Details of the Drug Combination

General Information of Drug Combination (ID: DCA7Y10)

• Drug Combination Name: Flavonoid derivative 1 + Acarbose
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Flavonoid derivative 1 (DMCQP0B): Small molecular drug
  Acarbose (DMRM3AW): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 6.3
  Bliss Independence Score: 6.3
  Loewe Additivity Score: 20.79
  LHighest Single Agent (HSA) Score: 20.79

Molecular Interaction Atlas of This Drug Combination

Flavonoid derivative 1 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Signal transducer and activator of transcription 3 (STAT3)	TTH8FZW	STAT3_HUMAN	Inhibitor	[9]

Flavonoid derivative 1 Interacts with 38 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Decreases Activity	[10]
Tumor protein p73 (TP73)	OT0LUO47	P73_HUMAN	Increases Expression	[11]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B)	OTL9I7LO	GA45B_HUMAN	Increases Expression	[11]
CCN family member 5 (CCN5)	OTADU8JJ	CCN5_HUMAN	Decreases Expression	[7]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Decreases Activity	[12]
Interstitial collagenase (MMP1)	OTI4I2V1	MMP1_HUMAN	Decreases Expression	[13]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[6]
HLA class II histocompatibility antigen gamma chain (CD74)	OTO16X4Q	HG2A_HUMAN	Decreases Expression	[14]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Expression	[15]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[16]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Increases Expression	[17]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[18]
Transcription factor JunB (JUNB)	OTG2JXV5	JUNB_HUMAN	Decreases Activity	[12]
Transcription factor JunD (JUND)	OTNKACJD	JUND_HUMAN	Decreases Activity	[12]
Cadherin-2 (CDH2)	OTH0Y56P	CADH2_HUMAN	Decreases Expression	[17]
Nuclear receptor subfamily 1 group D member 1 (NR1D1)	OTJ38PTB	NR1D1_HUMAN	Decreases Expression	[7]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[19]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[19]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Increases Expression	[11]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Decreases Expression	[6]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[7]
Cyclin-dependent kinase 4 inhibitor C (CDKN2C)	OTCLOV90	CDN2C_HUMAN	Decreases Expression	[11]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Increases Phosphorylation	[20]
Mitogen-activated protein kinase 9 (MAPK9)	OTCEVJ9E	MK09_HUMAN	Increases Phosphorylation	[20]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[21]
Serine/threonine-protein kinase PLK1 (PLK1)	OTRZX45T	PLK1_HUMAN	Decreases Expression	[22]
Protein FosB (FOSB)	OTW6C05J	FOSB_HUMAN	Decreases Activity	[12]
Mitogen-activated protein kinase 10 (MAPK10)	OTC46VX1	MK10_HUMAN	Increases Phosphorylation	[20]
Sestrin-2 (SESN2)	OT889IXY	SESN2_HUMAN	Increases Expression	[23]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[20]
Solute carrier family 22 member 6 (SLC22A6)	OTKRCBVM	S22A6_HUMAN	Decreases Activity	[24]
Quinone oxidoreductase PIG3 (TP53I3)	OTSCM68G	QORX_HUMAN	Increases Expression	[11]
Dehydrogenase/reductase SDR family member 11 (DHRS11)	OTU3J0ZL	DHR11_HUMAN	Decreases Activity	[25]
Organic anion transporter 3 (SLC22A8)	OT8BY933	S22A8_HUMAN	Decreases Activity	[24]
Autophagy protein 5 (ATG5)	OT4T5SMS	ATG5_HUMAN	Increases Expression	[6]
Tumor protein 63 (TP63)	OT0WOOKQ	P63_HUMAN	Increases Expression	[11]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Affects Activity	[26]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1)	OTNEN8QK	SO1B1_HUMAN	Decreases Activity	[27]

Indication(s) of Acarbose

Disease Entry	ICD 11	Status	REF
Diabetic complication	5A2Y	Approved	[2]
Non-insulin dependent diabetes	5A11	Approved	[3]
Cardiovascular disease	BA00-BE2Z	Phase 3	[2]

