Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMNDLAS)

• Drug Name: PKF-242-484 Drug Info
• Synonyms: TNF-484

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 9886977
  CAS Number: CAS 205807-59-6
  TTD Drug ID: DMNDLAS

Molecule-Related Drug Atlas

Drug(s) Targeting Tumor necrosis factor (TNF)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Thalidomide	DM70BU5	Adult T-cell leukemia/lymphoma		Approved	[4]
Nafamostat	DMU1XOD	Pancreatitis	DC31-DC34	Approved	[5]
Pentoxifylline	DMU3DNC	Alcoholic hepatitis	DB94.1	Approved	[6]
Lenalidomide	DM6Q7U4	Adult T-cell leukemia/lymphoma		Approved	[7]
Enbrel	DM7RNP3	Arthritis	FA20	Approved	[8]
Golimumab	DMHZV7X	Psoriatic arthritis	FA21	Approved	[9]
Certolizumab	DM5CL9Z	Rheumatoid arthritis	FA20	Approved	[10]
Etanercept	DMCV109	Arthritis	FA20	Approved	[11]
Adalimumab	DMQMV1B	Crohn disease	DD70	Approved	[12]
Infliximab	DMH7OIA	Crohn disease	DD70	Approved	[13]

Drug(s) Targeting Matrix metalloproteinase-13 (MMP-13)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[14]
Apratastat	DM8W4N9	Rheumatoid arthritis	FA20	Phase 2	[15]
PMID17935984C1	DMO1IHL	Pain	MG30-MG3Z	Clinical trial	[16]
PMID29130358-Compound-Figure18(14a)	DMHIBTZ	N. A.	N. A.	Patented	[17]
PMID29130358-Compound-Figure16(9b)	DMPAQLZ	N. A.	N. A.	Patented	[17]
PMID29130358-Compound-Figure16(9a)	DMKX5R8	N. A.	N. A.	Patented	[17]
PMID29130358-Compound-Figure18(14)	DM7WXJ9	N. A.	N. A.	Patented	[17]
PMID29130358-Compound-Figure16(9c)	DM0ZRI9	N. A.	N. A.	Patented	[17]
GM6001	DM7V9CT	Corneal ulcer	9A76	Discontinued in Phase 2	[18]
RS-130830	DMOTANY	Hepatitis C virus infection	1E51.1	Discontinued in Phase 2	[19]

Drug(s) Targeting Matrix metalloproteinase-1 (MMP-1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Prinomastat	DM9HOKG	Lung cancer	2C25.0	Approved	[20]
Marimastat	DM6V34C	Pancreatic cancer	2C10	Phase 3	[21]
CIPEMASTAT	DM803GL	Rheumatoid arthritis	FA20	Phase 3	[22]
Apratastat	DM8W4N9	Rheumatoid arthritis	FA20	Phase 2	[15]
PMID29130358-Compound-Figure18(14a)	DMHIBTZ	N. A.	N. A.	Patented	[17]
PMID29130358-Compound-Figure10(2a)	DMFWXPS	N. A.	N. A.	Patented	[17]
BMS 275291	DMKSFPE	Kaposi sarcoma	2B57	Discontinued in Phase 3	[23]
GM6001	DM7V9CT	Corneal ulcer	9A76	Discontinued in Phase 2	[24]
RS-130830	DMOTANY	Hepatitis C virus infection	1E51.1	Discontinued in Phase 2	[19]
XL784	DMICR39	Diabetic nephropathy	GB61.Z	Discontinued in Phase 2	[25]

Drug(s) Targeting TNF alpha converting enzyme (ADAM17)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Apratastat	DM8W4N9	Rheumatoid arthritis	FA20	Phase 2	[15]
Aderbasib	DMYOMSC	Breast cancer	2C60-2C65	Phase 1/2	[26]
GW-3333	DM3PMAZ	Chronic obstructive pulmonary disease	CA22	Preclinical	[27]
DPC-333	DM4JBQD	Inflammatory bowel disease	DD72	Terminated	[27]
IK-862	DMJA4UE	Discovery agent	N.A.	Investigative	[28]
SR-973	DMU48OD	Discovery agent	N.A.	Investigative	[29]
SL422	DM3I2US	Discovery agent	N.A.	Investigative	[30]
N-hydroxy-3-(2-oxo-2H-chromen-3-yl)propanamide	DMWXUCT	Discovery agent	N.A.	Investigative	[31]
N-hydroxy-3-(6-methoxy-2-oxo-2H-chromen-3-yl)	DMA6EPH	Discovery agent	N.A.	Investigative	[31]
PKF-241-466	DM04C9V	Discovery agent	N.A.	Investigative	[2]

