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

General Information of Drug (ID: DM1HMJ5)

• Drug Name: PROSTRATIN Drug Info

Indication

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 454217
  ChEBI ID: CHEBI:69818
  CAS Number: CAS 60857-08-1
  TTD Drug ID: DM1HMJ5

Molecule-Related Drug Atlas

Drug(s) Targeting Protein kinase C alpha (PRKCA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sodium phenylbutyrate	DMXLBCQ	Spinal muscular atrophy	8B61	Approved	[3]
Sotrastaurin acetate	DME53YS	Renal transplantation	NE84	Phase 2	[4]
PMID28460551-Compound-3	DMA1FRM	N. A.	N. A.	Patented	[5]
ISIS 3521	DMZFS69	N. A.	N. A.	Discontinued in Phase 2	[6]
BALANOL	DMDLN9E	N. A.	N. A.	Terminated	[7]
RO-320432	DMFZ1YW	N. A.	N. A.	Terminated	[8]
LY-317644	DMM20PI	N. A.	N. A.	Terminated	[9]
Acteoside	DM0YHKB	Nephritis	GB40	Terminated	[10]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[11]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[12]

Drug(s) Targeting PKC-eta messenger RNA (PRKCH mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BALANOL	DMDLN9E	N. A.	N. A.	Terminated	[7]
LY-326449	DMN53M4	Discovery agent	N.A.	Investigative	[13]
8-Octyl-benzolactam-V9	DM4Z15M	Discovery agent	N.A.	Investigative	[14]
ISIS 6445	DMXJ4SO	Discovery agent	N.A.	Investigative	[15]
ISIS 6432	DMQHN43	Discovery agent	N.A.	Investigative	[15]
ISIS 6553	DM5L387	Discovery agent	N.A.	Investigative	[15]
ISIS 6581	DMEAVPQ	Discovery agent	N.A.	Investigative	[15]
ISIS 6442	DM7KSRG	Discovery agent	N.A.	Investigative	[15]
ISIS 6434	DMNVLE2	Discovery agent	N.A.	Investigative	[15]
ISIS 6431	DMEUCI2	Discovery agent	N.A.	Investigative	[15]

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	[16]
RUBOXISTAURIN HYDROCHLORIDE	DMQOCD8	Lymphoma	2A80-2A86	Phase 3	[17]
Sotrastaurin acetate	DME53YS	Renal transplantation	NE84	Phase 2	[4]
LY333531	DMGMC8H	Solid tumour/cancer	2A00-2F9Z	Phase 2	[18]
MS-553	DM7ER9J	Chronic lymphocytic leukaemia	2A82.0	Phase 1	[19]
Linetastine	DMF8B62	Rhinitis	FA20	Discontinued in Phase 2	[20]
BALANOL	DMDLN9E	N. A.	N. A.	Terminated	[7]
RO-320432	DMFZ1YW	N. A.	N. A.	Terminated	[8]
LY-317644	DMM20PI	N. A.	N. A.	Terminated	[9]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[11]

Drug(s) Targeting Protein kinase C delta (PRKCD)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
KAI-9803	DMELJDI	Acute myocardial infarction	BA41	Phase 1/2	[21]
RO-320432	DMFZ1YW	N. A.	N. A.	Terminated	[8]
LY-317644	DMM20PI	N. A.	N. A.	Terminated	[9]
AD 198	DMJFY2I	N. A.	N. A.	Terminated	[22]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[11]
LY-326449	DMN53M4	Discovery agent	N.A.	Investigative	[13]
[2,2':5',2'']Terthiophen-4-yl-methanol	DMRQC1F	Discovery agent	N.A.	Investigative	[23]
4-[1-(4-hydroxyphenyl)-3-methyl-1-butenyl]phenol	DM8IYG1	Discovery agent	N.A.	Investigative	[24]
2-(4-Hydroxy-phenyl)-3,3-diphenyl-acrylonitrile	DMNGW1A	Discovery agent	N.A.	Investigative	[24]
[2,2':5',2'']Terthiophene-4,5''-dicarbaldehyde	DMWDNLI	Discovery agent	N.A.	Investigative	[23]

