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

General Information of Drug (ID: DMHTG38)

• Drug Name: XL844 Drug Info
• Synonyms: SCHEMBL14517914; XL-844

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[1]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 10016910
  TTD Drug ID: DMHTG38

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]
PMID22564207C25b	DMBMYKQ	Discovery agent	N.A.	Investigative	[5]
DEBROMOHYMENIALDISINE	DMDLER8	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 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	[14]
LY2880070	DMADEHZ	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[15]
RG7741	DMK6P9J	Lymphoma	2A80-2A86	Phase 1	[16]
GDC-0425	DMDZ26X	Lymphoma	2A80-2A86	Phase 1	[17]
AZD7762	DM1FW0C	Solid tumour/cancer	2A00-2F9Z	Phase 1	[18]
MK-8776	DMAS1RB	Hodgkin lymphoma	2B30	Phase 1	[19]
Diamidothiazole derivative 1	DM02V5Q	N. A.	N. A.	Patented	[20]

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	Modulator	[2]
Serine/threonine-protein kinase Chk2 (RAD53)	TT9ABMF	CHK2_HUMAN	Modulator	[2]

References

• [1] ClinicalTrials.gov (NCT00234481) Safety Study of XL844 in Subjects With Chronic Lymphocytic Leukemia. U.S. National Institutes of Health.
• [2] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [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] Discovery of an orally efficacious inhibitor of anaplastic lymphoma kinase. J Med Chem. 2012 May 24;55(10):4580-93.
• [6] Potent inhibition of checkpoint kinase activity by a hymenialdisine-derived indoloazepine. Bioorg Med Chem Lett. 2004 Aug 16;14(16):4319-21.
• [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] 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] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [15] 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.
• [16] National Cancer Institute Drug Dictionary (drug id 730054).
• [17] Quantitative assessment of BCL-2:BIM complexes as a pharmacodynamic marker for venetoclax (ABT-199).
• [18] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [19] 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.
• [20] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.