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

General Information of Drug (ID: DMN9YOB)

• Drug Name: 4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole Drug Info
• Synonyms: 4,5,6,7-tetrabromobenzotriazole

Indication

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

• Cross-matching ID:
  PubChem CID: 1694
  CAS Number: CAS 17374-26-4
  TTD Drug ID: DMN9YOB

Molecule-Related Drug Atlas

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		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	[7]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[7]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[7]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[8]
BMS-536924	DMXJB4N	Discovery agent	N.A.	Investigative	[9]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[7]

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]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[7]

Drug(s) Targeting ERK activator kinase 1 (MEK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Selumetinib	DMC7W6R	Neurofibromatosis type 1	LD2D.10	Phase 3	[19]
Diamidothiazole derivative 1	DM02V5Q	N. A.	N. A.	Patented	[20]
Pyridic ketone derivative 1	DM3GU7K	N. A.	N. A.	Patented	[21]
RDEA-436	DM0ILRU	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[22]
DEBROMOHYMENIALDISINE	DMDLER8	Discovery agent	N.A.	Investigative	[23]
REVERSINE	DMWDNOK	Discovery agent	N.A.	Investigative	[24]
OROIDIN	DMA2DQT	Discovery agent	N.A.	Investigative	[23]
PD98059	DMZC90M	Cardiac arrest	MC82	Investigative	[25]
4,5-Dibromo-1H-pyrrole-2-carboxylic acid amide	DMDM9UV	Discovery agent	N.A.	Investigative	[23]
5-phenylamino-4-cyano-3-hydroxy-isothiazole	DMX6R0H	Discovery agent	N.A.	Investigative	[26]

Drug(s) Targeting AMP-activated protein kinase (AMPK)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acadesine	DM1RMF5	Diabetic complication	5A2Y	Phase 3	[27]
MB-11055	DM3RBJW	Fatty liver disease	DB92.Z	Phase 2	[28]
Imeglimin	DMMQFG2	Diabetic complication	5A2Y	Phase 2	[29]
PXL-770	DMNSRY7	Non-alcoholic fatty liver disease	DB92	Phase 2	[30]
ENERGI-F701	DMMIHSO	Alopecia	ED70	Phase 2	[31]
O-304	DMXM34I	Type 2 diabetes	5A11	Phase 2	[32]
IM156	DM4MY9C	Solid tumour/cancer	2A00-2F9Z	Phase 1	[19]
Phenformin	DMQ52JG	Diabetic complication	5A2Y	Withdrawn from market	[33]
PMID23639540C13a	DMLXOAQ	Discovery agent	N.A.	Investigative	[34]
SU 6656	DMF1P6W	Discovery agent	N.A.	Investigative	[6]

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	[35]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[36]
PMID25991433-Compound-F2	DM37VIQ	N. A.	N. A.	Patented	[36]
7-azaindole derivative 1	DMQL5B7	N. A.	N. A.	Patented	[36]
7-azaindole derivative 5	DMV3H98	N. A.	N. A.	Patented	[36]
PMID25991433-Compound-P6	DMNDVC9	N. A.	N. A.	Patented	[36]
PMID25991433-Compound-J3	DM17P3F	N. A.	N. A.	Patented	[36]
PMID25991433-Compound-P1	DMD8AX6	N. A.	N. A.	Patented	[36]
PMID25991433-Compound-O3	DMVOWS5	N. A.	N. A.	Patented	[36]
PMID25991433-Compound-L1	DM2135Y	N. A.	N. A.	Patented	[36]

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	[37]
SAR-407899	DMF95KD	Diabetic nephropathy	GB61.Z	Phase 2	[38]
H-1152	DM8XH3S	Pulmonary arterial hypertension	BB01.0	Phase 2	[39]
INS-117548	DMA46DO	Glaucoma/ocular hypertension	9C61	Phase 1	[40]
GSK269962A	DM5I2HL	Inflammation	1A00-CA43.1	Clinical trial	[41]
PMID28048944-Compound-19	DMPT3V9	N. A.	N. A.	Patented	[42]
PMID28048944-Compound-3	DM1BN74	N. A.	N. A.	Patented	[42]
PMID28048944-Compound-7	DMXZ368	N. A.	N. A.	Patented	[42]
PMID28048944-Compound-4	DMJAUWG	N. A.	N. A.	Patented	[42]
PMID28048944-Compound-5	DMAB987	N. A.	N. A.	Patented	[42]