Drug(s) Targeting Protein kinase C gamma (PRKCG)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Midostaurin	DMI6E0R	Acute myeloid leukaemia	2A60	Approved	[25]
BALANOL	DMDLN9E	N. A.	N. A.	Terminated	[7]
RO-320432	DMFZ1YW	N. A.	N. A.	Terminated	[8]
LY-317644	DMM20PI	N. A.	N. A.	Terminated	[9]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[11]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[26]
3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione	DMDO175	Discovery agent	N.A.	Investigative	[27]
3,4-diphenyl-1H-pyrrole-2,5-dione	DMPK6YT	Discovery agent	N.A.	Investigative	[27]
3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione	DMGC7RY	Discovery agent	N.A.	Investigative	[27]
3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione	DM3EV9N	Discovery agent	N.A.	Investigative	[27]

Drug(s) Targeting PKC-delta messenger RNA (PRKCD mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BALANOL	DMDLN9E	N. A.	N. A.	Terminated	[7]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[26]
LY-326449	DMN53M4	Discovery agent	N.A.	Investigative	[13]
8-Octyl-benzolactam-V9	DM4Z15M	Discovery agent	N.A.	Investigative	[14]
Go 6983	DMKVTZN	Discovery agent	N.A.	Investigative	[28]
Diheptan-3-yl 5-(hydroxymethyl)isophthalate	DMBAY7P	Discovery agent	N.A.	Investigative	[29]
Dihexan-3-yl 5-(hydroxymethyl)isophthalate	DM8TBQ9	Discovery agent	N.A.	Investigative	[29]
ISIS 10310	DMT6H9S	Discovery agent	N.A.	Investigative	[15]
ISIS 17252	DMW40NK	Discovery agent	N.A.	Investigative	[30]
ISIS 10303	DM205TE	Discovery agent	N.A.	Investigative	[15]

Drug(s) Targeting PKC-theta messenger RNA (PRKCQ mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
8-Octyl-benzolactam-V9	DM4Z15M	Discovery agent	N.A.	Investigative	[14]
ISIS 109351	DM508BS	Discovery agent	N.A.	Investigative	[31]
ISIS 109352	DMWK1XC	Discovery agent	N.A.	Investigative	[31]
ISIS 109353	DM6AJMC	Discovery agent	N.A.	Investigative	[31]
ISIS 109355	DMFIQGW	Discovery agent	N.A.	Investigative	[31]
4-(1H-indol-6-ylamino)-5-styrylnicotinonitrile	DMB07TU	Discovery agent	N.A.	Investigative	[32]
4-(1H-indol-5-yloxy)-5-styrylnicotinonitrile	DMH360U	Discovery agent	N.A.	Investigative	[32]
ISIS 109354	DM1REKQ	Discovery agent	N.A.	Investigative	[31]
4-(1H-indol-5-ylamino)-5-styrylnicotinonitrile	DMAU0SF	Discovery agent	N.A.	Investigative	[32]
4-(3H-indol-4-ylamino)-5-styrylnicotinonitrile	DMM8AY5	Discovery agent	N.A.	Investigative	[32]

Drug(s) Targeting PKC-epsilon messenger RNA (PRKCE mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BALANOL	DMDLN9E	N. A.	N. A.	Terminated	[7]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[33]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[26]
8-Octyl-benzolactam-V9	DM4Z15M	Discovery agent	N.A.	Investigative	[14]
chelerythrine	DMCP1G9	Discovery agent	N.A.	Investigative	[34]
ISIS 7942	DMN0A1R	Discovery agent	N.A.	Investigative	[15]
ISIS 7948	DMYZE8R	Discovery agent	N.A.	Investigative	[15]

Drug(s) Affected By Interleukin-2 receptor subunit alpha (IL2RA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[35]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[36]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[37]
Acocantherin	DM7JT24	Atrial fibrillation	BC81.3	Approved	[38]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[39]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[40]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[41]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[42]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[43]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[44]

