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

General Information of Drug (ID: DMDJLF0)

• Drug Name: Ro31-8220 Drug Info
• Synonyms: Bisindolylmaleimide IX; ro 31-8220; bisindolylmaleimide IX; 125314-64-9; Ro 31 8220; Ro 318220; UNII-W9A0B5E78O; Ro-318220; Ro-31-8220; CHEMBL6291; W9A0B5E78O; CHEBI:38912; 3-{3-[4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-1H-indol-1-yl}propyl carbamimidothioate; Ro 31-8220 ; 3-{3-[4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-1H-indol-1-yl}propyl imidothiocarbamate; CHEMBL1591531; Carbamimidothioic acid, 3-(3-(2,5-dihydro-4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-1H-pyrrol-3-yl)-1H-indol-1-yl)propyl; Ro 318220; bisindolymaleimide IX; BISINDOLYLMALEIMIDE IX

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1] , [2]

• Cross-matching ID:
  PubChem CID: 5083
  ChEBI ID: CHEBI:38912
  CAS Number: CAS 125314-64-9
  TTD Drug ID: DMDJLF0

Molecule-Related Drug Atlas

Drug(s) Targeting LCK tyrosine protein kinase (LCK)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dasatinib	DMJV2EK	Chronic myelogenous leukaemia	2A20.0	Approved	[4]
VX-680	DM93YKJ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[4]
JNJ-26483327	DMSQ3AZ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
ISIS-CRP	DMQDUG4	Cardiovascular disease	BA00-BE2Z	Phase 1	[6]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[2]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[2]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[7]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[2]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[8]
BMS-536924	DMXJB4N	Discovery agent	N.A.	Investigative	[9]

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	[10]
Sotrastaurin acetate	DME53YS	Renal transplantation	NE84	Phase 2	[11]
PMID28460551-Compound-3	DMA1FRM	N. A.	N. A.	Patented	[12]
ISIS 3521	DMZFS69	N. A.	N. A.	Discontinued in Phase 2	[13]
BALANOL	DMDLN9E	N. A.	N. A.	Terminated	[14]
RO-320432	DMFZ1YW	N. A.	N. A.	Terminated	[15]
LY-317644	DMM20PI	N. A.	N. A.	Terminated	[16]
Acteoside	DM0YHKB	Nephritis	GB40	Terminated	[17]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[18]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[7]

Drug(s) Targeting NAD-dependent deacetylase sirtuin-1 (SIRT1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Resveratrol	DM3RWXL	Giant cell arteritis	4A44.2	Phase 3	[19]
GSK2245840	DMG7YQL	Chronic obstructive pulmonary disease	CA22	Phase 2	[20]
SEN-196	DMLDBQ5	Huntington disease	8A01.10	Phase 2	[21]
MB-12066	DMRSN2C	Obesity	5B81	Phase 2	[22]
SRT2379	DM7DAKX	Type-2 diabetes	5A11	Phase 1	[23]
SRT3025	DMRAXFH	Type-2 diabetes	5A11	Phase 1	[24]
PMID25435179-Compound-WO2012106509Salermide	DMLAH39	N. A.	N. A.	Patented	[19]
CAMBINOL	DMW46GY	Discovery agent	N.A.	Patented	[25]
PMID25435179-Compound-WO2012106509CAY10602	DM2F1T0	N. A.	N. A.	Patented	[19]
PMID25435179-Compound-WO2012106509Tenovin-6	DMBSOED	N. A.	N. A.	Patented	[19]

Drug(s) Targeting Stress-activated protein kinase JNK1 (JNK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NKP-1339	DM5AWK1	Solid tumour/cancer	2A00-2F9Z	Phase 1	[26]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[27]
PMID25991433-Compound-F2	DM37VIQ	N. A.	N. A.	Patented	[27]
7-azaindole derivative 1	DMQL5B7	N. A.	N. A.	Patented	[27]
7-azaindole derivative 5	DMV3H98	N. A.	N. A.	Patented	[27]
PMID25991433-Compound-P6	DMNDVC9	N. A.	N. A.	Patented	[27]
PMID25991433-Compound-J3	DM17P3F	N. A.	N. A.	Patented	[27]
PMID25991433-Compound-P1	DMD8AX6	N. A.	N. A.	Patented	[27]
PMID25991433-Compound-O3	DMVOWS5	N. A.	N. A.	Patented	[27]
PMID25991433-Compound-L1	DM2135Y	N. A.	N. A.	Patented	[27]

