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

General Information of Drug (ID: DM8IYG1)

• Drug Name: 4-[1-(4-hydroxyphenyl)-3-methyl-1-butenyl]phenol Drug Info
• Synonyms: Phenol, 4,4'-(3-methyl-1-butenylidene)bis-; 66422-07-9; CHEMBL156843; CTK1J4765; DTXSID70441143; ZINC13650255

Indication

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

• Cross-matching ID:
  PubChem CID: 10515117
  CAS Number: CAS 66422-07-9
  TTD Drug ID: DM8IYG1

Molecule-Related Drug Atlas

Drug(s) Targeting Protein kinase C epsilon (PRKCE)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Meprobamate	DMHM93Y	Anxiety		Approved	[2]
Bryostatin-1	DM1JOXY	Alzheimer disease	8A20	Phase 2	[3]
RO-320432	DMFZ1YW	N. A.	N. A.	Terminated	[4]
LY-317644	DMM20PI	N. A.	N. A.	Terminated	[5]
CDE-6960	DMA0DKI	Inflammation	1A00-CA43.1	Terminated	[6]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[7]
3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione	DMDO175	Discovery agent	N.A.	Investigative	[8]
3,4-diphenyl-1H-pyrrole-2,5-dione	DMPK6YT	Discovery agent	N.A.	Investigative	[8]
3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione	DMGC7RY	Discovery agent	N.A.	Investigative	[8]
3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione	DM3EV9N	Discovery agent	N.A.	Investigative	[8]

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	[9]
Sotrastaurin acetate	DME53YS	Renal transplantation	NE84	Phase 2	[10]
PMID28460551-Compound-3	DMA1FRM	N. A.	N. A.	Patented	[11]
ISIS 3521	DMZFS69	N. A.	N. A.	Discontinued in Phase 2	[12]
BALANOL	DMDLN9E	N. A.	N. A.	Terminated	[13]
RO-320432	DMFZ1YW	N. A.	N. A.	Terminated	[4]
LY-317644	DMM20PI	N. A.	N. A.	Terminated	[5]
Acteoside	DM0YHKB	Nephritis	GB40	Terminated	[14]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[7]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[15]

Drug(s) Targeting Protein kinase C theta (PRKCQ)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sotrastaurin acetate	DME53YS	Renal transplantation	NE84	Phase 2	[10]
RO-320432	DMFZ1YW	N. A.	N. A.	Terminated	[4]
LY-317644	DMM20PI	N. A.	N. A.	Terminated	[5]
CDE-6960	DMA0DKI	Inflammation	1A00-CA43.1	Terminated	[6]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[7]
LY-326449	DMN53M4	Discovery agent	N.A.	Investigative	[16]
L-serine-O-phosphate	DMTJ1NH	Discovery agent	N.A.	Investigative	[17]
[2,2':5',2'']Terthiophen-4-yl-methanol	DMRQC1F	Discovery agent	N.A.	Investigative	[18]
2-(4-Hydroxy-phenyl)-3,3-diphenyl-acrylonitrile	DMNGW1A	Discovery agent	N.A.	Investigative	[1]
[2,2':5',2'']Terthiophene-4,5''-dicarbaldehyde	DMWDNLI	Discovery agent	N.A.	Investigative	[18]

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	[19]
RUBOXISTAURIN HYDROCHLORIDE	DMQOCD8	Lymphoma	2A80-2A86	Phase 3	[20]
Sotrastaurin acetate	DME53YS	Renal transplantation	NE84	Phase 2	[10]
LY333531	DMGMC8H	Solid tumour/cancer	2A00-2F9Z	Phase 2	[21]
MS-553	DM7ER9J	Chronic lymphocytic leukaemia	2A82.0	Phase 1	[22]
Linetastine	DMF8B62	Rhinitis	FA20	Discontinued in Phase 2	[23]
BALANOL	DMDLN9E	N. A.	N. A.	Terminated	[13]
RO-320432	DMFZ1YW	N. A.	N. A.	Terminated	[4]
LY-317644	DMM20PI	N. A.	N. A.	Terminated	[5]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[7]

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	[24]
RO-320432	DMFZ1YW	N. A.	N. A.	Terminated	[4]
LY-317644	DMM20PI	N. A.	N. A.	Terminated	[5]
AD 198	DMJFY2I	N. A.	N. A.	Terminated	[25]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[7]
LY-326449	DMN53M4	Discovery agent	N.A.	Investigative	[16]
PROSTRATIN	DM1HMJ5	Human immunodeficiency virus infection	1C62	Investigative	[26]
[2,2':5',2'']Terthiophen-4-yl-methanol	DMRQC1F	Discovery agent	N.A.	Investigative	[18]
2-(4-Hydroxy-phenyl)-3,3-diphenyl-acrylonitrile	DMNGW1A	Discovery agent	N.A.	Investigative	[1]
[2,2':5',2'']Terthiophene-4,5''-dicarbaldehyde	DMWDNLI	Discovery agent	N.A.	Investigative	[18]

