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

General Information of Drug (ID: DMX0TAM)

• Drug Name: NSC-95397 Drug Info
• Synonyms: NSC 95397; 93718-83-3; 2,3-Bis(2-hydroxyethylthio)-1,4-naphthalenedione; NSC95397; NSC-95397; 2,3-bis(2-hydroxyethylsulfanyl)naphthalene-1,4-dione; MLS002153403; CHEMBL429095; SMR001230781; SR-01000075930; 1,4-Naphthalenedione, 2,3-bis[(2-hydroxyethyl)thio]-; Tocris-1547; AC1Q6JAF; Lopac-N-1786; Lopac0_000629; KBioGR_000495; BSPBio_001155; KBioSS_000495; SCHEMBL2530685; AC1L66Q4; cid_262093; KBio3_000910; KBio2_005631; KBio2_003063; CHEBI:93193; KBio3_000909; KBio2_000495; CTK3I8111; DTXSID10294236; MolPort-003-958-936; HMS3268C19

Indication

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

• Cross-matching ID:
  PubChem CID: 262093
  ChEBI ID: CHEBI:93193
  CAS Number: CAS 93718-83-3
  TTD Drug ID: DMX0TAM

Molecule-Related Drug Atlas

Drug(s) Targeting M-phase inducer phosphatase 1 (MPIP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MX-7065	DMP26BW	Solid tumour/cancer	2A00-2F9Z	Terminated	[4]
Ro 20-1724	DM0PSCF	Asthma	CA23	Terminated	[5]
3-isopropyl-4-(phenylthio)naphthalene-1,2-dione	DMJZEMB	Discovery agent	N.A.	Investigative	[6]
4-(p-toluidino)-3-isopropylnaphthalene-1,2-dione	DMQA0EJ	Discovery agent	N.A.	Investigative	[6]
1-dodecyl-1H-indole-2,3-dione	DMK6BWV	Discovery agent	N.A.	Investigative	[7]
3-isopropyl-4-phenylnaphthalene-1,2-dione	DMYZCWX	Discovery agent	N.A.	Investigative	[6]
3-isopropyl-4-(phenylamino)naphthalene-1,2-dione	DMHAJ6W	Discovery agent	N.A.	Investigative	[6]
3-isopropylnaphthalene-1,2-dione	DM46ID2	Discovery agent	N.A.	Investigative	[6]
2-(1-dodecyl-1H-indol-3-yl)acetic acid	DMF2XHZ	Discovery agent	N.A.	Investigative	[7]
(E)-2-(1-decyl-2-oxoindolin-3-ylidene)acetic acid	DMI146O	Discovery agent	N.A.	Investigative	[7]

Drug(s) Targeting M-phase inducer phosphatase 2 (MPIP2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Avastin+/-Tarceva	DMA86FL	Non-small-cell lung cancer	2C25.Y	Phase 3	[8]
MX-7065	DMP26BW	Solid tumour/cancer	2A00-2F9Z	Terminated	[4]
2-Sulfhydryl-Ethanol	DMJBO3D	Discovery agent	N.A.	Investigative	[9]
Double Oxidized Cysteine	DM6TU84	Discovery agent	N.A.	Investigative	[9]
Cysteinesulfonic Acid	DMXI8FP	Discovery agent	N.A.	Investigative	[9]
Cysteine Sulfenic Acid	DM4GZUJ	N. A.	N. A.	Investigative	[10]
3-isopropyl-4-(phenylthio)naphthalene-1,2-dione	DMJZEMB	Discovery agent	N.A.	Investigative	[6]
4-(p-toluidino)-3-isopropylnaphthalene-1,2-dione	DMQA0EJ	Discovery agent	N.A.	Investigative	[6]
ADOCIAQUINONE B	DMPOU86	Discovery agent	N.A.	Investigative	[1]
3-isopropyl-4-phenylnaphthalene-1,2-dione	DMYZCWX	Discovery agent	N.A.	Investigative	[6]

Drug(s) Affected By Caspase-3 (CASP3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sevoflurane	DMC9O43	Anaesthesia	9A78.6	Approved	[11]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[12]
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[13]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[14]
Docetaxel	DMDI269	Advanced cancer	2A00-2F9Z	Approved	[15]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[16]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[17]
Mannitol	DMSCDY9	Bronchiectasis	CA24	Approved	[18]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[19]
Aprepitant	DM053KT	Depression	6A70-6A7Z	Approved	[20]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
M-phase inducer phosphatase 1 (MPIP1)	TTLZS4Q	MPIP1_HUMAN	Inhibitor	[2]
M-phase inducer phosphatase 2 (MPIP2)	TTR0SWN	MPIP2_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[3]

