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

General Information of Drug (ID: DM2BKU8)

• Drug Name: K00244 Drug Info
• Synonyms: GSK-3 Inhibitor XIII; N-(5-methyl-1H-pyrazol-3-yl)-2-phenylquinazolin-4-amine; GSK3-XIII; K00244; 404828-08-6; CHEMBL359482; (5-Methyl-1H-pyrazol-3-yl)-(2-phenylquinazolin-4-yl)amine; CHEBI:78544; AC1O4WD1; SCHEMBL462877; GTPL5976; CTK4I3154; HMS3229I06; BDBM228657; BCP12434; BDBM50162083; ZINC16052235; IN1311; AKOS025394676; DB08454; CCG-101293; NCGC00387776-01; ACM404828086; RT-013126; N-(3-methyl-1H-pyrazol-5-yl)-2-phenylquinazolin-4-amine; (5-Methyl-1H-pyrazol-3-yl)-(2-phenyl-quinazolin-4-yl)-amine

Indication

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

• Cross-matching ID:
  PubChem CID: 6419766
  ChEBI ID: CHEBI:78544
  TTD Drug ID: DM2BKU8

Molecule-Related Drug Atlas

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	[2]
LY2090314	DMTBFE4	Acute myeloid leukaemia	2A60	Phase 2	[3]
Lithium	DMZ3OU6	Bipolar disorder	6A60	Phase 2	[4]
Tideglusib	DME4LA1	Alzheimer disease	8A20	Phase 2	[5]
9-ING-41	DM57TY3	Myelofibrosis	2A20.2	Phase 2	[6]
Neu-120	DMXKOUC	Parkinson disease	8A00.0	Phase 1/2	[7]
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[8]
CHIR-99021	DMB8MNU	Allergic inflammation	4A80-4A85	Patented	[9]
TDZD-8	DMG6Q45	Malignant glioma	2A00.0	Patented	[10]
AR-A014418	DMUPN01	Ovarian cancer	2C73	Patented	[11]

Drug(s) Targeting Proto-oncogene c-Src (SRC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[12]
Bosutinib	DMTI8YE	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[12]
SKI-758	DMQ8E9R	Ischemia	8B10-8B11	Approved	[13]
Herbimycin A	DM6YWBF	Solid tumour/cancer	2A00-2F9Z	Approved	[14]
AL3818	DM3WP0N	Alveolar soft part sarcoma	2A60-2C35	Phase 3	[15]
CP-868596	DMZIM37	Gastrointestinal cancer	2C11	Phase 3	[15]
Masitinib	DMRSNEU	Amyotrophic lateral sclerosis	8B60.0	Phase 3	[16]
KX-01	DMF0NA9	Actinic keratosis	EK90.0	Phase 3	[17]
Saracatinib	DMBLHGP	Hematologic tumour	2B33.Y	Phase 2	[18]
TPX-0046	DMIVE67	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[19]

Drug(s) Targeting Aurora kinase C (AURKC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PHA-739358	DMGYBZI	Prostate cancer	2C82.0	Phase 2	[20]
ABT-348	DMMZOYN	Haematological malignancy	2B33.Y	Phase 2	[21]
HPP-607	DM5VSZR	Solid tumour/cancer	2A00-2F9Z	Phase 1	[22]
AMG 900	DMASGXJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[23]
SNS-314	DMAC5F2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[24]
GSK1070916	DMXRPT6	Advanced solid tumour	2A00-2F9Z	Phase 1	[25]
GSK1070916A	DMCJUI9	Solid tumour/cancer	2A00-2F9Z	Phase 1	[25]
MK-6592	DMB5NOI	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[26]
Indirubin-3'-monoxime	DMLRQH0	Discovery agent	N.A.	Investigative	[27]
SU 6656	DMF1P6W	Discovery agent	N.A.	Investigative	[28]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Aurora kinase C (AURKC)	TTLYXIT	AURKC_HUMAN	Inhibitor	[1]
Glycogen synthase kinase-3 beta (GSK-3B)	TTRSMW9	GSK3B_HUMAN	Inhibitor	[1]
Proto-oncogene c-Src (SRC)	TT6PKBN	SRC_HUMAN	Inhibitor	[1]

References

• [1] The discovery of the potent aurora inhibitor MK-0457 (VX-680). Bioorg Med Chem Lett. 2009 Jul 1;19(13):3586-92.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015).Expert Opin Ther Pat. 2017 Jun;27(6):657-666.
• [4] 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.
• [5] Evidence for irreversible inhibition of glycogen synthase kinase-3beta by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904.
• [6] 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.
• [7] Company report (Neurim Pharmaceuticals)
• [8] 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.
• [9] 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.
• [10] 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.
• [11] Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models. Eur J Med Chem. 2009 Jun;44(6):2361-71.
• [12] 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.
• [13] Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles. J Med Chem. 2006 Dec 28;49(26):7868-76.
• [14] In vivo antitumor activity of herbimycin A, a tyrosine kinase inhibitor, targeted against BCR/ABL oncoprotein in mice bearing BCR/ABL-transfected cells. Leuk Res. 1994 Nov;18(11):867-73.
• [15] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [16] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [17] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [18] Novel dual Src/Abl inhibitors for hematologic and solid malignancies.Expert Opin Investig Drugs.2010 Aug;19(8):931-45.
• [19] Clinical pipeline report, company report or official report of Turning Point Therapeutics.
• [20] Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition. J Med Chem. 2005 Apr 21;48(8):3080-4.
• [21] Preclinical characterization of ABT-348, a kinase inhibitor targeting the aurora, vascular endothelial growth factor receptor/platelet-derived growth factor receptor, and Src kinase families. J Pharmacol Exp Ther. 2012 Dec;343(3):617-27.
• [22] 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: 1936).
• [23] Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. Cancer Res. 2010 Dec 1;70(23):9846-54.
• [24] SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2010 Mar;65(4):707-17.
• [25] Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase. J Med Chem. 2010 May 27;53(10):3973-4001.
• [26] Clinical experience with aurora kinase inhibitors: a review. Oncologist. 2009 Aug;14(8):780-93.
• [27] An integrated computational approach to the phenomenon of potent and selective inhibition of aurora kinases B and C by a series of 7-substituted in... J Med Chem. 2007 Aug 23;50(17):4027-37.
• [28] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.