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

General Information of Drug (ID: DMHK0F6)

• Drug Name: NSC-106970 Drug Info
• Synonyms: 33429-83-3; Quercetin 3,4'-dimethyl ether; 5,7-Dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-3-methoxy-4H-chromen-4-one; QUERCETIN-3,4'-DIMETHYL ETHER; NSC-106970; 5,7,3'-Trihydroxy-3,4'-dimethoxyflavone; CHEBI:70008; 3,4'-dimethoxy-5,7,3'-trihydroxyflavone; 5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-3-methoxychromen-4-one; 5,7-Dihydroxy-2-(3-hydroxy-4-methoxy-phenyl)-3-methoxy-chromen-4-one; 4H-1-Benzopyran-4-one, 5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-3-methoxy-; NSC106970; 3-O-Methyltamarixetin; AC1NTGVE

Indication

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

• Cross-matching ID:
  PubChem CID: 5380905
  ChEBI ID: CHEMBL309263
  CAS Number: CAS 33429-83-3
  TTD Drug ID: DMHK0F6

Molecule-Related Drug Atlas

Drug(s) Targeting Tubulin (TUB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Docetaxel	DMDI269	Advanced cancer	2A00-2F9Z	Approved	[3]
Vinorelbine	DMVXFYE	Advanced cancer	2A00-2F9Z	Approved	[4]
Cabazitaxel	DMPAZHC	Breast cancer	2C60-2C65	Approved	[5]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[6]
Ixabepilone	DM2OZ3G	Breast cancer	2C60-2C65	Approved	[5]
Eribulin	DM1DX4Q	Breast cancer	2C60-2C65	Approved	[5]
Epothilon	DMITJRU	Ovarian cancer	2C73	Phase 3	[7]
DOLASTATIN-10	DMDUV1S	Solid tumour/cancer	2A00-2F9Z	Phase 2	[8]
BMS-188797	DML1CK2	Solid tumour/cancer	2A00-2F9Z	Phase 2	[9]
Indibulin	DM6OFJ8	Advanced sarcoma	2A60-2C35	Phase 2	[10]

Drug(s) Targeting Tubulin beta (TUBB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Vincristine	DMINOX3	Acute lymphoblastic leukaemia	2A85	Approved	[11]
Albendazole	DMYZ57N	Echinococcus granulosus infectious disease		Approved	[12]
Vindesine	DMVR628	Acute lymphoblastic leukaemia	2A85	Approved	[13]
Taxol	DMUOT9V	Breast cancer	2C60-2C65	Approved	[14]
Mebendazole	DMO14SG	Ascariasis	1F62	Approved	[12]
Plinabulin	DMD7L48	Non-small-cell lung cancer	2C25.Y	Phase 3	[15]
Batabulin	DMHWE5R	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[16]
ABT-751	DMNG35S	Solid tumour/cancer	2A00-2F9Z	Phase 2	[17]
DOLASTATIN-10	DMDUV1S	Solid tumour/cancer	2A00-2F9Z	Phase 2	[18]
BNC-105	DMJC8DR	Mesothelioma	2C51.2	Phase 2	[19]

Drug(s) Affected By M-phase inducer phosphatase 3 (CDC25C)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[20]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[21]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[22]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[23]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[24]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[25]
Acetic Acid, Glacial	DM4SJ5Y	infection in the ear canal	AA0Y	Approved	[26]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[27]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[28]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[29]

Drug(s) Affected By Cyclin-dependent kinase inhibitor 1 (CDKN1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[30]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[31]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[32]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[33]
Talazoparib	DM1KS78	Breast cancer	2C60-2C65	Approved	[34]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[35]
Etretinate	DM2CZFA	Keratosis	ED56	Approved	[36]
Prednisone	DM2HG4X	Acute asthma	CA23	Approved	[37]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[38]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[39]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Inhibitor	[1]
Tubulin beta (TUBB)	TTYFKSZ	NOUNIPROTAC	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Gene/Protein Processing	[2]
M-phase inducer phosphatase 3 (CDC25C)	OTPQI71S	MPIP3_HUMAN	Post-Translational Modifications	[2]

