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

General Information of Drug (ID: DMDLER8)

• Drug Name: DEBROMOHYMENIALDISINE Drug Info

Indication

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

• Cross-matching ID:
  PubChem CID: 135451156
  CAS Number: CAS 125118-55-0
  TTD Drug ID: DMDLER8

Molecule-Related Drug Atlas

Drug(s) Targeting Serine/threonine-protein kinase Chk2 (RAD53)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
E7850	DM8K5IF	Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]
PMID27410995-Compound-Figure3j	DMJRZLB	N. A.	N. A.	Patented	[4]
XL844	DMHTG38	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[5]
PMID22564207C25b	DMBMYKQ	Discovery agent	N.A.	Investigative	[6]
2-(4-Phenoxy-phenyl)-1H-benzoimidazol-5-ylamine	DMSPOAT	Discovery agent	N.A.	Investigative	[7]
PV-1019	DMRI1LF	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
5-Nitro-2-(4-phenoxy-phenyl)-1H-benzoimidazole	DM26MIC	Discovery agent	N.A.	Investigative	[7]
CCT-241533	DMZXFT9	Solid tumour/cancer	2A00-2F9Z	Investigative	[9]
Chk2 inhibitor II	DMNSPFG	Discovery agent	N.A.	Investigative	[10]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Selumetinib	DMC7W6R	Melanoma	2C30	Phase 3	[11]
Diamidothiazole derivative 1	DM02V5Q	N. A.	N. A.	Patented	[12]
Pyridic ketone derivative 1	DM3GU7K	N. A.	N. A.	Patented	[13]
RDEA-436	DM0ILRU	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[14]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[15]
REVERSINE	DMWDNOK	Discovery agent	N.A.	Investigative	[16]
OROIDIN	DMA2DQT	Discovery agent	N.A.	Investigative	[2]
PD98059	DMZC90M	Cardiac arrest	MC82	Investigative	[17]
4,5-Dibromo-1H-pyrrole-2-carboxylic acid amide	DMDM9UV	Discovery agent	N.A.	Investigative	[2]
5-phenylamino-4-cyano-3-hydroxy-isothiazole	DMX6R0H	Discovery agent	N.A.	Investigative	[18]

Drug(s) Targeting Raf messenger RNA (Raf mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MLN2480	DMBR8NF	Solid tumour/cancer	2A00-2F9Z	Phase 2	[19]
RG7304	DMGFAVQ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[20]
SPN-803	DM8O2AQ	Parkinson disease	8A00.0	Phase 1	[19]
LXH254	DMQE9PS	Non-small-cell lung cancer	2C25.Y	Phase 1	[11]
ICo-007	DM79W8K	Diabetic macular edema	9B71.02	Phase 1	[21]
LErafAON	DMNHPOT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[22]
ZM-336372	DMD5JYQ	Discovery agent	N.A.	Investigative	[23]
6-[(E)-2-(4-Fluoro-phenyl)-vinyl]-9H-purine	DMDNG8F	Discovery agent	N.A.	Investigative	[24]
PLX-ORI3	DMZG1L5	Solid tumour/cancer	2A00-2F9Z	Investigative	[19]
6-Benzylsulfanyl-9H-purine	DMI7FNZ	Discovery agent	N.A.	Investigative	[24]

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	[25]
HH2710	DM0C5MV	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[26]
ASTX029	DMVZXIA	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[27]
VAN-10-4-eluting stent	DM3ZW6A	Artery stenosis	BD52	Phase 1	[28]
GDC-0994	DMFC2OY	Solid tumour/cancer	2A00-2F9Z	Phase 1	[29]
JSI-1187	DMVJWBS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[30]
LY3214996	DMFDAY7	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
CHIR-99021	DMB8MNU	Allergic inflammation	4A80-4A85	Patented	[31]
COR-D	DMLXMCB	T-cell leukaemia	2A90	Preclinical	[32]
SB220025	DMSBUET	Arthritis	FA20	Terminated	[33]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LY2603618	DMCXRZF	Pancreatic cancer	2C10	Phase 2	[34]
UCN-01	DMUNJZB	Non-small-cell lung cancer	2C25.Y	Phase 2	[35]
SCH-900776	DM67EMK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[36]
LY2606368	DM4XMF7	Ovarian cancer	2C73	Phase 2	[11]
LY2880070	DMADEHZ	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[37]
RG7741	DMK6P9J	Lymphoma	2A80-2A86	Phase 1	[38]
GDC-0425	DMDZ26X	Lymphoma	2A80-2A86	Phase 1	[39]
AZD7762	DM1FW0C	Solid tumour/cancer	2A00-2F9Z	Phase 1	[40]
MK-8776	DMAS1RB	Hodgkin lymphoma	2B30	Phase 1	[41]
Diamidothiazole derivative 1	DM02V5Q	N. A.	N. A.	Patented	[12]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Checkpoint kinase-1 (CHK1)	TTTU902	CHK1_HUMAN	Inhibitor	[1]
ERK activator kinase 1 (MEK1)	TTIDAPM	MP2K1_HUMAN	Inhibitor	[2]
Extracellular signal-regulated kinase 2 (ERK2)	TT4TQBX	MK01_HUMAN	Inhibitor	[1]
Raf messenger RNA (Raf mRNA)	TTAN5W2	RAF1_HUMAN	Inhibitor	[2]
Serine/threonine-protein kinase Chk2 (RAD53)	TT9ABMF	CHK2_HUMAN	Inhibitor	[1]