Drug(s) Targeting Casein kinase II alpha (CSNK2A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CX-4945	DMWE7B9	Coronavirus infection	1D92	Phase 2	[19]
BALANOL	DMDLN9E	N. A.	N. A.	Terminated	[43]
EMODIN	DMAEDQG	Coronavirus Disease 2019 (COVID-19)	1D6Y	Terminated	[2]
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol	DMSKJ1X	Discovery agent	N.A.	Investigative	[44]
ELLAGIC ACID	DMX8BS5	Discovery agent	N.A.	Investigative	[2]
APIGENIN	DMI3491	Discovery agent	N.A.	Investigative	[2]
PMID24900749C1a	DMZPUSO	Discovery agent	N.A.	Investigative	[45]
AdoC(Dpr)2AlaArg6	DM2TWSZ	Discovery agent	N.A.	Investigative	[46]
PMID22115617C2c	DMX5UKA	Discovery agent	N.A.	Investigative	[47]
5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole	DM3JB6S	Discovery agent	N.A.	Investigative	[2]

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	[48]
SB 235699	DMNH8XU	Psoriasis vulgaris	EA90	Discontinued in Phase 1	[48]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[7]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[7]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[7]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[7]
Ro31-8220	DMDJLF0	Discovery agent	N.A.	Investigative	[7]
STAUROSPORINONE	DMU2H4K	Discovery agent	N.A.	Investigative	[7]
KT-5720	DM9J50F	Discovery agent	N.A.	Investigative	[7]
L-779450	DM51B74	Discovery agent	N.A.	Investigative	[49]

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	[50]
HH2710	DM0C5MV	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[51]
ASTX029	DMVZXIA	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[52]
VAN-10-4-eluting stent	DM3ZW6A	Artery stenosis	BD52	Phase 1	[53]
GDC-0994	DMFC2OY	Solid tumour/cancer	2A00-2F9Z	Phase 1	[54]
JSI-1187	DMVJWBS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[55]
LY3214996	DMFDAY7	Solid tumour/cancer	2A00-2F9Z	Phase 1	[19]
CHIR-99021	DMB8MNU	Allergic inflammation	4A80-4A85	Patented	[56]
COR-D	DMLXMCB	T-cell leukaemia	2A90	Preclinical	[57]
SB220025	DMSBUET	Arthritis	FA20	Terminated	[58]

Drug(s) Targeting Checkpoint kinase-1 (CHK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LY2603618	DMCXRZF	Pancreatic cancer	2C10	Phase 2	[59]
UCN-01	DMUNJZB	Non-small-cell lung cancer	2C25.Y	Phase 2	[60]
SCH-900776	DM67EMK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[61]
LY2606368	DM4XMF7	Ovarian cancer	2C73	Phase 2	[19]
LY2880070	DMADEHZ	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[62]
RG7741	DMK6P9J	Lymphoma	2A80-2A86	Phase 1	[63]
GDC-0425	DMDZ26X	Lymphoma	2A80-2A86	Phase 1	[64]
AZD7762	DM1FW0C	Solid tumour/cancer	2A00-2F9Z	Phase 1	[65]
MK-8776	DMAS1RB	Hodgkin lymphoma	2B30	Phase 1	[66]
Diamidothiazole derivative 1	DM02V5Q	N. A.	N. A.	Patented	[20]

Drug(s) Targeting Serine/threonine-protein kinase Sgk1 (SGK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[7]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[7]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[7]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[7]
CGP-57380	DMFPOUC	Discovery agent	N.A.	Investigative	[6]
GSK-650394	DMNRP2L	Prostate cancer	2C82.0	Investigative	[67]

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	[68]
Losmapimod	DMIL37Z	Acute coronary syndrome	BA41	Phase 3	[68]
VX-702	DMKJDR6	Coronary artery disease	BA80	Phase 2a	[69]
VX-745	DMJAEG6	Alzheimer disease	8A20	Phase 2	[48]
Dilmapimod	DMBYJ92	Acute lung injury	NB32.3	Phase 2	[68]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[36]
PMID25991433-Compound-F2	DM37VIQ	N. A.	N. A.	Patented	[36]
PMID25991433-Compound-L2	DM58UO9	N. A.	N. A.	Patented	[36]
PMID25991433-Compound-L3	DM3LWUR	N. A.	N. A.	Patented	[36]
PMID25991433-Compound-L1	DM2135Y	N. A.	N. A.	Patented	[36]

