Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTLJH8W)

• DOT Name: A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1)
• Synonyms: ADAM-TS 1; ADAM-TS1; ADAMTS-1; EC 3.4.24.-; METH-1
• Gene Name: ADAMTS1
• Related Disease: Autosomal dominant prognathism
• UniProt ID: ATS1_HUMAN
• PDB ID: 2JIH; 2V4B; 3Q2G; 3Q2H
• EC Number: 3.4.24.-
• Pfam ID: PF17771 ; PF19236 ; PF05986 ; PF01562 ; PF01421 ; PF19030 ; PF00090
• Sequence:
  MQRAVPEGFGRRKLGSDMGNAERAPGSRSFGPVPTLLLLAAALLAVSDALGRPSEEDEEL
  VVPELERAPGHGTTRLRLHAFDQQLDLELRPDSSFLAPGFTLQNVGRKSGSETPLPETDL
  AHCFYSGTVNGDPSSAAALSLCEGVRGAFYLLGEAYFIQPLPAASERLATAAPGEKPPAP
  LQFHLLRRNRQGDVGGTCGVVDDEPRPTGKAETEDEDEGTEGEDEGAQWSPQDPALQGVG
  QPTGTGSIRKKRFVSSHRYVETMLVADQSMAEFHGSGLKHYLLTLFSVAARLYKHPSIRN
  SVSLVVVKILVIHDEQKGPEVTSNAALTLRNFCNWQKQHNPPSDRDAEHYDTAILFTRQD
  LCGSQTCDTLGMADVGTVCDPSRSCSVIEDDGLQAAFTTAHELGHVFNMPHDDAKQCASL
  NGVNQDSHMMASMLSNLDHSQPWSPCSAYMITSFLDNGHGECLMDKPQNPIQLPGDLPGT
  SYDANRQCQFTFGEDSKHCPDAASTCSTLWCTGTSGGVLVCQTKHFPWADGTSCGEGKWC
  INGKCVNKTDRKHFDTPFHGSWGMWGPWGDCSRTCGGGVQYTMRECDNPVPKNGGKYCEG
  KRVRYRSCNLEDCPDNNGKTFREEQCEAHNEFSKASFGSGPAVEWIPKYAGVSPKDRCKL
  ICQAKGIGYFFVLQPKVVDGTPCSPDSTSVCVQGQCVKAGCDRIIDSKKKFDKCGVCGGN
  GSTCKKISGSVTSAKPGYHDIITIPTGATNIEVKQRNQRGSRNNGSFLAIKAADGTYILN
  GDYTLSTLEQDIMYKGVVLRYSGSSAALERIRSFSPLKEPLTIQVLTVGNALRPKIKYTY
  FVKKKKESFNAIPTFSAWVIEEWGECSKSCELGWQRRLVECRDINGQPASECAKEVKPAS
  TRPCADHPCPQWQLGEWSSCSKTCGKGYKKRSLKCLSHDGGVLSHESCDPLKKPKHFIDF
  CTMAECS
• Function: Cleaves aggrecan, a cartilage proteoglycan, at the '1938-Glu-|-Leu-1939' site (within the chondroitin sulfate attachment domain), and may be involved in its turnover. Has angiogenic inhibitor activity. Active metalloprotease, which may be associated with various inflammatory processes as well as development of cancer cachexia. May play a critical role in follicular rupture.
• Reactome Pathway:
  Defective B3GALTL causes PpS (R-HSA-5083635)
  O-glycosylation of TSR domain-containing proteins (R-HSA-5173214)
  Degradation of the extracellular matrix (R-HSA-1474228)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal dominant prognathism	DIS2G3FF	Limited	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) affects the response to substance of Topotecan.	[31]

28 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 A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[9]
Marinol	DM70IK5	Approved	Marinol decreases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[10]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[11]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[12]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[13]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[14]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[15]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[16]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[17]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[18]
Glucosamine	DM4ZLFD	Approved	Glucosamine decreases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[19]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[12]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[21]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[26]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[27]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[28]
Forskolin	DM6ITNG	Investigative	Forskolin decreases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[29]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[6]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).	[23]

References

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