Drug(s) Targeting Matrix metalloproteinase-3 (MMP-3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID29130358-Compound-Figure10(2a)	DMFWXPS	N. A.	N. A.	Patented	[17]
GM6001	DM7V9CT	Corneal ulcer	9A76	Discontinued in Phase 2	[24]
RS-130830	DMOTANY	Hepatitis C virus infection	1E51.1	Discontinued in Phase 2	[19]
PG-530742	DMELXBQ	Myocardial infarction	BA41-BA43	Discontinued in Phase 2	[32]
Batimastat	DM92VRP	Idiopathic pulmonary fibrosis	CB03.4	Preclinical	[33]
SC-44463	DMBPNKT	N. A.	N. A.	Terminated	[34]
BB-1101	DM7GH5Z	Multiple sclerosis	8A40	Terminated	[35]
L-696418	DMV785R	N. A.	N. A.	Terminated	[36]
RO-319790	DML3NEU	Rheumatoid arthritis	FA20	Terminated	[37]
MMI270	DM38N2K	Discovery agent	N.A.	Investigative	[38]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Matrix metalloproteinase-1 (MMP-1)	TTMX39J	MMP1_HUMAN	Inhibitor	[1]
Matrix metalloproteinase-13 (MMP-13)	TTHY57M	MMP13_HUMAN	Inhibitor	[1]
Matrix metalloproteinase-3 (MMP-3)	TTUZ2L5	MMP3_HUMAN	Inhibitor	[1]
TNF alpha converting enzyme (ADAM17)	TT6AZXG	ADA17_HUMAN	Inhibitor	[2]
Tumor necrosis factor (TNF)	TTF8CQI	TNFA_HUMAN	Inhibitor	[3]