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	[19]
Enzastaurin	DM5H0R9	Diffuse large B-cell lymphoma	2A81	Phase 3	[19]
GDC-0068	DMWBZJD	Breast cancer	2C60-2C65	Phase 3	[19]
CI-1033	DMSI8N3	Lymphoma	2A80-2A86	Phase 2	[4]
CMX-2043	DMPSCVY	Cardiac disease	BA00-BE2Z	Phase 2	[70]
ARQ 092	DM5WK0J	Proteus syndrome	LD2C	Phase 2	[71]
GSK2110183	DMZHB37	leukaemia	2A60-2B33	Phase 2	[72]
RX-0201	DMTBAV3	Pancreatic cancer	2C10	Phase 2	[73]
PTX-200	DM0ZIT2	Breast cancer	2C60-2C65	Phase 2	[19]
Triciribine prodrug	DMBN1XS	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[72]

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	[74]
LY2090314	DMTBFE4	Acute myeloid leukaemia	2A60	Phase 2	[75]
Lithium	DMZ3OU6	Bipolar disorder	6A60	Phase 2	[76]
Tideglusib	DME4LA1	Alzheimer disease	8A20	Phase 2	[77]
9-ING-41	DM57TY3	Myelofibrosis	2A20.2	Phase 2	[78]
Neu-120	DMXKOUC	Parkinson disease	8A00.0	Phase 1/2	[79]
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[80]
CHIR-99021	DMB8MNU	Allergic inflammation	4A80-4A85	Patented	[56]
TDZD-8	DMG6Q45	Malignant glioma	2A00.0	Patented	[81]
AR-A014418	DMUPN01	Ovarian cancer	2C73	Patented	[82]

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)	[83]
VX-745	DMJAEG6	Alzheimer disease	8A20	Phase 2	[84]
ARRY-797	DMJ48AB	Dilated cardiomyopathy	BC43.0	Phase 2	[85]
KC706	DMBX6C7	Cardiovascular disease	BA00-BE2Z	Discontinued in Phase 2	[86]
SB 235699	DMNH8XU	Psoriasis vulgaris	EA90	Discontinued in Phase 1	[87]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[7]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[7]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[7]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[8]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[7]

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	[19]
NNI-362	DMPCV65	Alzheimer disease	8A20	Phase 1	[88]
PF-4708671	DMO0892	Ulcerative colitis	DD71	Clinical trial	[89]
PMID27410995-Compound-Figure3c	DMDQMZT	N. A.	N. A.	Patented	[90]
Pyrimido[4,5-d] pyrimidines and pyrido[4,3-d] pyrimidine derivative 1	DM6O2Q9	N. A.	N. A.	Patented	[90]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[7]
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol	DMSKJ1X	Discovery agent	N.A.	Investigative	[44]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[7]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[7]
Ro31-8220	DMDJLF0	Discovery agent	N.A.	Investigative	[7]

