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

General Information of Drug (ID: DM3WDZ5)

• Drug Name: MK-1775 Drug Info
• Synonyms: MK-1775; 955365-80-7; Adavosertib; MK1775; MK 1775; UNII-K2T6HJX3I3; AZD 1775; AZD-1775; AZD1775; 2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-(4-(4-methylpiperazin-1-yl)phenylamino)-1H-pyrazolo[3,4-d]pyrimidin-3(2H)-one; K2T6HJX3I3; 1-[6-(2-hydroxypropan-2-yl)pyridin-2-yl]-6-[4-(4-methylpiperazin-1-yl)anilino]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one; 2-Allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[3,4-d]pyrimidin-3(2H)-one; AK-99219

Indication

Disease Entry	ICD 11	Status	REF
Ovarian cancer	2C73	Phase 2	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]

• Cross-matching ID:
  PubChem CID: 24856436
  ChEBI ID: CHEBI:91414
  CAS Number: CAS 955365-80-7
  TTD Drug ID: DM3WDZ5

Molecule-Related Drug Atlas

Drug(s) Targeting Wee1-like protein kinase (WEE1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ZN-c3	DM4MSLY	Uterine serous carcinoma	2C72.1	Phase 2	[5]
9-hydroxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione	DMGCX7E	Discovery agent	N.A.	Investigative	[6]

Drug(s) Affected By Cyclin-dependent kinase 1 (CDK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[7]
Mechlorethamine	DM0CVXA	Chronic myelogenous leukaemia	2A20.0	Approved	[8]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[9]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[10]
Selenium	DM25CGV	N. A.	N. A.	Approved	[11]
Etretinate	DM2CZFA	Keratosis	ED56	Approved	[12]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[13]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[14]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[15]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[16]

Drug(s) Affected By Cellular tumor antigen p53 (TP53)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[17]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[18]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[19]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[21]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[22]
Floxuridine	DM04LR2	Colorectal cancer	2B91.Z	Approved	[23]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[24]
Mechlorethamine	DM0CVXA	Chronic myelogenous leukaemia	2A20.0	Approved	[25]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[26]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Wee1-like protein kinase (WEE1)	TTJFOAL	WEE1_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Drug Response	[4]
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Post-Translational Modifications	[4]
Wee1-like protein kinase	OTOHEU0N	WEE1_HUMAN	Post-Translational Modifications	[4]

References

• [1] 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. (Ligand id: 7702).
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.
• [4] Functional kinomics identifies candidate therapeutic targets in head and neck cancer. Clin Cancer Res. 2014 Aug 15;20(16):4274-88. doi: 10.1158/1078-0432.CCR-13-2858.
• [5] Clinical pipeline report, company report or official report of Zentalis Pharmaceuticals.
• [6] Receptor-based 3D-QSAR studies of checkpoint Wee1 kinase inhibitors. Eur J Med Chem. 2009 Apr;44(4):1383-95.
• [7] Cannabidiol-induced transcriptomic changes and cellular senescence in human Sertoli cells. Toxicol Sci. 2023 Feb 17;191(2):227-238. doi: 10.1093/toxsci/kfac131.
• [8] G2 delay induced by nitrogen mustard in human cells affects cyclin A/cdk2 and cyclin B1/cdc2-kinase complexes differently. J Biol Chem. 1993 Apr 15;268(11):8298-308.
• [9] mTOR inhibition reverses acquired endocrine therapy resistance of breast cancer cells at the cell proliferation and gene-expression levels. Cancer Sci. 2008 Oct;99(10):1992-2003. doi: 10.1111/j.1349-7006.2008.00955.x.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] Selenite and selenomethionine promote HL-60 cell cycle progression. J Nutr. 2002 Apr;132(4):674-9. doi: 10.1093/jn/132.4.674.
• [12] Bexarotene activates the p53/p73 pathway in human cutaneous T-cell lymphoma. Br J Dermatol. 2009 Mar;160(3):519-26. doi: 10.1111/j.1365-2133.2008.08931.x. Epub 2008 Nov 25.
• [13] Differential gene expression of sulindac-treated human breast epithelial cells. Int J Oncol. 2005 Dec;27(6):1727-36.
• [14] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [15] Simvastatin inactivates beta1-integrin and extracellular signal-related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cells. Cancer Sci. 2007 Jun;98(6):890-9.
• [16] Inhibition of prostate cancer cell colony formation by the flavonoid quercetin correlates with modulation of specific regulatory genes. Clin Diagn Lab Immunol. 2004 Jan;11(1):63-9. doi: 10.1128/cdli.11.1.63-69.2004.
• [17] p53-R175H mutant gains new function in regulation of doxorubicin-induced apoptosis. Int J Cancer. 2005 Apr 10;114(3):331-6. doi: 10.1002/ijc.20818.
• [18] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [19] Azidothymidine and cisplatin increase p14ARF expression in OVCAR-3 ovarian cancer cell line. Toxicol Appl Pharmacol. 2006 Oct 1;216(1):89-97. doi: 10.1016/j.taap.2006.04.015. Epub 2006 May 19.
• [20] Quantitative analysis of gene expression changes in response to genotoxic compounds. Toxicol In Vitro. 2017 Mar;39:15-28. doi: 10.1016/j.tiv.2016.11.004. Epub 2016 Nov 5.
• [21] Induction of apoptosis by cidofovir in human papillomavirus (HPV)-positive cells. Oncol Res. 2000;12(9-10):397-408. doi: 10.3727/096504001108747855.
• [22] Gallic acid potentiates the apoptotic effect of paclitaxel and carboplatin via overexpression of Bax and P53 on the MCF-7 human breast cancer cell line. J Biochem Mol Toxicol. 2021 Feb;35(2):e22638. doi: 10.1002/jbt.22638. Epub 2020 Oct 1.
• [23] Regulation of human dUTPase gene expression and p53-mediated transcriptional repression in response to oxaliplatin-induced DNA damage. Nucleic Acids Res. 2009 Jan;37(1):78-95. doi: 10.1093/nar/gkn910. Epub 2008 Nov 16.
• [24] Role of miRNA in the regulation of cannabidiol-mediated apoptosis in neuroblastoma cells. Oncotarget. 2019 Jan 1;10(1):45-59. doi: 10.18632/oncotarget.26534. eCollection 2019 Jan 1.
• [25] Nitrogen Mustard Alkylates and Cross-Links p53 in Human Keratinocytes. Chem Res Toxicol. 2022 Apr 18;35(4):636-650. doi: 10.1021/acs.chemrestox.1c00420. Epub 2022 Mar 21.
• [26] Fulvestrant induces resistance by modulating GPER and CDK6 expression: implication of methyltransferases, deacetylases and the hSWI/SNF chromatin remodelling complex. Br J Cancer. 2013 Nov 12;109(10):2751-62. doi: 10.1038/bjc.2013.583. Epub 2013 Oct 29.