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

General Information of Drug (ID: DMZYGW0)

• Drug Name: SM-10661 Drug Info
• Synonyms: SM-12502; SM-10661 (racemate); Rac-cis-3,5-Dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride; (+)-cis-(2R,5S)-3,5-Dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride

Indication

Disease Entry	ICD 11	Status	REF
Sepsis	1G40-1G41	Discontinued in Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 178014
  CAS Number: CAS 158511-47-8
  TTD Drug ID: DMZYGW0

Molecule-Related Drug Atlas

Drug(s) Targeting Platelet-activating factor receptor (PTAFR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ticlopidine	DMO946V	Acute coronary syndrome	BA41	Approved	[4]
RUPATADINE	DMBPN7T	N. A.	N. A.	Phase 4	[5]
ISRAPAFANT	DMP61YB	Asthma	CA23	Phase 3	[6]
CMI-392	DM1NCUY	Psoriasis vulgaris	EA90	Phase 2	[7]
Lexipafant	DMZ2YBE	Nerve injury	ND56.4	Phase 2	[8]
YM-264	DMAZNVX	Sepsis	1G40-1G41	Phase 2	[9]
Dersalazine	DMH96JW	Inflammatory bowel disease	DD72	Phase 2	[10]
60P002	DMHBN8X	Dengue	1D20-1D2Z	Phase 2	[11]
PegCNTF	DMW7VGZ	Obesity	5B81	Phase 1	[12]
FOROPAFANT	DML1DGP	Asthma	CA23	Discontinued in Phase 3	[13]

Drug(s) Affected By Cytochrome P450 2A6 (CYP2A6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tegafur	DM31ZQM	Solid tumour/cancer	2A00-2F9Z	Approved	[14]
Methoxsalen	DME8FZ9	Cutaneous T-cell lymphoma	2B01	Approved	[15]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[16]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[17]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[19]
Ifosfamide	DMCT3I8	Adult central nervous system germ cell tumor		Approved	[20]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[21]
Letrozole	DMH07Y3	Estrogen-receptor positive breast cancer		Approved	[22]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[23]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Platelet-activating factor receptor (PTAFR)	TTQL5VC	PTAFR_HUMAN	Antagonist	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 2A6 (CYP2A6)	OT52TWG3	CP2A6_HUMAN	Regulation of Drug Effects	[3]

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004382)
• [2] Effect of the PAF-receptor antagonist SM-12502 on human platelets. Inflammation. 1996 Feb;20(1):71-85.
• [3] Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes. Arch Biochem Biophys. 2003 Jan 1;409(1):32-44.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Designed multiple ligands. An emerging drug discovery paradigm. J Med Chem. 2005 Oct 20;48(21):6523-43.
• [6] Amino acid residues critical for endoplasmic reticulum export and trafficking of platelet-activating factor receptor. J Biol Chem. 2010 Feb 19;285(8):5931-40.
• [7] Anti-inflammatory activities of LDP-392, a dual PAF receptor antagonist and 5-lipoxygenase inhibitor. Pharmacol Res. 2001 Sep;44(3):213-20.
• [8] Lexipafant and acute pancreatitis: a critical appraisal of the clinical trials.Eur J Surg.2002;168(4):215-9.
• [9] Effects of YM264, a novel PAF antagonist, on puromycin aminonucleoside-induced nephropathy in the rat. Biochem Biophys Res Commun. 1991 Apr 30;176(2):781-5.
• [10] The intestinal anti-inflammatory effect of dersalazine sodium is related to a down-regulation in IL-17 production in experimental models of rodent colitis. Br J Pharmacol. 2012 February; 165(3): 729-740.
• [11] Clinical pipeline report, company report or official report of 60 Degrees Pharmaceuticals.
• [12] Sch 37370: a new drug combining antagonism of platelet-activating factor (PAF) with antagonism of histamine. Agents Actions Suppl. 1991;34:313-21.
• [13] Biochemical and pharmacological activities of SR 27417, a highly potent, long-acting platelet-activating factor receptor antagonist. J Pharmacol Exp Ther. 1991 Oct;259(1):44-51.
• [14] Cyp2a6 is a principal enzyme involved in hydroxylation of 1,7-dimethylxanthine, a main caffeine metabolite, in humans. Drug Metab Dispos. 2005 Sep;33(9):1361-6. doi: 10.1124/dmd.105.004796. Epub 2005 Jun 24.
• [15] Mimicking gene defects to treat drug dependence. Ann N Y Acad Sci. 2000;909:233-46. doi: 10.1111/j.1749-6632.2000.tb06685.x.
• [16] Expression of CYP2A6 in tumor cells augments cellular sensitivity to tegafur. Jpn J Cancer Res. 2001 May;92(5):524-8. doi: 10.1111/j.1349-7006.2001.tb01125.x.
• [17] CYP1A1/1B1 and CYP2A6/2A13 activity is conserved in cultures of differentiated primary human tracheobronchial epithelial cells. Toxicol In Vitro. 2011 Jun;25(4):922-9.
• [18] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [19] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [20] Measurement of 4-hydroxylation of ifosfamide in human liver microsomes using the estimation of free and protein-bound acrolein and codetermination of keto- and carboxyifosfamide. J Cancer Res Clin Oncol. 2002 Jul;128(7):385-92.
• [21] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [22] Deactivation of anti-cancer drug letrozole to a carbinol metabolite by polymorphic cytochrome P450 2A6 in human liver microsomes. Xenobiotica. 2009 Nov;39(11):795-802. doi: 10.3109/00498250903171395.
• [23] A novel single nucleotide polymorphism altering stability and activity of CYP2a6. Biochem Biophys Res Commun. 2001 Mar 2;281(3):810-4. doi: 10.1006/bbrc.2001.4422.