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

General Information of Drug (ID: DM02V5Q)

• Drug Name: Diamidothiazole derivative 1 Drug Info
• Synonyms: PMID26161698-Compound-53
• Cross-matching ID:
  PubChem CID: 25256147
  TTD Drug ID: DM02V5Q

Molecule-Related Drug Atlas

Drug(s) Targeting Aurora kinase (AURK)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AZD2811	DMYUNXP	Small-cell lung cancer	2C25.Y	Phase 2	[2]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Selumetinib	DMC7W6R	Melanoma	2C30	Phase 3	[3]
Pyridic ketone derivative 1	DM3GU7K	N. A.	N. A.	Patented	[4]
RDEA-436	DM0ILRU	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[5]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[6]
DEBROMOHYMENIALDISINE	DMDLER8	Discovery agent	N.A.	Investigative	[7]
REVERSINE	DMWDNOK	Discovery agent	N.A.	Investigative	[8]
OROIDIN	DMA2DQT	Discovery agent	N.A.	Investigative	[7]
PD98059	DMZC90M	Cardiac arrest	MC82	Investigative	[9]
4,5-Dibromo-1H-pyrrole-2-carboxylic acid amide	DMDM9UV	Discovery agent	N.A.	Investigative	[7]
5-phenylamino-4-cyano-3-hydroxy-isothiazole	DMX6R0H	Discovery agent	N.A.	Investigative	[10]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LY2603618	DMCXRZF	Pancreatic cancer	2C10	Phase 2	[11]
UCN-01	DMUNJZB	Non-small-cell lung cancer	2C25.Y	Phase 2	[12]
SCH-900776	DM67EMK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[13]
LY2606368	DM4XMF7	Ovarian cancer	2C73	Phase 2	[3]
LY2880070	DMADEHZ	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[14]
RG7741	DMK6P9J	Lymphoma	2A80-2A86	Phase 1	[15]
GDC-0425	DMDZ26X	Lymphoma	2A80-2A86	Phase 1	[16]
AZD7762	DM1FW0C	Solid tumour/cancer	2A00-2F9Z	Phase 1	[17]
MK-8776	DMAS1RB	Hodgkin lymphoma	2B30	Phase 1	[18]
XL844	DMHTG38	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[19]

Drug(s) Targeting Cyclin-dependent kinase 2 (CDK2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
R-roscovitine	DMSH108	Non-small-cell lung cancer	2C25.Y	Phase 2	[20]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[21]
PHA848125	DMS2Q9G	Thymic cancer	2C27	Phase 2	[22]
TG02	DMZFIGQ	Anaplastic astrocytoma	2A00.0	Phase 1/2	[23]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[24]
FN-1501	DM7BMD6	Solid tumour/cancer	2A00-2F9Z	Phase 1	[25]
AG-024322	DMY4WVK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[20]
PHA-793887	DM2Y4FG	Solid tumour/cancer	2A00-2F9Z	Phase 1	[26]
SNS-032	DMEITAS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[27]
CYC065	DM9ODT6	Lymphoma	2A80-2A86	Phase 1	[3]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Aurora kinase (AURK)	TTCY4SB	NOUNIPROTAC	Inhibitor	[1]
Checkpoint kinase-1 (CHK1)	TTTU902	CHK1_HUMAN	Inhibitor	[1]
Cyclin-dependent kinase 2 (CDK2)	TT7HF4W	CDK2_HUMAN	Inhibitor	[1]
ERK activator kinase 1 (MEK1)	TTIDAPM	MP2K1_HUMAN	Inhibitor	[1]

References

• [1] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
• [2] Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo. Sci Transl Med. 2016 Feb 10;8(325):325ra17.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] MEK inhibitors in oncology: a patent review (2015-Present).Expert Opin Ther Pat. 2017 Aug;27(8):887-906.
• [5] Clinical pipeline report, company report or official report of MedKoo Biosciences.
• [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] 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.
• [8] Reversine increases the plasticity of lineage-committed mammalian cells. Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10482-7.
• [9] The MEK1 inhibitor PD98059 sensitizes C8161 melanoma cells to cisplatin-induced apoptosis. Melanoma Res. 2001 Feb;11(1):11-9.
• [10] Discovery of 3-hydroxy-4-carboxyalkylamidino-5-arylamino-isothiazoles as potent MEK1 inhibitors. Bioorg Med Chem Lett. 2006 Aug 1;16(15):3975-80.
• [11] Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Invest New Drugs. 2014 Apr;32(2):213-26.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] National Cancer Institute Drug Dictionary (drug id 730054).
• [16] Quantitative assessment of BCL-2:BIM complexes as a pharmacodynamic marker for venetoclax (ABT-199).
• [17] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [18] 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.
• [19] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [20] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [21] 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.
• [22] Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor. J Med Chem. 2009 Aug 27;52(16):5152-63.
• [23] Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42.
• [24] Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia. 2013 Dec;27(12):2366-75.
• [25] Discovery of 4-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazole-3-carboxamide (FN-1501), an FLT3- and CDK-Kinase Inhibitor with Potentially High Efficiency against Acute Myelocytic Leukemia. J Med Chem. 2018 Feb 22;61(4):1499-1518.
• [26] A first in man, phase I dose-escalation study of PHA-793887, an inhibitor of multiple cyclin-dependent kinases (CDK2, 1 and 4) reveals unexpected h... Cell Cycle. 2011 Mar 15;10(6):963-70.
• [27] Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45.