References

• [1] Novel naphthoquinone and quinolinedione inhibitors of CDC25 phosphatase activity with antiproliferative properties. Bioorg Med Chem. 2008 Oct 1;16(19):9040-9.
• [2] Structure-based de novo design and biochemical evaluation of novel Cdc25 phosphatase inhibitors. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4330-4.
• [3] The cytotoxic agents NSC-95397, brefeldin A, bortezomib and sanguinarine induce apoptosis in neuroendocrine tumors in vitro. Anticancer Res. 2010 Jan;30(1):149-56.
• [4] Handbook of Assay Development in Drug Discovery, Lisa K. Minor, 2013. Page(11).
• [5] Role of the Cdc25A phosphatase in human breast cancer. J Clin Invest. 2000 Sep;106(6):753-61.
• [6] Synthesis of miltirone analogues as inhibitors of Cdc25 phosphatases. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1905-8.
• [7] Design and synthesis of N-alkyl oxindolylidene acetic acids as a new class of potent Cdc25A inhibitors. Bioorg Med Chem Lett. 2008 Jun 1;18(11):3350-3.
• [8] Bioactivities of simplified adociaquinone B and naphthoquinone derivatives against Cdc25B, MKP-1, and MKP-3 phosphatases. Bioorg Med Chem. 2009 Mar 15;17(6):2276-81.
• [9] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [10] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
• [11] Different apoptosis ratios and gene expressions in two human cell lines after sevoflurane anaesthesia. Acta Anaesthesiol Scand. 2009 Oct;53(9):1192-9. doi: 10.1111/j.1399-6576.2009.02036.x. Epub 2009 Jun 30.
• [12] [Mechanisms underlying the effect of arsenic trioxide on proliferation inhibition and apoptosis induction in myeloma cell line u266]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007 Oct;15(5):982-5.
• [13] Lovastatin lactone elicits human lung cancer cell apoptosis via a COX-2/PPAR-dependent pathway. Oncotarget. 2016 Mar 1;7(9):10345-62. doi: 10.18632/oncotarget.7213.
• [14] Induction of apoptosis by cidofovir in human papillomavirus (HPV)-positive cells. Oncol Res. 2000;12(9-10):397-408. doi: 10.3727/096504001108747855.
• [15] Comparison of burst of reactive oxygen species and activation of caspase-3 in apoptosis of K562 and HL-60 cells induced by docetaxel. Cancer Lett. 2004 Oct 8;214(1):103-13. doi: 10.1016/j.canlet.2004.03.047.
• [16] Induction of mitochondrial manganese superoxide dismutase confers resistance to apoptosis in acute myeloblastic leukaemia cells exposed to etoposide. Br J Haematol. 2000 Mar;108(3):574-81. doi: 10.1046/j.1365-2141.2000.01852.x.
• [17] Cisplatin-enhanced sensitivity of glioblastoma multiforme U251 cells to adenovirus-delivered TRAIL in vitro. Tumour Biol. 2010 Dec;31(6):613-22. doi: 10.1007/s13277-010-0077-x. Epub 2010 Jul 11.
• [18] Insulin-like growth factor I is the key growth factor in serum that protects neuroblastoma cells from hyperosmotic-induced apoptosis. J Cell Physiol. 2000 Jan;182(1):24-32. doi: 10.1002/(SICI)1097-4652(200001)182:1<24::AID-JCP3>3.0.CO;2-6.
• [19] mRNA expression analysis of a variety of apoptosis-related genes, including the novel gene of the BCL2-family, BCL2L12, in HL-60 leukemia cells after treatment with carboplatin and doxorubicin. Biol Chem. 2004 Nov;385(11):1099-103. doi: 10.1515/BC.2004.143.
• [20] Neurokinin-1 receptor (NK1R) inhibition sensitizes APL cells to anti-tumor effect of arsenic trioxide via restriction of NF-B axis: Shedding new light on resistance to Aprepitant. Int J Biochem Cell Biol. 2018 Oct;103:105-114. doi: 10.1016/j.biocel.2018.08.010. Epub 2018 Aug 23.