Drug(s) Targeting Rho-associated protein kinase 1 (ROCK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Netarsudil	DM0LPI9	Open-angle glaucoma	9C61	Approved	[28]
SAR-407899	DMF95KD	Diabetic nephropathy	GB61.Z	Phase 2	[29]
H-1152	DM8XH3S	Pulmonary arterial hypertension	BB01.0	Phase 2	[30]
INS-117548	DMA46DO	Glaucoma/ocular hypertension	9C61	Phase 1	[31]
GSK269962A	DM5I2HL	Inflammation	1A00-CA43.1	Clinical trial	[32]
PMID28048944-Compound-19	DMPT3V9	N. A.	N. A.	Patented	[33]
PMID28048944-Compound-3	DM1BN74	N. A.	N. A.	Patented	[33]
PMID28048944-Compound-7	DMXZ368	N. A.	N. A.	Patented	[33]
PMID28048944-Compound-4	DMJAUWG	N. A.	N. A.	Patented	[33]
PMID28048944-Compound-5	DMAB987	N. A.	N. A.	Patented	[33]

Drug(s) Targeting Stress-activated protein kinase 2b (p38 beta)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VX-745	DMJAEG6	Alzheimer disease	8A20	Phase 2	[34]
SB 235699	DMNH8XU	Psoriasis vulgaris	EA90	Discontinued in Phase 1	[34]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[2]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[2]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[7]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[2]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[2]
STAUROSPORINONE	DMU2H4K	Discovery agent	N.A.	Investigative	[2]
KT-5720	DM9J50F	Discovery agent	N.A.	Investigative	[2]
L-779450	DM51B74	Discovery agent	N.A.	Investigative	[35]

Drug(s) Targeting Extracellular signal-regulated kinase 2 (ERK2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BVD-523	DMNB4XK	Melanoma	2C30	Phase 2	[36]
HH2710	DM0C5MV	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[37]
ASTX029	DMVZXIA	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[38]
VAN-10-4-eluting stent	DM3ZW6A	Artery stenosis	BD52	Phase 1	[39]
GDC-0994	DMFC2OY	Solid tumour/cancer	2A00-2F9Z	Phase 1	[40]
JSI-1187	DMVJWBS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[41]
LY3214996	DMFDAY7	Solid tumour/cancer	2A00-2F9Z	Phase 1	[42]
CHIR-99021	DMB8MNU	Allergic inflammation	4A80-4A85	Patented	[43]
COR-D	DMLXMCB	T-cell leukaemia	2A90	Preclinical	[44]
SB220025	DMSBUET	Arthritis	FA20	Terminated	[45]

Drug(s) Targeting Stress-activated protein kinase 2a (p38 alpha)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ozagrel	DMIGKA1	Xerophthalmia	5B55.Y	Phase 4	[46]
Losmapimod	DMIL37Z	Acute coronary syndrome	BA41	Phase 3	[46]
VX-702	DMKJDR6	Coronary artery disease	BA80	Phase 2a	[47]
VX-745	DMJAEG6	Alzheimer disease	8A20	Phase 2	[34]
Dilmapimod	DMBYJ92	Acute lung injury	NB32.3	Phase 2	[46]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[27]
PMID25991433-Compound-F2	DM37VIQ	N. A.	N. A.	Patented	[27]
PMID25991433-Compound-L2	DM58UO9	N. A.	N. A.	Patented	[27]
PMID25991433-Compound-L3	DM3LWUR	N. A.	N. A.	Patented	[27]
PMID25991433-Compound-L1	DM2135Y	N. A.	N. A.	Patented	[27]