Drug(s) Affected By Early activation antigen CD69 (CD69)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[45]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[46]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[47]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[46]
Lindane	DMB8CNL	Infestations of lice and scabies	1G00.Z	Approved	[46]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[48]
Demecolcine	DMCZQGK	Solid tumour/cancer	2A00-2F9Z	Approved	[49]
Mifepristone	DMGZQEF	Cushing disease	5A70	Approved	[50]
Zoledronate	DMIXC7G	Adenocarcinoma	2D40	Approved	[51]
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[52]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
PKC-delta messenger RNA (PRKCD mRNA)	TT7A1BO	KPCD_HUMAN	Inhibitor	[1]
PKC-epsilon messenger RNA (PRKCE mRNA)	TT57MT2	KPCE_HUMAN	Inhibitor	[1]
PKC-eta messenger RNA (PRKCH mRNA)	TTONI0R	KPCL_HUMAN	Inhibitor	[1]
PKC-theta messenger RNA (PRKCQ mRNA)	TT1MS7X	KPCT_HUMAN	Inhibitor	[1]
Protein kinase C alpha (PRKCA)	TTFJ8Q1	KPCA_HUMAN	Inhibitor	[1]
Protein kinase C beta (PRKCB)	TTYPXQF	KPCB_HUMAN	Inhibitor	[1]
Protein kinase C delta (PRKCD)	TT9WJ8U	KPCD_HUMAN	Inhibitor	[1]
Protein kinase C gamma (PRKCG)	TTRFOXJ	KPCG_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Early activation antigen CD69 (CD69)	OTGJHSVP	CD69_HUMAN	Gene/Protein Processing	[2]
Interleukin-2 receptor subunit alpha (IL2RA)	OT0MWCHG	IL2RA_HUMAN	Gene/Protein Processing	[2]