Drug(s) Affected By RING-box protein 2 (RNF7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[91]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[92]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[93]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[94]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[95]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[96]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[97]
Milchsaure	DM462BT	Pruritus	EC90	Investigative	[98]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
AMP-activated protein kinase (AMPK)	TTLAFZV	AAPK1_HUMAN; AAKB1_HUMAN; AAKG1_HUMAN	Inhibitor	[1]
Casein kinase II alpha (CSNK2A1)	TTER6YH	CSK21_HUMAN	Inhibitor	[2]
Checkpoint kinase-1 (CHK1)	TTTU902	CHK1_HUMAN	Inhibitor	[1]
ERK activator kinase 1 (MEK1)	TTIDAPM	MP2K1_HUMAN	Inhibitor	[1]
Extracellular signal-regulated kinase 2 (ERK2)	TT4TQBX	MK01_HUMAN	Inhibitor	[1]
Glycogen synthase kinase-3 beta (GSK-3B)	TTRSMW9	GSK3B_HUMAN	Inhibitor	[1]
LCK tyrosine protein kinase (LCK)	TT860QF	LCK_HUMAN	Inhibitor	[1]
MAP kinase p38 (MAPK12)	TTYT93M	MK12_HUMAN	Inhibitor	[1]
Protein kinase C alpha (PRKCA)	TTFJ8Q1	KPCA_HUMAN	Inhibitor	[1]
RAC-alpha serine/threonine-protein kinase (AKT1)	TTWTSCV	AKT1_HUMAN	Inhibitor	[1]
Rho-associated protein kinase 1 (ROCK1)	TTZN7RP	ROCK1_HUMAN	Inhibitor	[1]
Ribosomal protein S6 kinase beta-1 (S6K1)	TTG0U4H	KS6B1_HUMAN	Inhibitor	[1]
Serine/threonine-protein kinase Sgk1 (SGK1)	TTTV8EJ	SGK1_HUMAN	Inhibitor	[1]
Stress-activated protein kinase 2a (p38 alpha)	TTQBR95	MK14_HUMAN	Inhibitor	[1]
Stress-activated protein kinase 2b (p38 beta)	TT73U6C	MK11_HUMAN	Inhibitor	[1]
Stress-activated protein kinase JNK1 (JNK1)	TT0K6EO	MK08_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
RING-box protein 2 (RNF7)	OTMDBLP4	RBX2_HUMAN	Post-Translational Modifications	[3]