Drug(s) Targeting RAC-alpha serine/threonine-protein kinase (AKT1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Enzastaurin	DM5H0R9	Diffuse large B-cell lymphoma	2A81	Phase 3	[42]
AZD5363	DM9SKW8	Triple negative breast cancer	2C60-2C65	Phase 3	[42]
GDC-0068	DMWBZJD	Breast cancer	2C60-2C65	Phase 3	[42]
CI-1033	DMSI8N3	Lymphoma	2A80-2A86	Phase 2	[4]
CMX-2043	DMPSCVY	Cardiac disease	BA00-BE2Z	Phase 2	[48]
ARQ 092	DM5WK0J	Proteus syndrome	LD2C	Phase 2	[49]
GSK2110183	DMZHB37	leukaemia	2A60-2B33	Phase 2	[50]
RX-0201	DMTBAV3	Pancreatic cancer	2C10	Phase 2	[51]
Trametinib + 2141795	DMYP7TO	Solid tumour/cancer	2A00-2F9Z	Phase 2	[50]
PTX-200	DM0ZIT2	Breast cancer	2C60-2C65	Phase 2	[42]

Drug(s) Targeting Glycogen synthase kinase-3 beta (GSK-3B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AMO-02	DMJRU3A	Myotonic dystrophy	8C71.0	Phase 2/3	[52]
LY2090314	DMTBFE4	Acute myeloid leukaemia	2A60	Phase 2	[53]
Lithium	DMZ3OU6	Fragile X syndrome	LD55	Phase 2	[54]
Tideglusib	DME4LA1	Osteosarcoma	2B51	Phase 2	[55]
9-ING-41	DM57TY3	Myelofibrosis	2A20.2	Phase 2	[56]
Neu-120	DMXKOUC	Parkinson disease	8A00.0	Phase 1/2	[57]
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[58]
CHIR-99021	DMB8MNU	Allergic inflammation	4A80-4A85	Patented	[43]
TDZD-8	DMG6Q45	Malignant glioma	2A00.0	Patented	[59]
AR-A014418	DMUPN01	Ovarian cancer	2C73	Patented	[60]

Drug(s) Targeting MAP kinase p38 (MAPK12)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SM-101	DMFX9O6	Idiopathic thrombocytopenic purpura	3B64.10	Approved (orphan drug)	[61]
VX-745	DMJAEG6	Alzheimer disease	8A20	Phase 2	[62]
ARRY-797	DMJ48AB	Dilated cardiomyopathy	BC43.0	Phase 2	[63]
KC706	DMBX6C7	Cardiovascular disease	BA00-BE2Z	Discontinued in Phase 2	[64]
SB 235699	DMNH8XU	Psoriasis vulgaris	EA90	Discontinued in Phase 1	[65]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[2]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[2]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[7]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[2]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[8]

Drug(s) Targeting Ribosomal protein S6 kinase beta-1 (S6K1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
M2698	DM3PVBJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[42]
PF-4708671	DMO0892	Ulcerative colitis	DD71	Clinical trial	[66]
PMID27410995-Compound-Figure3c	DMDQMZT	N. A.	N. A.	Patented	[67]
Pyrimido[4,5-d] pyrimidines and pyrido[4,3-d] pyrimidine derivative 1	DM6O2Q9	N. A.	N. A.	Patented	[67]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[2]
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol	DMSKJ1X	Discovery agent	N.A.	Investigative	[68]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[7]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[2]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[2]
STAUROSPORINONE	DMU2H4K	Discovery agent	N.A.	Investigative	[2]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Extracellular signal-regulated kinase 2 (ERK2)	TT4TQBX	MK01_HUMAN	Inhibitor	[2]
Glycogen synthase kinase-3 beta (GSK-3B)	TTRSMW9	GSK3B_HUMAN	Inhibitor	[2]
LCK tyrosine protein kinase (LCK)	TT860QF	LCK_HUMAN	Inhibitor	[2]
MAP kinase p38 (MAPK12)	TTYT93M	MK12_HUMAN	Inhibitor	[2]
NAD-dependent deacetylase sirtuin-1 (SIRT1)	TTUF2HO	SIR1_HUMAN	Inhibitor	[3]
Protein kinase C alpha (PRKCA)	TTFJ8Q1	KPCA_HUMAN	Inhibitor	[2]
RAC-alpha serine/threonine-protein kinase (AKT1)	TTWTSCV	AKT1_HUMAN	Inhibitor	[2]
Rho-associated protein kinase 1 (ROCK1)	TTZN7RP	ROCK1_HUMAN	Inhibitor	[2]
Ribosomal protein S6 kinase beta-1 (S6K1)	TTG0U4H	KS6B1_HUMAN	Inhibitor	[2]
Stress-activated protein kinase 2a (p38 alpha)	TTQBR95	MK14_HUMAN	Inhibitor	[2]
Stress-activated protein kinase 2b (p38 beta)	TT73U6C	MK11_HUMAN	Inhibitor	[2]
Stress-activated protein kinase JNK1 (JNK1)	TT0K6EO	MK08_HUMAN	Inhibitor	[2]