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	[27]
BALANOL	DMDLN9E	N. A.	N. A.	Terminated	[13]
RO-320432	DMFZ1YW	N. A.	N. A.	Terminated	[4]
LY-317644	DMM20PI	N. A.	N. A.	Terminated	[5]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[7]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[28]
3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione	DMDO175	Discovery agent	N.A.	Investigative	[8]
3,4-diphenyl-1H-pyrrole-2,5-dione	DMPK6YT	Discovery agent	N.A.	Investigative	[8]
3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione	DMGC7RY	Discovery agent	N.A.	Investigative	[8]
3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione	DM3EV9N	Discovery agent	N.A.	Investigative	[8]

Drug(s) Targeting Protein kinase C zeta (PRKCZ)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methyl 2-amino-4-phenylthiophene-3-carboxylate	DM9BYJ0	N. A.	N. A.	Patented	[29]
Y-9680	DMHAVYS	N. A.	N. A.	Patented	[29]
US8889696, 39	DMKXRJ4	N. A.	N. A.	Patented	[30]
US8889672, 252-036-001	DM8B1Q4	N. A.	N. A.	Patented	[29]
RO-320432	DMFZ1YW	N. A.	N. A.	Terminated	[4]
LY-317644	DMM20PI	N. A.	N. A.	Terminated	[5]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[7]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[31]
LY-326449	DMN53M4	Discovery agent	N.A.	Investigative	[16]
[2,2':5',2'']Terthiophen-4-yl-methanol	DMRQC1F	Discovery agent	N.A.	Investigative	[18]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
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 epsilon (PRKCE)	TTBZ7OD	KPCE_HUMAN	Inhibitor	[1]
Protein kinase C gamma (PRKCG)	TTRFOXJ	KPCG_HUMAN	Inhibitor	[1]
Protein kinase C theta (PRKCQ)	TT8QL1J	KPCT_HUMAN	Inhibitor	[1]
Protein kinase C zeta (PRKCZ)	TTUWGRA	KPCZ_HUMAN	Inhibitor	[1]

References

• [1] 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.
• [2] Protein kinase C, an elusive therapeutic target . Nat Rev Drug Discov. 2012 December; 11(12): 937-957.
• [3] Protein kinase epsilon dampens the secretory response of model intestinal epithelia during ischemia. Surgery. 2001 Aug;130(2):310-8.
• [4] Bisindolylmaleimide inhibitors of protein kinase C. Further conformational restriction of a tertiary amine side chain, Bioorg. Med. Chem. Lett. 4(11):1303-1308 (1994).
• [5] Synthesis of bisindolylmaleimide macrocycles, Bioorg. Med. Chem. Lett. 5(18):2093-2096 (1995).
• [6] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025002)
• [7] Inhibitors of protein kinase C. 1. 2,3-Bisarylmaleimides. J Med Chem. 1992 Jan;35(1):177-84.
• [8] Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81.
• [9] Polo-like kinase inhibitor Ro5203280 has potent antitumor activity in nasopharyngeal carcinoma.Mol Cancer Ther. 2013 Aug;12(8):1393-401.
• [10] Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.
• [11] Cancer stem cell (CSC) inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jul;27(7):753-761.
• [12] 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.
• [13] Evaluation of differential hypoxic cytotoxicity and electrochemical studies of nitro 5-deazaflavins, Bioorg. Med. Chem. Lett. 5(18):2155-2160 (1995).
• [14] Phenylethanoid glycosides from Digitalis purpurea and Penstemon linarioides with PKCalpha-inhibitory activity. J Nat Prod. 1998 Nov;61(11):1410-2.
• [15] Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
• [16] (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.
• [17] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [18] 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.
• [19] 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.
• [20] Ruboxistaurin: LY 333531. Drugs R D. 2007;8(3):193-9.
• [21] 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.
• [22] ClinicalTrials.gov (NCT03492125) A Study Of The Selective PKC-beta Inhibitor MS- 553. U.S. National Institutes of Health.
• [23] Potential new medical therapies for diabetic retinopathy: protein kinase C inhibitors. Am J Ophthalmol. 2002 May;133(5):693-8.
• [24] PKC delta and epsilon in drug targeting and therapeutics. Recent Pat DNA Gene Seq. 2009;3(2):96-101.
• [25] 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.
• [26] 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.
• [27] 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.
• [28] 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.
• [29] Compounds, formulations, and methods of protein kinase C inhibition. US8889672.
• [30] Substituted pyrido[2,3-d]pyrimidin-7(8H)-ones and therapeutic uses thereof. US8889696.
• [31] Protein kinase C zeta isoform is critical for proliferation in human glioblastoma cell lines. J Neurooncol. 2000 Apr;47(2):109-15.