References

• [1] Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
• [2] Structural insight into human CK2alpha in complex with the potent inhibitor ellagic acid. Bioorg Med Chem Lett. 2009 Jun 1;19(11):2920-3.
• [3] CK2 phosphorylation of SAG at Thr10 regulates SAG stability, but not its E3 ligase activity. Mol Cell Biochem. 2007 Jan;295(1-2):179-88. doi: 10.1007/s11010-006-9287-3. Epub 2006 Jul 28.
• [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] Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
• [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] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [20] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
• [21] MEK inhibitors in oncology: a patent review (2015-Present).Expert Opin Ther Pat. 2017 Aug;27(8):887-906.
• [22] Clinical pipeline report, company report or official report of MedKoo Biosciences.
• [23] Aldisine alkaloids from the Philippine sponge Stylissa massa are potent inhibitors of mitogen-activated protein kinase kinase-1 (MEK-1). J Med Chem. 2002 Jan 17;45(2):529-32.
• [24] Reversine increases the plasticity of lineage-committed mammalian cells. Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10482-7.
• [25] The MEK1 inhibitor PD98059 sensitizes C8161 melanoma cells to cisplatin-induced apoptosis. Melanoma Res. 2001 Feb;11(1):11-9.
• [26] Discovery of 3-hydroxy-4-carboxyalkylamidino-5-arylamino-isothiazoles as potent MEK1 inhibitors. Bioorg Med Chem Lett. 2006 Aug 1;16(15):3975-80.
• [27] Acadesine, an adenosine-regulating agent with the potential for widespread indications. Expert Opin Pharmacother. 2008 Aug;9(12):2137-44.
• [28] Antidiabetes and antiobesity effect of cryptotanshinone via activation of AMP-activated protein kinase.Mol Pharmacol.2007 Jul;72(1):62-72.
• [29] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032542)
• [30] Clinical pipeline report, company report or official report of Poxel SA.
• [31] Clinical pipeline report, company report or official report of Energenesis Biomedical.
• [32] Clinical pipeline report, company report or official report of Betagenon.
• [33] Complementary regulation of TBC1D1 and AS160 by growth factors, insulin and AMPK activators. Biochem J. 2008 Jan 15;409(2):449-59.
• [34] Synthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo[1.5-a]pyrimidine scaffold of dorsomorphin: the discovery of ML347 as an ALK2 versus ALK3 selective MLPCN probe. Bioorg Med Chem Lett. 2013 Jun 1;23(11):3248-52.
• [35] 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).
• [36] c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
• [37] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [38] The Rho kinase inhibitor SAR407899 potently inhibits endothelin-1-induced constriction of renal resistance arteries. J Hypertens. 2012 May;30(5):980-9.
• [39] Emerging treatments for pulmonary arterial hypertension. Expert Opin Emerg Drugs. 2006 Nov;11(4):609-19.
• [40] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [41] Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther. 2007 Jan;320(1):89-98.
• [42] Rho kinase inhibitors: a patent review (2014 - 2016).Expert Opin Ther Pat. 2017 Apr;27(4):507-515.
• [43] Synthesis and protein kinase C inhibitory activities of acyclic balanol analogs that are highly selective for protein kinase C over protein kinase A. J Med Chem. 1996 Dec 20;39(26):5215-27.
• [44] 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.
• [45] Structure and Property Based Design of Pyrazolo[1,5-a]pyrimidine Inhibitors of CK2 Kinase with Activity in Vivo. ACS Med Chem Lett. 2013 Jul 3;4(8):800-5.
• [46] Adenosine-5'-carboxylic acid peptidyl derivatives as inhibitors of protein kinases. Bioorg Med Chem Lett. 1999 May 17;9(10):1447-52.
• [47] CK2alpha and CK2alpha' subunits differ in their sensitivity to 4,5,6,7-tetrabromo- and 4,5,6,7-tetraiodo-1H-benzimidazole derivatives. Eur J Med Chem. 2012 Jan;47(1):345-50.
• [48] Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
• [49] The identification of potent and selective imidazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett. 2006 Jan 15;16(2):378-81.
• [50] DOI: 10.1158/1538-7445.AM2015-4693
• [51] Clinical pipeline report, company report or official report of HaiHe Biopharma.
• [52] Clinical pipeline report, company report or official report of Astex Pharmaceuticals.
• [53] WO patent application no. 2013,1850,32, Nanotherapeutics for drug targeting.
• [54] ERK Mutations Confer Resistance to Mitogen-Activated Protein Kinase Pathway Inhibitors
• [55] National Cancer Institute Drug Dictionary (drug name JSI1187).
• [56] 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.
• [57] 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.
• [58] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [59] Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Invest New Drugs. 2014 Apr;32(2):213-26.
• [60] Characterization of an inhibitory dynamic pharmacophore for the ERCC1-XPA interaction using a combined molecular dynamics and virtual screening app... J Mol Graph Model. 2009 Sep;28(2):113-30.
• [61] Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening. Mol Cancer Ther. 2011 Apr;10(4):591-602.
• [62] A phase Ib study of oral Chk1 inhibitor LY2880070 in combination with gemcitabine in patients with advanced or metastatic cancer. Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 3581-3581.
• [63] National Cancer Institute Drug Dictionary (drug id 730054).
• [64] Quantitative assessment of BCL-2:BIM complexes as a pharmacodynamic marker for venetoclax (ABT-199).
• [65] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [66] Chk1 Inhibitor MK-8776 Restores the Sensitivity of Chemotherapeutics in P-glycoprotein Overexpressing Cancer Cells. Int J Mol Sci. 2019 Aug 22;20(17):4095.
• [67] 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: 8040).
• [68] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [69] 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.
• [70] 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.
• [71] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [72] 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).
• [73] CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008.
• [74] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [75] Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015).Expert Opin Ther Pat. 2017 Jun;27(6):657-666.
• [76] 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.
• [77] Evidence for irreversible inhibition of glycogen synthase kinase-3beta by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904.
• [78] 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.
• [79] Company report (Neurim Pharmaceuticals)
• [80] 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.
• [81] 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.
• [82] Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models. Eur J Med Chem. 2009 Jun;44(6):2361-71.
• [83] Agents in development for the treatment of diabetic nephropathy. Expert Opin Emerg Drugs. 2008 Sep;13(3):447-63.
• [84] 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.
• [85] Array BioPharmas ARRY-797 Meets Primary Endpoint in Clinical Proof of Concept Trial in Osteoarthritis Patients Whose Pain is Poorly Controlled by NSAIDs
• [86] KC706, an Oral p38 MAP Kinase Inhibitor, Increases HDL-C. Circulation. 2007;116:II_126.
• [87] 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.
• [88] Novel pharmacotherapy: NNI-362, an allosteric p70S6 kinase stimulator, reverses cognitive and neural regenerative deficits in models of aging and disease. Stem Cell Res Ther. 2021 Jan 13;12(1):59.
• [89] 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.
• [90] Ribosomal S6 kinase (RSK) modulators: a patent review.Expert Opin Ther Pat. 2016 Sep;26(9):1061-78.
• [91] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [92] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [93] 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.
• [94] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [95] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [96] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [97] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [98] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.