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

General Information of Drug (ID: DM5H0R9)

• Drug Name: Enzastaurin Drug Info
• Synonyms: LY317615; LE-0014; LY317615, Enzastaurin; 3-(1-methyl-1H-indol-3-yl)-4-{1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]-1H-indol-3-yl}-1H-pyrrole-2,5-dione; 3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione

Indication

Disease Entry	ICD 11	Status	REF
Diffuse large B-cell lymphoma	2A81	Phase 3	[1]
Non-hodgkin lymphoma	2B33.5	Phase 3	[2]
Glioblastoma multiforme	2A00.0	Phase 2	[2]
Central nervous system disease	8A04-8D87	Phase 1	[2]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 176167
  ChEBI ID: CHEBI:91368
  CAS Number: CAS 170364-57-5
  TTD Drug ID: DM5H0R9
  INTEDE Drug ID: DR1898

Molecule-Related Drug Atlas

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RUBOXISTAURIN HYDROCHLORIDE	DMQOCD8	Lymphoma	2A80-2A86	Phase 3	[5]
Sotrastaurin acetate	DME53YS	Renal transplantation	NE84	Phase 2	[6]
LY333531	DMGMC8H	Solid tumour/cancer	2A00-2F9Z	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 RAC-alpha serine/threonine-protein kinase (AKT1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Capivasertib	DM9SKW8	Breast cancer	2C60-2C65	Approved	[1]
GDC-0068	DMWBZJD	Breast cancer	2C60-2C65	Phase 3	[1]
CI-1033	DMSI8N3	Lymphoma	2A80-2A86	Phase 2	[15]
CMX-2043	DMPSCVY	Cardiac disease	BA00-BE2Z	Phase 2	[16]
ARQ 092	DM5WK0J	Proteus syndrome	LD2C	Phase 2	[17]
GSK2110183	DMZHB37	leukaemia	2A60-2B33	Phase 2	[18]
RX-0201	DMTBAV3	Pancreatic cancer	2C10	Phase 2	[19]
PTX-200	DM0ZIT2	Breast cancer	2C60-2C65	Phase 2	[1]
Triciribine prodrug	DMBN1XS	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[18]
M2698	DM3PVBJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]

Drug(s) Targeting PI3-kinase gamma (PIK3CG)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BAY 80-6946	DMLOS5R	Follicular lymphoma	2A80	Approved	[20]
IPI-145	DMWA24P	Follicular lymphoma	2A80	Approved	[21]
Buparlisib	DM1WEHC	Breast cancer	2C60-2C65	Phase 3	[22]
Rigosertib	DMOSTXF	Myelodysplastic syndrome	2A37	Phase 3	[23]
GDC-0032	DMT4QHD	Breast cancer	2C60-2C65	Phase 3	[1]
PQR309	DMMCYZ8	Squamous head and neck cell carcinom	2D60.0	Phase 2	[24]
SAR245409	DMQM7IL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[25]
XL147	DMML7BE	Solid tumour/cancer	2A00-2F9Z	Phase 2	[25]
SF1126	DML10K3	Head and neck cancer	2D42	Phase 2	[26]
PF-05212384	DMBL3VD	Solid tumour/cancer	2A00-2F9Z	Phase 2	[27]

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	[28]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[29]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[30]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[31]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[32]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[33]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[34]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[35]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[29]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[36]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
PI3-kinase gamma (PIK3CG)	TTHBTOP	PK3CG_HUMAN	Inhibitor	[1]
Protein kinase C beta (PRKCB)	TTYPXQF	KPCB_HUMAN	Modulator	[3]
RAC-alpha serine/threonine-protein kinase (AKT1)	TTWTSCV	AKT1_HUMAN	Inhibitor	[1]

Drug-Metabolizing Enzyme (DME)

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

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] 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. (Ligand id: 5693).
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• [4] Phase I study of enzastaurin and bevacizumab in patients with advanced cancer: safety, efficacy and pharmacokinetics. Invest New Drugs. 2013 Jun;31(3):653-60.
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• [17] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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• [20] BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110 and p110 activities in tumor cell lines and xenograft models.Mol Cancer Ther.2013 Nov;12(11):2319-30.
• [21] PI3K-delta and PI3K-gamma inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol. 2013 Nov 21;20(11):1364-74.
• [22] Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
• [23] Phase I study of oral rigosertib (ON 01910.Na), a dual inhibitor of the PI3K and Plk1 pathways, in adult patients with advanced solid malignancies. Clin Cancer Res. 2014 Mar 15;20(6):1656-65.
• [24] 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: 2155).
• [25] 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: 2156).
• [26] An integrin-targeted, pan-isoform, phosphoinositide-3 kinase inhibitor, SF1126, has activity against multiple myeloma in vivo.Cancer Chemother Pharmacol.2013 Apr;71(4):867-81.
• [27] First-in-Human Study of PF-05212384 (PKI-587), a Small-Molecule, Intravenous, Dual Inhibitor of PI3K and mTOR in Patients with Advanced Cancer. Clin Cancer Res. 2015 Apr 15;21(8):1888-95.
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• [31] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [32] 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.
• [33] 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.
• [34] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [35] 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.
• [36] 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.