Acarbose Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Intestinal maltase-glucoamylase (MGAM)	TTXWASR	MGA_HUMAN	Modulator	[28]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [2] 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: 6791).
• [3] Acarbose FDA Label
• [4] Inhibition of cell growth and VEGF expression in ovarian cancer cells by flavonoids. Nutr Cancer. 2008;60(6):800-9.
• [5] Structure-dependent modulation of aryl hydrocarbon receptor-mediated activities by flavonoids. Toxicol Sci. 2018 Jul 1;164(1):205-217.
• [6] Antitumor activity of luteolin in human colon cancer SW620 cells is mediated by the ERK/FOXO3a signaling pathway. Toxicol In Vitro. 2020 Aug;66:104852. doi: 10.1016/j.tiv.2020.104852. Epub 2020 Apr 5.
• [7] Cytotoxicity of flavones and flavonols to a human esophageal squamous cell carcinoma cell line (KYSE-510) by induction of G2/M arrest and apoptosis. Toxicol In Vitro. 2009 Aug;23(5):797-807. doi: 10.1016/j.tiv.2009.04.007. Epub 2009 May 3.
• [8] Genetic variants of human UGT1A3: functional characterization and frequency distribution in a Chinese Han population. Drug Metab Dispos. 2006 Sep;34(9):1462-7. doi: 10.1124/dmd.106.009761. Epub 2006 May 31.
• [9] A STAT inhibitor patent review: progress since 2011.Expert Opin Ther Pat. 2015;25(12):1397-421.
• [10] Drug interaction study of flavonoids toward CYP3A4 and their quantitative structure activity relationship (QSAR) analysis for predicting potential effects. Toxicol Lett. 2018 Sep 15;294:27-36.
• [11] Flavones and flavonols exert cytotoxic effects on a human oesophageal adenocarcinoma cell line (OE33) by causing G2/M arrest and inducing apoptosis. Food Chem Toxicol. 2008 Jun;46(6):2042-53. doi: 10.1016/j.fct.2008.01.049. Epub 2008 Feb 7.
• [12] Luteolin, a flavonoid, inhibits AP-1 activation by basophils. Biochem Biophys Res Commun. 2006 Feb 3;340(1):1-7. doi: 10.1016/j.bbrc.2005.11.157. Epub 2005 Dec 6.
• [13] The flavonoids apigenin and luteolin suppress ultraviolet A-induced matrix metalloproteinase-1 expression via MAPKs and AP-1-dependent signaling in HaCaT cells. J Dermatol Sci. 2011 Jan;61(1):23-31. doi: 10.1016/j.jdermsci.2010.10.016. Epub 2010 Nov 9.
• [14] Suppressive Effects of Selected Food Phytochemicals on CD74 Expression in NCI-N87 Gastric Carcinoma Cells. J Clin Biochem Nutr. 2008 Sep;43(2):109-17. doi: 10.3164/jcbn.2008054.
• [15] Structure-activity relationship and mechanism of flavonoids on the inhibitory activity of P-glycoprotein (P-gp)-mediated transport of rhodamine123 and daunorubicin in P-gp overexpressed human mouth epidermal carcinoma (KB/MDR) cells. Food Chem Toxicol. 2021 Sep;155:112381. doi: 10.1016/j.fct.2021.112381. Epub 2021 Jul 1.
• [16] Blockade of the epidermal growth factor receptor tyrosine kinase activity by quercetin and luteolin leads to growth inhibition and apoptosis of pancreatic tumor cells. Anticancer Res. 2002 May-Jun;22(3):1615-27.
• [17] Luteolin exerts pro-apoptotic effect and anti-migration effects on A549 lung adenocarcinoma cells through the activation of MEK/ERK signaling pathway. Chem Biol Interact. 2016 Sep 25;257:26-34. doi: 10.1016/j.cbi.2016.07.028. Epub 2016 Jul 26.
• [18] The genotoxicity potential of luteolin is enhanced by CYP1A1 and CYP1A2 in human lymphoblastoid TK6 cells. Toxicol Lett. 2021 Jun 15;344:58-68. doi: 10.1016/j.toxlet.2021.03.006. Epub 2021 Mar 13.
• [19] Luteolin, quercetin and ursolic acid are potent inhibitors of proliferation and inducers of apoptosis in both KRAS and BRAF mutated human colorectal cancer cells. Cancer Lett. 2009 Aug 28;281(2):162-70. doi: 10.1016/j.canlet.2009.02.041. Epub 2009 Apr 2.
• [20] Luteolin induced G2 phase cell cycle arrest and apoptosis on non-small cell lung cancer cells. Toxicol In Vitro. 2011 Oct;25(7):1385-91. doi: 10.1016/j.tiv.2011.05.009. Epub 2011 May 13.
• [21] Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK1. Biochem Pharmacol. 2001 May 15;61(10):1205-15. doi: 10.1016/s0006-2952(01)00583-4.
• [22] Luteolin exerts anti-tumor activity through the suppression of epidermal growth factor receptor-mediated pathway in MDA-MB-231 ER-negative breast cancer cells. Food Chem Toxicol. 2012 Nov;50(11):4136-43. doi: 10.1016/j.fct.2012.08.025. Epub 2012 Aug 20.
• [23] Luteolin prevents liver from tunicamycin-induced endoplasmic reticulum stress via nuclear factor erythroid 2-related factor 2-dependent sestrin 2 induction. Toxicol Appl Pharmacol. 2020 Jul 15;399:115036. doi: 10.1016/j.taap.2020.115036. Epub 2020 May 11.
• [24] Potent Inhibitors of Organic Anion Transporters 1 and 3 From Natural Compounds and Their Protective Effect on Aristolochic Acid Nephropathy. Toxicol Sci. 2020 Jun 1;175(2):279-291. doi: 10.1093/toxsci/kfaa033.
• [25] Rabbit dehydrogenase/reductase SDR family member 11 (DHRS11): Its identity with acetohexamide reductase with broad substrate specificity and inhibitor sensitivity, different from human DHRS11. Chem Biol Interact. 2019 May 25;305:12-20. doi: 10.1016/j.cbi.2019.03.026. Epub 2019 Mar 26.
• [26] Luteolin enhances the bioavailability of benzo(a)pyrene in human colon carcinoma cells. Arch Biochem Biophys. 2010 Jun 15;498(2):111-8. doi: 10.1016/j.abb.2010.04.009. Epub 2010 Apr 18.
• [27] Drug interaction study of flavonoids toward OATP1B1 and their 3D structure activity relationship analysis for predicting hepatoprotective effects. Toxicology. 2020 May 15;437:152445. doi: 10.1016/j.tox.2020.152445. Epub 2020 Apr 4.
• [28] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.