References

• [1] Potent inhibition of checkpoint kinase activity by a hymenialdisine-derived indoloazepine. Bioorg Med Chem Lett. 2004 Aug 16;14(16):4319-21.
• [2] 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.
• [3] 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: 1988).
• [4] Ribosomal S6 kinase (RSK) modulators: a patent review.Expert Opin Ther Pat. 2016 Sep;26(9):1061-78.
• [5] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [6] Discovery of an orally efficacious inhibitor of anaplastic lymphoma kinase. J Med Chem. 2012 May 24;55(10):4580-93.
• [7] Checkpoint kinase inhibitors: SAR and radioprotective properties of a series of 2-arylbenzimidazoles. J Med Chem. 2005 Mar 24;48(6):1873-85.
• [8] Cellular inhibition of checkpoint kinase 2 (Chk2) and potentiation of camptothecins and radiation by the novel Chk2 inhibitor PV1019 [7-nitro-1H-indole-2-carboxylic acid {4-[1-(guanidinohydrazone)-ethyl]-phenyl}-amide]. J Pharmacol Exp Ther. 2009 Dec;331(3):816-26.
• [9] CCT241533 Is a Potent and Selective Inhibitor of CHK2 that Potentiates the Cytotoxicity of PARP Inhibitors. Cancer Res. 2011 Jan 15;71(2):463-72.
• [10] A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8.
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
• [13] MEK inhibitors in oncology: a patent review (2015-Present).Expert Opin Ther Pat. 2017 Aug;27(8):887-906.
• [14] Clinical pipeline report, company report or official report of MedKoo Biosciences.
• [15] Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
• [16] Reversine increases the plasticity of lineage-committed mammalian cells. Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10482-7.
• [17] The MEK1 inhibitor PD98059 sensitizes C8161 melanoma cells to cisplatin-induced apoptosis. Melanoma Res. 2001 Feb;11(1):11-9.
• [18] Discovery of 3-hydroxy-4-carboxyalkylamidino-5-arylamino-isothiazoles as potent MEK1 inhibitors. Bioorg Med Chem Lett. 2006 Aug 1;16(15):3975-80.
• [19] 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: 2184).
• [20] Clinical pipeline report, company report or official report of Roche.
• [21] Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2009).
• [22] Combination with liposome-entrapped, ends-modified raf antisense oligonucleotide (LErafAON) improves the anti-tumor efficacies of cisplatin, epirubicin, mitoxantrone, docetaxel and gemcitabine. Anticancer Drugs. 2004 Mar;15(3):243-53.
• [23] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
• [24] Synthesis and biological testing of purine derivatives as potential ATP-competitive kinase inhibitors. J Med Chem. 2005 Feb 10;48(3):710-22.
• [25] DOI: 10.1158/1538-7445.AM2015-4693
• [26] Clinical pipeline report, company report or official report of HaiHe Biopharma.
• [27] Clinical pipeline report, company report or official report of Astex Pharmaceuticals.
• [28] WO patent application no. 2013,1850,32, Nanotherapeutics for drug targeting.
• [29] ERK Mutations Confer Resistance to Mitogen-Activated Protein Kinase Pathway Inhibitors
• [30] National Cancer Institute Drug Dictionary (drug name JSI1187).
• [31] 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.
• [32] 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.
• [33] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [34] Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Invest New Drugs. 2014 Apr;32(2):213-26.
• [35] 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.
• [36] 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.
• [37] 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.
• [38] National Cancer Institute Drug Dictionary (drug id 730054).
• [39] Quantitative assessment of BCL-2:BIM complexes as a pharmacodynamic marker for venetoclax (ABT-199).
• [40] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [41] 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.