases the expression of Collagenase 3 (MMP13).	[22]
Norfloxacin	DMIZ6W2	Approved	Norfloxacin decreases the expression of Collagenase 3 (MMP13).	[20]
Clindamycin	DM15HL8	Approved	Clindamycin increases the expression of Collagenase 3 (MMP13).	[22]
Prinomastat	DM9HOKG	Approved	Prinomastat decreases the activity of Collagenase 3 (MMP13).	[21]
Nalidixic acid	DMRM0JV	Approved	Nalidixic acid decreases the expression of Collagenase 3 (MMP13).	[20]
Berberine	DMC5Q8X	Phase 4	Berberine increases the expression of Collagenase 3 (MMP13).	[23]
Isoflavone	DM7U58J	Phase 4	Isoflavone decreases the expression of Collagenase 3 (MMP13).	[24]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Collagenase 3 (MMP13).	[9]
Chloroquine	DMSI5CB	Phase 3 Trial	Chloroquine increases the expression of Collagenase 3 (MMP13).	[26]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Collagenase 3 (MMP13).	[27]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Collagenase 3 (MMP13).	[29]
Scriptaid	DM9JZ21	Preclinical	Scriptaid affects the expression of Collagenase 3 (MMP13).	[30]
CP-471358	DMDEPKM	Terminated	CP-471358 decreases the activity of Collagenase 3 (MMP13).	[31]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Collagenase 3 (MMP13).	[32]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Collagenase 3 (MMP13).	[33]
Bilirubin	DMI0V4O	Investigative	Bilirubin increases the expression of Collagenase 3 (MMP13).	[34]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of Collagenase 3 (MMP13).	[36]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid increases the expression of Collagenase 3 (MMP13).	[11]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide increases the expression of Collagenase 3 (MMP13).	[37]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR increases the expression of Collagenase 3 (MMP13).	[38]
DIECKOL	DMBCK4G	Investigative	DIECKOL decreases the expression of Collagenase 3 (MMP13).	[39]
PAF	DMRZAQW	Investigative	PAF increases the expression of Collagenase 3 (MMP13).	[40]

3 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Dihydroxyacetone	DMM1LG2	Approved	Dihydroxyacetone decreases the secretion of Collagenase 3 (MMP13).	[19]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the secretion of Collagenase 3 (MMP13).	[25]
acrolein	DMAMCSR	Investigative	acrolein affects the secretion of Collagenase 3 (MMP13).	[35]

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 Collagenase 3 (MMP13).	[28]

References

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