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

General Information of Drug (ID: DM51B74)

• Drug Name: L-779450 Drug Info
• Synonyms: 303727-31-3; L-779450; L-779,450; 2-chloro-5-(2-phenyl-5-(pyridin-4-yl)-1H-imidazol-4-yl)phenol; L779450; CHEMBL373011; 2-chloro-5-(2-phenyl-5-pyridin-4-yl-1H-imidazol-4-yl)phenol; 2-(Phenyl)-4-(3-hydroxy-4-chlorophenyl)-5-(4-pyridyl)-1H-imidazole; 2-Chloro-5-[2-phenyl-5-(4-pyridinyl)-1H-imidazol-4-yl]phenol; C20H14ClN3O; L 779450; 2-chloro-5-[2-phenyl-5-(pyridin-4-yl)-1H-imidazol-4-yl]phenol; 2-chloro-5-[2-phenyl-4-(pyridin-4-yl)-1H-imidazol-5-yl]phenol; 2-chloro-5-(2-phenyl-4-(pyridin-4-yl)-1H-imidazol-5-yl)phenol

Indication

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

• Cross-matching ID:
  PubChem CID: 9950176
  ChEBI ID: CHEBI:93773
  CAS Number: CAS 303727-31-3
  TTD Drug ID: DM51B74

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	[2]
VX-680	DM93YKJ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[2]
JNJ-26483327	DMSQ3AZ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]
ISIS-CRP	DMQDUG4	Cardiovascular disease	BA00-BE2Z	Phase 1	[4]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[5]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[5]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[6]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[5]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[7]
BMS-536924	DMXJB4N	Discovery agent	N.A.	Investigative	[8]

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	[9]
SB 235699	DMNH8XU	Psoriasis vulgaris	EA90	Discontinued in Phase 1	[9]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[5]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[5]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[6]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[5]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[5]
Ro31-8220	DMDJLF0	Discovery agent	N.A.	Investigative	[5]
STAUROSPORINONE	DMU2H4K	Discovery agent	N.A.	Investigative	[5]
KT-5720	DM9J50F	Discovery agent	N.A.	Investigative	[5]

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	[10]
Losmapimod	DMIL37Z	Acute coronary syndrome	BA41	Phase 3	[10]
VX-702	DMKJDR6	Coronary artery disease	BA80	Phase 2a	[11]
VX-745	DMJAEG6	Alzheimer disease	8A20	Phase 2	[9]
Dilmapimod	DMBYJ92	Acute lung injury	NB32.3	Phase 2	[10]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[12]
PMID25991433-Compound-F2	DM37VIQ	N. A.	N. A.	Patented	[12]
PMID25991433-Compound-L2	DM58UO9	N. A.	N. A.	Patented	[12]
PMID25991433-Compound-L3	DM3LWUR	N. A.	N. A.	Patented	[12]
PMID25991433-Compound-L1	DM2135Y	N. A.	N. A.	Patented	[12]

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	[13]
LY2090314	DMTBFE4	Acute myeloid leukaemia	2A60	Phase 2	[14]
Lithium	DMZ3OU6	Fragile X syndrome	LD55	Phase 2	[15]
Tideglusib	DME4LA1	Osteosarcoma	2B51	Phase 2	[16]
9-ING-41	DM57TY3	Myelofibrosis	2A20.2	Phase 2	[17]
Neu-120	DMXKOUC	Parkinson disease	8A00.0	Phase 1/2	[18]
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[19]
CHIR-99021	DMB8MNU	Allergic inflammation	4A80-4A85	Patented	[20]
TDZD-8	DMG6Q45	Malignant glioma	2A00.0	Patented	[21]
AR-A014418	DMUPN01	Ovarian cancer	2C73	Patented	[22]

Drug(s) Targeting B-Raf messenger RNA (BRAF mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MLN2480	DMBR8NF	Solid tumour/cancer	2A00-2F9Z	Phase 2	[23]
RG7304	DMGFAVQ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[24]
SPN-803	DM8O2AQ	Parkinson disease	8A00.0	Phase 1	[23]
PLX-4720	DMBK9AM	Cutaneous melanoma	2C30	Phase 1	[25]
ZM-336372	DMD5JYQ	Discovery agent	N.A.	Investigative	[4]
PLX-ORI3	DMZG1L5	Solid tumour/cancer	2A00-2F9Z	Investigative	[23]
2-(Phenylamino)-6-(3-acetamidophenyl)pyrazine	DMPUARE	Discovery agent	N.A.	Investigative	[26]
ISIS 13741	DMC7Q38	Discovery agent	N.A.	Investigative	[27]
ISIS 14144	DMWIKD5	Discovery agent	N.A.	Investigative	[27]
PMID26061392C2	DMHZOIU	Discovery agent	N.A.	Investigative	[28]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
B-Raf messenger RNA (BRAF mRNA)	TT0EOB8	BRAF_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]
Stress-activated protein kinase 2a (p38 alpha)	TTQBR95	MK14_HUMAN	Inhibitor	[1]
Stress-activated protein kinase 2b (p38 beta)	TT73U6C	MK11_HUMAN	Inhibitor	[1]

References

• [1] The identification of potent and selective imidazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett. 2006 Jan 15;16(2):378-81.
• [2] 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.
• [3] National Cancer Institute Drug Dictionary (drug id 596693).
• [4] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
• [5] Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
• [6] Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
• [7] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [8] 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.
• [9] Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
• [10] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [11] 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.
• [12] c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
• [13] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [14] Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015).Expert Opin Ther Pat. 2017 Jun;27(6):657-666.
• [15] 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.
• [16] Evidence for irreversible inhibition of glycogen synthase kinase-3beta by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904.
• [17] 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.
• [18] Company report (Neurim Pharmaceuticals)
• [19] 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.
• [20] 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.
• [21] 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.
• [22] Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models. Eur J Med Chem. 2009 Jun;44(6):2361-71.
• [23] 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: 1943).
• [24] Clinical pipeline report, company report or official report of Roche.
• [25] Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol. 2011 Oct 30;29(11):1046-51.
• [26] Novel inhibitors of B-RAF based on a disubstituted pyrazine scaffold. Generation of a nanomolar lead. J Med Chem. 2006 Jan 12;49(1):407-16.
• [27] US patent application no. 5,981,731, Antisense oligonucleotide modulation of B-raf gene expression.
• [28] Photoactivatable Prodrugs of Antimelanoma Agent Vemurafenib. ACS Chem Biol. 2015 Sep 18;10(9):2099-107.