References

• [1] A nonpromoting phorbol from the samoan medicinal plant Homalanthus nutans inhibits cell killing by HIV-1. J Med Chem. 1992 May 29;35(11):1978-86.
• [2] The BET inhibitor OTX015 reactivates latent HIV-1 through P-TEFb. Sci Rep. 2016 Apr 12;6:24100. doi: 10.1038/srep24100.
• [3] Polo-like kinase inhibitor Ro5203280 has potent antitumor activity in nasopharyngeal carcinoma.Mol Cancer Ther. 2013 Aug;12(8):1393-401.
• [4] Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.
• [5] Cancer stem cell (CSC) inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jul;27(7):753-761.
• [6] Phase II study of PKC-alpha antisense oligonucleotide aprinocarsen in combination with gemcitabine and carboplatin in patients with advanced non-small cell lung cancer.Lung Cancer.2006 May;52(2):173-80.
• [7] Evaluation of differential hypoxic cytotoxicity and electrochemical studies of nitro 5-deazaflavins, Bioorg. Med. Chem. Lett. 5(18):2155-2160 (1995).
• [8] Bisindolylmaleimide inhibitors of protein kinase C. Further conformational restriction of a tertiary amine side chain, Bioorg. Med. Chem. Lett. 4(11):1303-1308 (1994).
• [9] Synthesis of bisindolylmaleimide macrocycles, Bioorg. Med. Chem. Lett. 5(18):2093-2096 (1995).
• [10] Phenylethanoid glycosides from Digitalis purpurea and Penstemon linarioides with PKCalpha-inhibitory activity. J Nat Prod. 1998 Nov;61(11):1410-2.
• [11] Inhibitors of protein kinase C. 1. 2,3-Bisarylmaleimides. J Med Chem. 1992 Jan;35(1):177-84.
• [12] Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
• [13] (S)-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... J Med Chem. 1996 Jul 5;39(14):2664-71.
• [14] Design and synthesis of 8-octyl-benzolactam-V9, a selective activator for protein kinase C epsilon and eta. J Med Chem. 2006 May 4;49(9):2681-8.
• [15] US patent application no. 5,959,096, Antisense oligonucleotides against human protein kinase C.
• [16] The oral protein-kinase C beta inhibitor enzastaurin (LY317615) suppresses signalling through the AKT pathway, inhibits proliferation and induces apoptosis in multiple myeloma cell lines. Leuk Lymphoma. 2008 Jul;49(7):1374-83.
• [17] Ruboxistaurin: LY 333531. Drugs R D. 2007;8(3):193-9.
• [18] Protein kinase C beta inhibition attenuates the progression of experimental diabetic nephropathy in the presence of continued hypertension. Diabetes. 2003 Feb;52(2):512-8.
• [19] ClinicalTrials.gov (NCT03492125) A Study Of The Selective PKC-beta Inhibitor MS- 553. U.S. National Institutes of Health.
• [20] Potential new medical therapies for diabetic retinopathy: protein kinase C inhibitors. Am J Ophthalmol. 2002 May;133(5):693-8.
• [21] PKC delta and epsilon in drug targeting and therapeutics. Recent Pat DNA Gene Seq. 2009;3(2):96-101.
• [22] Novel extranuclear-targeted anthracyclines override the antiapoptotic functions of Bcl-2 and target protein kinase C pathways to induce apoptosis. Mol Cancer Ther. 2002 May;1(7):469-81.
• [23] Novel protein kinase C inhibitors: synthesis and PKC inhibition of beta-substituted polythiophene derivatives. Bioorg Med Chem Lett. 1999 Aug 2;9(15):2279-82.
• [24] Multivariate analysis by the minimum spanning tree method of the structural determinants of diphenylethylenes and triphenylacrylonitriles implicate... J Med Chem. 1992 Feb 7;35(3):573-83.
• [25] A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
• [26] Protein kinase C epsilon regulates gamma-aminobutyrate type A receptor sensitivity to ethanol and benzodiazepines through phosphorylation of gamma2... J Biol Chem. 2007 Nov 9;282(45):33052-63.
• [27] Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81.
• [28] Inhibition of protein kinase C mu by various inhibitors. Differentiation from protein kinase c isoenzymes. FEBS Lett. 1996 Aug 26;392(2):77-80.
• [29] Design, synthesis, and biological activity of isophthalic acid derivatives targeted to the C1 domain of protein kinase C. J Med Chem. 2009 Jul 9;52(13):3969-81.
• [30] US patent application no. 6,235,723, Antisense oligonucleotide modulation of human protein kinase C-.delta. expression.
• [31] US patent application no. 6,190,869, Antisense inhibition of protein kinase C-theta expression.
• [32] First generation 5-vinyl-3-pyridinecarbonitrile PKCtheta inhibitors. Bioorg Med Chem Lett. 2009 Oct 15;19(20):5829-32.
• [33] Synthesis of anilino-monoindolylmaleimides as potent and selective PKCbeta inhibitors. Bioorg Med Chem Lett. 2004 Oct 18;14(20):5171-4.
• [34] A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8.
• [35] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [36] Simvastatin inhibits IL-17 secretion by targeting multiple IL-17-regulatory cytokines and by inhibiting the expression of IL-17 transcription factor RORC in CD4+ lymphocytes. J Immunol. 2008 May 15;180(10):6988-96. doi: 10.4049/jimmunol.180.10.6988.
• [37] Down-regulation of interleukin-2 receptor gene activation and protein expression by dideoxynucleoside analogs. Cell Immunol. 1995 Jul;163(2):289-95. doi: 10.1006/cimm.1995.1128.
• [38] Ouabain induces inhibition of the progression phase in human T-cell proliferation. J Cell Physiol. 1995 Nov;165(2):246-53. doi: 10.1002/jcp.1041650205.
• [39] 1,25-Dihydroxyvitamin D3-regulated expression of genes involved in human T-lymphocyte proliferation and differentiation. Cancer Res. 1986 Nov;46(11):5827-31.
• [40] Pimecrolimus inhibits up-regulation of OX40 and synthesis of inflammatory cytokines upon secondary T cell activation by allogeneic dendritic cells. Clin Exp Immunol. 2002 Oct;130(1):85-92. doi: 10.1046/j.1365-2249.2002.01962.x.
• [41] Effects of different anaesthetic agents on immune cell function in vitro. Eur J Anaesthesiol. 2005 Aug;22(8):616-23. doi: 10.1017/s0265021505001031.
• [42] Differential effects of statins on relevant functions of human monocyte-derived dendritic cells. J Leukoc Biol. 2006 Mar;79(3):529-38. doi: 10.1189/jlb.0205064. Epub 2005 Dec 30.
• [43] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [44] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [45] 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.
• [46] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [47] Cannabis-induced cytotoxicity in leukemic cell lines: the role of the cannabinoid receptors and the MAPK pathway. Blood. 2005 Feb 1;105(3):1214-21. doi: 10.1182/blood-2004-03-1182. Epub 2004 Sep 28.
• [48] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [49] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [50] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [51] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [52] Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation. Blood. 2008 Feb 1;111(3):1366-77. doi: 10.1182/blood-2007-04-084814. Epub 2007 Oct 25.