References

• [1] 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: 5259).
• [2] Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
• [3] Adenosine mimetics as inhibitors of NAD+-dependent histone deacetylases, from kinase to sirtuin inhibition. J Med Chem. 2006 Dec 14;49(25):7307-16.
• [4] 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.
• [5] National Cancer Institute Drug Dictionary (drug id 596693).
• [6] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
• [7] Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
• [8] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [9] Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitum... J Med Chem. 2005 Sep 8;48(18):5639-43.
• [10] Polo-like kinase inhibitor Ro5203280 has potent antitumor activity in nasopharyngeal carcinoma.Mol Cancer Ther. 2013 Aug;12(8):1393-401.
• [11] Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.
• [12] Cancer stem cell (CSC) inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jul;27(7):753-761.
• [13] 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.
• [14] Evaluation of differential hypoxic cytotoxicity and electrochemical studies of nitro 5-deazaflavins, Bioorg. Med. Chem. Lett. 5(18):2155-2160 (1995).
• [15] Bisindolylmaleimide inhibitors of protein kinase C. Further conformational restriction of a tertiary amine side chain, Bioorg. Med. Chem. Lett. 4(11):1303-1308 (1994).
• [16] Synthesis of bisindolylmaleimide macrocycles, Bioorg. Med. Chem. Lett. 5(18):2093-2096 (1995).
• [17] Phenylethanoid glycosides from Digitalis purpurea and Penstemon linarioides with PKCalpha-inhibitory activity. J Nat Prod. 1998 Nov;61(11):1410-2.
• [18] Inhibitors of protein kinase C. 1. 2,3-Bisarylmaleimides. J Med Chem. 1992 Jan;35(1):177-84.
• [19] Sirtuin modulators: an updated patent review (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):5-15.
• [20] Sirtuin 1 activator SRT2104 protects Huntington's disease mice. Ann Clin Transl Neurol. 2014 Dec;1(12):1047-52.
• [21] Sirtuin 1 (SIRT1): the misunderstood HDAC. J Biomol Screen. 2011 Dec;16(10):1153-69.
• [22] Pharmacological activation of Sirt1 ameliorates polyglutamine-induced toxicity through the regulation of autophagy.PLoS One.2013 Jun 10;8(6):e64953.
• [23] SRT2379, a small-molecule SIRT1 activator, fails to reduce cytokine release in a human endotoxemia model. Critical Care 2013, 17(Suppl 4):P8.
• [24] The Sirt1 Activators SRT2183 and SRT3025 Inhibit RANKL-Induced Osteoclastogenesis in Bone Marrow-Derived Macrophages and Down-Regulate Sirt3 in Sirt1 Null Cells. PLoS One. 2015 Jul 30;10(7):e0134391.
• [25] Novel cambinol analogs as sirtuin inhibitors: synthesis, biological evaluation, and rationalization of activity. J Med Chem. 2009 May 14;52(9):2673-82.
• [26] 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: 1496).
• [27] c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
• [28] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [29] The Rho kinase inhibitor SAR407899 potently inhibits endothelin-1-induced constriction of renal resistance arteries. J Hypertens. 2012 May;30(5):980-9.
• [30] Emerging treatments for pulmonary arterial hypertension. Expert Opin Emerg Drugs. 2006 Nov;11(4):609-19.
• [31] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [32] Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther. 2007 Jan;320(1):89-98.
• [33] Rho kinase inhibitors: a patent review (2014 - 2016).Expert Opin Ther Pat. 2017 Apr;27(4):507-515.
• [34] Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
