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

General Information of Drug (ID: DMGMC8H)

• Drug Name: LY333531 Drug Info
• Synonyms: Ruboxistaurin; 169939-94-0; LY-333531; Ruboxistaurin [INN]; LY 333531; UNII-721809WQCP; 721809WQCP; K00587a; 13-((Dimethylamino)methyl)-10,11,14,15-tetrahydro-4,9:16,21-dimetheno-1H,13H-dibenzo(e,k)pyrrolo(3,4-h)(1,4,13)oxadiazacyclohexadecene-1,3(2H)-dione; CHEMBL432130; (9S)-9-[(dimethylamino)methyl]-6,7,10,11-tetrahydro-9H,18H-5,21:12,17-di(metheno)dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecine-18,20(19H)-dione; Br-WR99210

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 153999
  CAS Number: CAS 169939-94-0
  TTD Drug ID: DMGMC8H
  INTEDE Drug ID: DR1860

Molecule-Related Drug Atlas

Drug(s) Targeting Protein kinase C beta (PRKCB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Enzastaurin	DM5H0R9	Diffuse large B-cell lymphoma	2A81	Phase 3	[5]
RUBOXISTAURIN HYDROCHLORIDE	DMQOCD8	Lymphoma	2A80-2A86	Phase 3	[6]
Sotrastaurin acetate	DME53YS	Renal transplantation	NE84	Phase 2	[7]
MS-553	DM7ER9J	Chronic lymphocytic leukaemia	2A82.0	Phase 1	[8]
Linetastine	DMF8B62	Rhinitis	FA20	Discontinued in Phase 2	[9]
BALANOL	DMDLN9E	N. A.	N. A.	Terminated	[10]
RO-320432	DMFZ1YW	N. A.	N. A.	Terminated	[11]
LY-317644	DMM20PI	N. A.	N. A.	Terminated	[12]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[13]
LY-326449	DMN53M4	Discovery agent	N.A.	Investigative	[14]

Drug(s) Targeting Polypeptide deformylase (PDF)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Proguanil	DMBL79I	Malaria	1F40-1F45	Approved	[15]
Meprobamate	DMHM93Y	Anxiety		Approved	[16]
Pralatrexate	DMAO80I	Breast cancer	2C60-2C65	Approved	[17]
Ustekinumab	DMHTYK3	Plaque psoriasis	EA90.0	Approved	[18]
Trimetrexate	DMDEA85	Toxoplasmosis	1F57	Approved	[19]
MCB-3837	DM0R4Z5	Malaria	1F40-1F45	Approved	[16]
Chlorproguanil	DM1IFGT	Malaria	1F40-1F45	Approved	[16]
Metoprine	DM5GQD7	Advanced cancer	2A00-2F9Z	Phase 2	[20]
Aminopterin	DMQ9RBV	leukaemia	2A60-2B33	Withdrawn from market	[21]
2-Sulfhydryl-Ethanol	DMJBO3D	Discovery agent	N.A.	Investigative	[22]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[23]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[24]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[25]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[26]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[27]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[28]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[29]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[30]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[24]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Polypeptide deformylase (PDF)	TT9SL3Q	DEFM_HUMAN	Inhibitor	[2]
Protein kinase C beta (PRKCB)	TTYPXQF	KPCB_HUMAN	Inhibitor	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[4]

References

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• [7] Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.
• [8] ClinicalTrials.gov (NCT03492125) A Study Of The Selective PKC-beta Inhibitor MS- 553. U.S. National Institutes of Health.
• [9] Potential new medical therapies for diabetic retinopathy: protein kinase C inhibitors. Am J Ophthalmol. 2002 May;133(5):693-8.
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• [15] Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10931-6.
• [16] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
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• [19] Expression and characterization of recombinant human-derived Pneumocystis carinii dihydrofolate reductase. Antimicrob Agents Chemother. 2000 Nov;44(11):3092-6.
• [20] Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 2006 Dec;58(6):826-34.
• [21] Loss of folylpoly-gamma-glutamate synthetase activity is a dominant mechanism of resistance to polyglutamylation-dependent novel antifolates in multiple human leukemia sublines. Int J Cancer. 2003 Feb 20;103(5):587-99.
• [22] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [23] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [24] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [25] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [26] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [27] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [28] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [29] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [30] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [31] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.