References

• [1] A cassette-dosing approach for improvement of oral bioavailability of dual TACE/MMP inhibitors. Bioorg Med Chem Lett. 2006 May 15;16(10):2632-6.
• [2] Current perspective of TACE inhibitors: a review. Bioorg Med Chem. 2009 Jan 15;17(2):444-59.
• [3] Beta-aryl-succinic acid hydroxamates as dual inhibitors of matrix metalloproteinases and tumor necrosis factor alpha converting enzyme. J Med Chem. 2002 May 23;45(11):2289-93.
• [4] Efficacy of different thalidomide regimens for patients with multiple myeloma and its relationship with TNF-alpha level. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008 Dec;16(6):1312-5.
• [5] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [6] Targeted therapies in myelodysplastic syndromes: ASH 2003 review. Semin Hematol. 2004 Apr;41(2 Suppl 4):13-20.
• [7] Thalidomide and thalidomide analogues for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD007351.
• [8] Oral pentoxifylline inhibits release of tumor necrosis factor-alpha from human peripheral blood monocytes : a potential treatment for aseptic loose... J Bone Joint Surg Am. 2001 Jul;83(7):1057-61.
• [9] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [10] Emerging drugs for rheumatoid arthritis. Expert Opin Emerg Drugs. 2008 Mar;13(1):175-96.
• [11] The potential of biologics for the treatment of asthma. Nat Rev Drug Discov. 2012 Dec;11(12):958-72.
• [12] Adalimumab for psoriasis patients who are non-responders to etanercept: open-label prospective evaluation. J Eur Acad Dermatol Venereol. 2009 Dec;23(12):1394-7.
• [13] Drug insight: tumor necrosis factor-converting enzyme as a pharmaceutical target for rheumatoid arthritis. Nat Clin Pract Rheumatol. 2008 Jun;4(6):300-9.
• [14] High throughput screening of potentially selective MMP-13 exosite inhibitors utilizing a triple-helical FRET substrate. Bioorg Med Chem. 2009 Feb 1;17(3):990-1005.
• [15] Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates. Bioorg Med Chem Lett. 2006 Mar 15;16(6):1605-9.
• [16] Potent, selective spiropyrrolidine pyrimidinetrione inhibitors of MMP-13. Bioorg Med Chem Lett. 2007 Dec 1;17(23):6529-34.
• [17] Gelatinase inhibitors: a patent review (2011-2017).Expert Opin Ther Pat. 2018 Jan;28(1):31-46.
• [18] Discovery and characterization of a novel inhibitor of matrix metalloprotease-13 that reduces cartilage damage in vivo without joint fibroplasia si... J Biol Chem. 2007 Sep 21;282(38):27781-91.
• [19] Structure-based design of potent and selective inhibitors of collagenase-3 (MMP-13). Bioorg Med Chem Lett. 2005 Feb 15;15(4):1101-6.
• [20] AG-3340 (Agouron Pharmaceuticals Inc). IDrugs. 2000 Mar;3(3):336-45.
• [21] Metalloelastase (MMP-12) induced inflammatory response in mice airways: effects of dexamethasone, rolipram and marimastat. Eur J Pharmacol. 2007 Mar 15;559(1):75-81.
• [22] Matrix metalloproteinase inhibition lowers mortality and brain injury in experimental pneumococcal meningitis. Infect Immun. 2014 Apr;82(4):1710-8.
• [23] Phase 1/2 trial of BMS-275291 in patients with human immunodeficiency virus-related Kaposi sarcoma: a multicenter trial of the AIDS Malignancy Consortium. Cancer. 2008 Mar 1;112(5):1083-8.
• [24] Introduction of the 4-(4-bromophenyl)benzenesulfonyl group to hydrazide analogs of Ilomastat leads to potent gelatinase B (MMP-9) inhibitors with i... Bioorg Med Chem. 2008 Sep 15;16(18):8745-59.
• [25] Agents in development for the treatment of diabetic nephropathy. Expert Opin Emerg Drugs. 2008 Sep;13(3):447-63.
• [26] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [27] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
• [28] Specific targeting of metzincin family members with small-molecule inhibitors: progress toward a multifarious challenge. Bioorg Med Chem. 2008 Oct 1;16(19):8781-94.
• [29] Synthesis and evaluation of succinoyl-caprolactam gamma-secretase inhibitors. Bioorg Med Chem Lett. 2006 May 1;16(9):2357-63.
• [30] 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.
• [31] Chromen-based TNF-alpha converting enzyme (TACE) inhibitors: design, synthesis, and biological evaluation. Bioorg Med Chem. 2008 Jan 1;16(1):530-5.
• [32] Selective matrix metalloproteinase inhibition attenuates progression of left ventricular dysfunction and remodeling in dogs with chronic heart fail... Am J Physiol Heart Circ Physiol. 2006 Jun;290(6):H2522-7.
• [33] Matrix metalloproteinase inhibitor BB-94 (batimastat) inhibits human colon tumor growth and spread in a patient-like orthotopic model in nude mice. Cancer Res. 1994 Sep 1;54(17):4726-8.
• [34] Amide surrogates of matrix metalloproteinase inhibitors: Urea and sulfonamide mimics, Bioorg. Med. Chem. Lett. 7(18):2331-2336 (1997).
• [35] Broad spectrum matrix metalloproteinase inhibitors: an examination of succinamide hydroxamate inhibitors with P1 C alpha gem-disubstitution. Bioorg Med Chem Lett. 1998 Jun 16;8(12):1443-8.
• [36] Inhibition of matrix metalloproteinases by N-carboxyalkyl peptides containing extended alkyl residues At P1', Bioorg. Med. Chem. Lett. 5(6):539-542 (1995).
• [37] The asymmetric synthesis and in vitro characterization of succinyl mercaptoalcohol and mercaptoketone inhibitors of matrix metalloproteinases. Bioorg Med Chem Lett. 1998 May 19;8(10):1163-8.
• [38] Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nat Rev Cancer. 2002 Sep;2(9):657-72.