• [35] The identification of potent and selective imidazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett. 2006 Jan 15;16(2):378-81.
• [36] DOI: 10.1158/1538-7445.AM2015-4693
• [37] Clinical pipeline report, company report or official report of HaiHe Biopharma.
• [38] Clinical pipeline report, company report or official report of Astex Pharmaceuticals.
• [39] WO patent application no. 2013,1850,32, Nanotherapeutics for drug targeting.
• [40] ERK Mutations Confer Resistance to Mitogen-Activated Protein Kinase Pathway Inhibitors
• [41] National Cancer Institute Drug Dictionary (drug name JSI1187).
• [42] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [43] Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95.
• [44] Corchorusin-D directed apoptosis of K562 cells occurs through activation of mitochondrial and death receptor pathways and suppression of AKT/PKB pathway. Cell Physiol Biochem. 2012;30(4):915-26.
• [45] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [46] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [47] Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies. Arthritis Rheum. 2009 May;60(5):1232-41.
• [48] Pre-clinical and Clinical Safety Studies of CMX-2043: a cytoprotective lipoic acid analogue for ischaemia-reperfusion injury. Basic Clin Pharmacol Toxicol. 2014 Nov;115(5):456-64.
• [49] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [50] 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: 1479).
• [51] CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008.
• [52] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [53] Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015).Expert Opin Ther Pat. 2017 Jun;27(6):657-666.
• [54] The GSK3 kinase inhibitor lithium produces unexpected hyperphosphorylation of -catenin, a GSK3 substrate, in human glioblastoma cells. Biol Open. 2018 Jan 26;7(1):bio030874.
• [55] Evidence for irreversible inhibition of glycogen synthase kinase-3beta by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904.
• [56] 9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer. Sci Rep. 2019 Dec 27;9(1):19977.
• [57] Company report (Neurim Pharmaceuticals)
• [58] 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.
• [59] Identification of novel scaffold of benzothiazepinones as non-ATP competitive glycogen synthase kinase-3beta inhibitors through virtual screening. Bioorg Med Chem Lett. 2012 Dec 1;22(23):7232-6.
• [60] Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models. Eur J Med Chem. 2009 Jun;44(6):2361-71.
• [61] Agents in development for the treatment of diabetic nephropathy. Expert Opin Emerg Drugs. 2008 Sep;13(3):447-63.
• [62] P38 MAP kinase inhibitors as potential therapeutics for the treatment of joint degeneration and pain associated with osteoarthritis. J Inflamm (Lond). 2008 Dec 4;5:22.
• [63] Array BioPharmas ARRY-797 Meets Primary Endpoint in Clinical Proof of Concept Trial in Osteoarthritis Patients Whose Pain is Poorly Controlled by NSAIDs
• [64] KC706, an Oral p38 MAP Kinase Inhibitor, Increases HDL-C. Circulation. 2007;116:II_126.
• [65] Synthesis and structure-activity relationship of aminobenzophenones. A novel class of p38 MAP kinase inhibitors with high antiinflammatory activity. J Med Chem. 2003 Dec 18;46(26):5651-62.
• [66] Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1). Biochem J. 2010 Oct 15;431(2):245-55.
• [67] Ribosomal S6 kinase (RSK) modulators: a patent review.Expert Opin Ther Pat. 2016 Sep;26(9):1061-78.
• [68] 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem. 2006 Nov 2;49(22):6500-9.