Details of the Drug Combination

General Information of Drug Combination (ID: DC3BFP4)

• Drug Combination Name: MK-2206 + Mitotane
• Indication: Ewing sarcoma; Status: Investigative [1]
• Component Drugs:
  MK-2206 (DMT1OZ6): Small molecular drug
  Mitotane (DMU1GX0): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: TC-71
  Zero Interaction Potency (ZIP) Score: 2.174
  Bliss Independence Score: 3.029
  Loewe Additivity Score: 1.534
  LHighest Single Agent (HSA) Score: 4.272

Molecular Interaction Atlas of This Drug Combination

Indication(s) of MK-2206

Disease Entry	ICD 11	Status	REF
Rectal adenocarcinoma	2B92	Phase 2	[2]
Nasopharyngeal carcinoma	2B6B	Investigative	[3]

MK-2206 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
RAC-gamma serine/threonine-protein kinase (AKT3)	TTAZ05C	AKT3_HUMAN	Modulator	[6]
E2 ubiquitin-conjugating enzyme T (UBE2T)	TT0A1R8	UBE2T_HUMAN	Inhibitor	[3]

MK-2206 Interacts with 20 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Increases Expression	[7]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Secretion	[5]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Increases Expression	[7]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Secretion	[5]
Endothelin-1 (EDN1)	OTZCACEG	EDN1_HUMAN	Decreases Expression	[5]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Increases Expression	[8]
Vascular endothelial growth factor receptor 1 (FLT1)	OTT0OGYS	VGFR1_HUMAN	Decreases Expression	[5]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Increases Secretion	[5]
Endothelin receptor type B (EDNRB)	OTLLZV3P	EDNRB_HUMAN	Increases Expression	[5]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Affects Response To Substance	[9]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[10]
T-lymphocyte activation antigen CD80 (CD80)	OTJBLUQE	CD80_HUMAN	Decreases Expression	[5]
T-lymphocyte activation antigen CD86 (CD86)	OTJCSBPC	CD86_HUMAN	Decreases Expression	[5]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Cleavage	[10]
CCAAT/enhancer-binding protein alpha (CEBPA)	OTOM9OE4	CEBPA_HUMAN	Decreases Expression	[5]
Actin, aortic smooth muscle (ACTA2)	OTEDLG8E	ACTA_HUMAN	Decreases Expression	[11]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[10]
Interferon regulatory factor 8 (IRF8)	OT8YSNI4	IRF8_HUMAN	Decreases Expression	[5]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1)	OTHBQVD5	4EBP1_HUMAN	Decreases Phosphorylation	[10]
Proline-rich AKT1 substrate 1 (AKT1S1)	OT4JHN4Y	AKTS1_HUMAN	Decreases Phosphorylation	[12]

Indication(s) of Mitotane

Disease Entry	ICD 11	Status	REF
Adrenocortical carcinoma	2D11.Z	Approved	[4]

Mitotane Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Binder	[13]

Mitotane Interacts with 41 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 11B1, mitochondrial (CYP11B1)	OTKKL894	C11B1_HUMAN	Increases Expression	[14]
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 (HSD3B2)	OT02MSKN	3BHS2_HUMAN	Decreases Expression	[14]
Cholesterol side-chain cleavage enzyme, mitochondrial (CYP11A1)	OT2NV3AN	CP11A_HUMAN	Decreases Expression	[15]
Steroid 21-hydroxylase (CYP21A2)	OTN0UDVP	CP21A_HUMAN	Decreases Expression	[15]
Steroidogenic acute regulatory protein, mitochondrial (STAR)	OTFEZ5AI	STAR_HUMAN	Decreases Expression	[15]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[16]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[17]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Expression	[18]
Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1)	OTZKVLVJ	CP17A_HUMAN	Decreases Expression	[18]
cAMP-dependent protein kinase type I-alpha regulatory subunit (PRKAR1A)	OT589JA2	KAP0_HUMAN	Decreases Expression	[18]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[18]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[18]
Cytochrome c oxidase subunit 2 (COX2)	OTTMVBJJ	COX2_HUMAN	Decreases Expression	[19]
Cytochrome c oxidase subunit 4 isoform 1, mitochondrial (COX4I1)	OTU0FC24	COX41_HUMAN	Decreases Expression	[19]
Cytochrome P450 11B2, mitochondrial (CYP11B2)	OTIOLWYN	C11B2_HUMAN	Decreases Expression	[19]
Stearoyl-CoA desaturase (SCD)	OTB1073G	SCD_HUMAN	Decreases Expression	[20]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[20]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Increases Activity	[21]
Sex hormone-binding globulin (SHBG)	OTPWU5IW	SHBG_HUMAN	Increases Expression	[22]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Affects Binding	[23]
Glia-derived nexin (SERPINE2)	OTYF5340	GDN_HUMAN	Increases Expression	[24]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[20]
Corticosteroid-binding globulin (SERPINA6)	OTOIBEW7	CBG_HUMAN	Increases Expression	[22]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Affects Binding	[23]
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1)	OTNAZVKB	3BHS1_HUMAN	Decreases Expression	[24]
Cyclic AMP-responsive element-binding protein 1 (CREB1)	OT1MDLA1	CREB1_HUMAN	Increases Activity	[25]
ETS domain-containing protein Elk-1 (ELK1)	OTH9MXD6	ELK1_HUMAN	Increases Activity	[25]
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Increases Expression	[20]
Ribonucleoside-diphosphate reductase large subunit (RRM1)	OTXGQOR9	RIR1_HUMAN	Increases Expression	[26]
Phosphoenolpyruvate carboxykinase, cytosolic (PCK1)	OTNWEJ5Y	PCKGC_HUMAN	Decreases Expression	[20]
Glucose-6-phosphatase catalytic subunit 1 (G6PC1)	OTJ6FM9F	G6PC1_HUMAN	Decreases Expression	[20]
Neurogenic locus notch homolog protein 1 (NOTCH1)	OTI1WADQ	NOTC1_HUMAN	Increases Activity	[25]
Fatty acid synthase (FASN)	OTFII9KG	FAS_HUMAN	Decreases Expression	[20]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Increases Activity	[27]
Mitochondrial 10-formyltetrahydrofolate dehydrogenase (ALDH1L2)	OTCH86VF	AL1L2_HUMAN	Increases Expression	[24]
Estrogen receptor beta (ESR2)	OTXNR2WQ	ESR2_HUMAN	Increases Activity	[21]
Thyroid hormone-inducible hepatic protein (THRSP)	OTKYE01L	THRSP_HUMAN	Decreases Expression	[20]
CREB-binding protein (CREBBP)	OTPA4QGM	CBP_HUMAN	Increases Activity	[28]
Tribbles homolog 3 (TRIB3)	OTG5OS7X	TRIB3_HUMAN	Increases Expression	[24]
Growth/differentiation factor 15 (GDF15)	OTWQN50N	GDF15_HUMAN	Increases Expression	[24]
Interferon beta (IFNB1)	OTYQGUB5	IFNB_HUMAN	Increases Response To Substance	[29]

References

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