References

• [1] Structure-activity requirements for flavone cytotoxicity and binding to tubulin. J Med Chem. 1998 Jun 18;41(13):2333-8.
• [2] 5,7,3'-Trihydroxy-3,4'-dimethoxyflavone inhibits the tubulin polymerization and activates the sphingomyelin pathway. Mol Carcinog. 2011 Feb;50(2):113-22. doi: 10.1002/mc.20693. Epub 2010 Dec 10.
• [3] Docetaxel: a review of its use in metastatic breast cancer. Drugs. 2005;65(17):2513-31.
• [4] Vinca alkaloid and MDR1. Gan To Kagaku Ryoho. 2008 Jul;35(7):1086-9.
• [5] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [6] Vitamin K3 disrupts the microtubule networks by binding to tubulin: a novel mechanism of its antiproliferative activity. Biochemistry. 2009 Jul 28;48(29):6963-74.
• [7] Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.
• [8] Synthesis and biological activity of chimeric structures derived from the cytotoxic natural compounds dolastatin 10 and dolastatin 15. J Med Chem. 1998 Apr 23;41(9):1524-30.
• [9] Phase I and pharmacokinetic study of BMS-188797, a new taxane analog, administered on a weekly schedule in patients with advanced malignancies. Clin Cancer Res. 2003 Nov 1;9(14):5187-94.
• [10] 2011 Pipeline of ZioPharm.
• [11] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [12] Flubendazole interferes with a wide spectrum of cell homeostatic mechanisms in Echinococcus granulosus protoscoleces. Parasitol Int. 2009 Sep;58(3):270-7.
• [13] Antiproliferating activity of the mitotic inhibitor pironetin against vindesine- and paclitaxel-resistant human small cell lung cancer H69 cells. Anticancer Res. 2007 Mar-Apr;27(2):729-36.
• [14] Paclitaxel directly binds to Bcl-2 and functionally mimics activity of Nur77. Cancer Res. 2009 Sep 1;69(17):6906-14.
• [15] NPI-2358 is a tubulin-depolymerizing agent: in-vitro evidence for activity as a tumor vascular-disrupting agent. Anticancer Drugs. 2006 Jan;17(1):25-31.
• [16] Hydrophilic, pro-drug analogues of T138067 are efficacious in controlling tumor growth in vivo and show a decreased ability to cross the blood brain barrier. J Med Chem. 2001 Oct 25;44(22):3599-605.
• [17] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [18] Total synthesis and biological evaluation of ustiloxin natural products and two analogs. Bioorg Med Chem Lett. 2006 Sep 15;16(18):4804-7.
• [19] The vascular disrupting agent BNC105 potentiates the efficacy of VEGF and mTOR inhibitors in renal and breast cancer.Cancer Biol Ther.2014;15(11):1552-60.
• [20] 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.
• [21] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [22] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [23] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [24] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [25] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [26] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [27] Arsenic trioxide-mediated growth inhibition in MC/CAR myeloma cells via cell cycle arrest in association with induction of cyclin-dependent kinase inhibitor, p21, and apoptosis. Cancer Res. 2000 Jun 1;60(11):3065-71.
• [28] Delta9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Cancer Res. 2006 Jul 1;66(13):6615-21. doi: 10.1158/0008-5472.CAN-05-4566.
• [29] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [30] Zidovudine induces S-phase arrest and cell cycle gene expression changes in human cells. Mutagenesis. 2005 Mar;20(2):139-46. doi: 10.1093/mutage/gei019. Epub 2005 Mar 22.
• [31] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [32] Gene expression profiles with activation of the estrogen receptor alpha-selective estrogen receptor modulator complex in breast cancer cells expressing wild-type estrogen receptor. Cancer Res. 2002 Aug 1;62(15):4419-26.
• [33] Leptomycin B reduces primary and acquired resistance of gefitinib in lung cancer cells. Toxicol Appl Pharmacol. 2017 Nov 15;335:16-27. doi: 10.1016/j.taap.2017.09.017. Epub 2017 Sep 21.
• [34] BMN 673 (talazoparib): A potent PARP inhibitor for triple negative breast cancer with different genetic profile. J Biochem Mol Toxicol. 2019 May;33(5):e22286. doi: 10.1002/jbt.22286. Epub 2019 Jan 23.
• [35] Gene expression after treatment with hydrogen peroxide, menadione, or t-butyl hydroperoxide in breast cancer cells. Cancer Res. 2002 Nov 1;62(21):6246-54.
• [36] 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.
• [37] Glucocorticoids induce G1 arrest of lymphoblastic cells through retinoblastoma protein Rb1 dephosphorylation in childhood acute lymphoblastic leukemia in vivo. Cancer Biol Ther. 2004 May;3(5):470-6. doi: 10.4161/cbt.3.5.838. Epub 2004 May 9.
• [38] Ciprofloxacin mediated cell growth inhibition, S/G2-M cell cycle arrest, and apoptosis in a human transitional cell carcinoma of the bladder cell line. Clin Cancer Res. 2000 Mar;6(3):891-900.
• [39] Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.