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

General Information of Drug (ID: DM6KVIA)

• Drug Name: PF-3644022 Drug Info
• Synonyms: PF3644022; PF 3644022

Indication

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

• Cross-matching ID:
  PubChem CID: 44631903
  TTD Drug ID: DM6KVIA

Molecule-Related Drug Atlas

Drug(s) Targeting MAPK-activated protein kinase 2 (MAPKAPK2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zunsemetinib	DMNFNK7	Cryopyrin-associated periodic syndrome	4A60.1	Phase 2	[3]
CBP-501	DMCWVPU	Mesothelioma	2C51.2	Phase 1/2	[4]
MMI-0100	DMIMVEX	Airway inflammation	CA05	Phase 1	[5]
PMID19364658C33	DMSE1C3	Discovery agent	N.A.	Investigative	[6]
PMID17480064C16	DM4IABG	Discovery agent	N.A.	Investigative	[7]
CMPD1	DMKNUYF	Discovery agent	N.A.	Investigative	[8]

Drug(s) Affected By Mitogen-activated protein kinase 14 (MAPK14)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[9]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[10]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[11]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[12]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[13]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[14]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[15]
Ethacrynic acid	DM60QMR	Edema	MG29	Approved	[16]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[17]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[18]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
MAPK-activated protein kinase 2 (MAPKAPK2)	TTMUG9D	MAPK2_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Mitogen-activated protein kinase 14 (MAPK14)	OT5TCO3O	MK14_HUMAN	Gene/Protein Processing	[2]

References

• [1] A benzothiophene inhibitor of mitogen-activated protein kinase-activated protein kinase 2 inhibits tumor necrosis factor alpha production and has oral anti-inflammatory efficacy in acute and chronic models of inflammation. J Pharmacol Exp Ther. 2010 Jun;333(3):797-807.
• [2] Differential effect of p38 and MK2 kinase inhibitors on the inflammatory and toxicity biomarkers in vitro. Hum Exp Toxicol. 2018 May;37(5):521-531. doi: 10.1177/0960327117715901. Epub 2017 Jun 20.
• [3] Clinical pipeline report, company report or official report of Aclaris Therapeutics
• [4] National Cancer Institute Drug Dictionary (drug id 577812).
• [5] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2094).
• [6] Identification and SAR of squarate inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2). Bioorg Med Chem. 2009 May 1;17(9):3342-51.
• [7] Pyrrolopyridine inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2). J Med Chem. 2007 May 31;50(11):2647-54.
• [8] Synthesis and in vivo activity of MK2 and MK2 substrate-selective p38alpha(MAPK) inhibitors in Werner syndrome cells. Bioorg Med Chem Lett. 2007 Dec 15;17(24):6832-5.
• [9] Madecassoside ameliorates cisplatin-induced nephrotoxicity by inhibiting activation of the mitogen activated protein kinase pathway. Environ Toxicol. 2023 Jul;38(7):1473-1483. doi: 10.1002/tox.23777. Epub 2023 Apr 23.
• [10] Gingival Stromal Cells as an In Vitro Model: Cannabidiol Modulates Genes Linked With Amyotrophic Lateral Sclerosis. J Cell Biochem. 2017 Apr;118(4):819-828. doi: 10.1002/jcb.25757. Epub 2016 Nov 28.
• [11] Neuroprotective effects of glucomoringin-isothiocyanate against H(2)O(2)-Induced cytotoxicity in neuroblastoma (SH-SY5Y) cells. Neurotoxicology. 2019 Dec;75:89-104. doi: 10.1016/j.neuro.2019.09.008. Epub 2019 Sep 12.
• [12] Inflammation in methotrexate-induced pulmonary toxicity occurs via the p38 MAPK pathway. Toxicology. 2009 Feb 27;256(3):183-90. doi: 10.1016/j.tox.2008.11.016. Epub 2008 Nov 28.
• [13] Quercetin modulates Nrf2 and glutathione-related defenses in HepG2 cells: Involvement of p38. Chem Biol Interact. 2012 Jan 25;195(2):154-64.
• [14] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [15] Effects of chlorpromazine with and without UV irradiation on gene expression of HepG2 cells. Mutat Res. 2005 Aug 4;575(1-2):47-60. doi: 10.1016/j.mrfmmm.2005.03.002. Epub 2005 Apr 26.
• [16] Characterization of cell death induced by ethacrynic acid in a human colon cancer cell line DLD-1 and suppression by N-acetyl-L-cysteine. Cancer Sci. 2003 Oct;94(10):886-93.
• [17] Arsenic trioxide promotes ERK1/2-mediated phosphorylation and degradation of BIM(EL) to attenuate apoptosis in BEAS-2B cells. Chem Biol Interact. 2023 Jan 5;369:110304. doi: 10.1016/j.cbi.2022.110304. Epub 2022 Dec 10.
• [18] Aspirin-mediated COX-2 transcript stabilization via sustained p38 activation in human intestinal myofibroblasts. Mol Pharmacol. 2004 Feb;65(2):470-8.