Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTGA1IV)

• DTT Name: Matrix metalloproteinase-8 (MMP-8)
• Synonyms: PMNL-CL; PMNL collagenase; Neutrophil collagenase; CLG1
• Gene Name: MMP8
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Peptidase
• UniProt ID: MMP8_HUMAN
• TTD ID: T08856
• EC Number: EC 3.4.24.34
• Sequence:
  MFSLKTLPFLLLLHVQISKAFPVSSKEKNTKTVQDYLEKFYQLPSNQYQSTRKNGTNVIV
  EKLKEMQRFFGLNVTGKPNEETLDMMKKPRCGVPDSGGFMLTPGNPKWERTNLTYRIRNY
  TPQLSEAEVERAIKDAFELWSVASPLIFTRISQGEADINIAFYQRDHGDNSPFDGPNGIL
  AHAFQPGQGIGGDAHFDAEETWTNTSANYNLFLVAAHEFGHSLGLAHSSDPGALMYPNYA
  FRETSNYSLPQDDIDGIQAIYGLSSNPIQPTGPSTPKPCDPSLTFDAITTLRGEILFFKD
  RYFWRRHPQLQRVEMNFISLFWPSLPTGIQAAYEDFDRDLIFLFKGNQYWALSGYDILQG
  YPKDISNYGFPSSVQAIDAAVFYRSKTYFFVNDQFWRYDNQRQFMEPGYPKSISGAFPGI
  ESKVDAVFQQEHFFHVFSGPRYYAFDLIAQRVTRVARGNKWLNCRYG
• Function: Can degrade fibrillar type I, II, and III collagens.
• Reactome Pathway:
  Degradation of the extracellular matrix (R-HSA-1474228)
  Activation of Matrix Metalloproteinases (R-HSA-1592389)
  Collagen degradation (R-HSA-1442490)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CIPEMASTAT	DM803GL	Rheumatoid arthritis	FA20	Phase 3	[1]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GM6001	DM7V9CT	Corneal ulcer	9A76	Discontinued in Phase 2	[2]
BB-1101	DM7GH5Z	Multiple sclerosis	8A40	Terminated	[3]
SC-44463	DMBPNKT	N. A.	N. A.	Terminated	[4]

19 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1-Hydroxyamine-2-Isobutylmalonic Acid	DM6FLXW	Discovery agent	N.A.	Investigative	[5]
2-(biphenyl-4-ylsulfonamido)pentanedioic acid	DMH3YBR	Discovery agent	N.A.	Investigative	[6]
2-(Biphenyl-4-ylsulfonyl)N-hydroxybenzamide	DMCNV5J	Discovery agent	N.A.	Investigative	[7]
2-HYDROXYCARBAMOYL-4-METHYL-PENTANOIC ACID	DMOT6V7	Discovery agent	N.A.	Investigative	[8]
2-Thiomethyl-3-Phenylpropanoic Acid	DMCEK6N	Discovery agent	N.A.	Investigative	[5]
3-(4-Methoxy-benzenesulfonyl)-cyclohexanethiol	DM206M1	Discovery agent	N.A.	Investigative	[9]
3-(4-Methoxy-benzenesulfonyl)-propane-1-thiol	DM7B1VT	Discovery agent	N.A.	Investigative	[9]
3-(4-Phenoxy-benzenesulfonyl)-cyclohexanethiol	DMBKDZ3	Discovery agent	N.A.	Investigative	[9]
3-(4-Phenoxy-benzenesulfonyl)-propane-1-thiol	DM2HBGL	Discovery agent	N.A.	Investigative	[9]
3-AMINO-AZACYCLOTRIDECAN-2-ONE	DM5073T	Discovery agent	N.A.	Investigative	[8]
4-amino-3-(4-(hexyloxy)phenyl)-4-oxobutanoic acid	DMGI0YV	Discovery agent	N.A.	Investigative	[6]
Glycinamid	DMTCEFV	Discovery agent	N.A.	Investigative	[5]
IK-862	DMJA4UE	Discovery agent	N.A.	Investigative	[10]
METHYLAMINO-PHENYLALANYL-LEUCYL-HYDROXAMIC ACID	DM9JECY	Discovery agent	N.A.	Investigative	[8]
MMI270	DM38N2K	Discovery agent	N.A.	Investigative	[11]
N-Hydroxy-2-(4-phenoxy-benzenesulfonyl)benzamide	DM4VADN	Discovery agent	N.A.	Investigative	[7]
Ro-37-9790	DM83QMZ	Discovery agent	N.A.	Investigative	[12]
SL422	DM3I2US	Discovery agent	N.A.	Investigative	[13]
[2-(Biphenyl-4-sulfonyl)phenyl]acetic Acid	DM37C25	Discovery agent	N.A.	Investigative	[7]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Rheumatoid arthritis	FA20	Synovial tissue	1.73E-01	-0.01	-0.05
Prostate cancer	2C82	Prostate	2.04E-03	-0.34	-0.66
Sarcoma	2C82	Muscle tissue	7.87E-01	-0.09	-0.56
Lung cancer	2C82	Lung tissue	1.19E-01	0.07	0.14

References

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• [2] Hydroxamate inhibitors of human gelatinase B (92 kDa), Bioorg. Med. Chem. Lett. 5(4):349-352 (1995).
• [3] New alpha-substituted succinate-based hydroxamic acids as TNFalpha convertase inhibitors. J Med Chem. 1999 Nov 18;42(23):4890-908.
• [4] Design and synthesis of a series of (2R)-N(4)-hydroxy-2-(3-hydroxybenzyl)-N(1)- [(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide derivati... J Med Chem. 2001 Oct 11;44(21):3347-50.
• [5] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [6] Ranking the selectivity of PubChem screening hits by activity-based protein profiling: MMP13 as a case study. Bioorg Med Chem. 2009 Feb 1;17(3):1101-8.
• [7] Design, synthesis, biological evaluation, and NMR studies of a new series of arylsulfones as selective and potent matrix metalloproteinase-12 inhib... J Med Chem. 2009 Oct 22;52(20):6347-61.
• [8] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [9] Synthesis and identification of conformationally constrained selective MMP inhibitors. Bioorg Med Chem Lett. 1999 Jul 5;9(13):1757-60.
• [10] Discovery of gamma-lactam hydroxamic acids as selective inhibitors of tumor necrosis factor alpha converting enzyme: design, synthesis, and structu... J Med Chem. 2002 Nov 7;45(23):4954-7.
• [11] Design, synthesis, and biological evaluation of potent thiazine- and thiazepine-based matrix metalloproteinase inhibitors. J Med Chem. 1999 Nov 4;42(22):4547-62.
• [12] 11,21-Bisphenyl-19-norpregnane derivatives are selective antiglucocorticoids, Bioorg. Med. Chem. Lett. 7(17):2299-2302 (1997).
• [13] Design, synthesis, and structure-activity relationships of macrocyclic hydroxamic acids that inhibit tumor necrosis factor alpha release in vitro and in vivo. J Med Chem. 2001 Aug 2;44(16):2636-60.