Details of the Drug Combination

General Information of Drug Combination (ID: DC68VCS)

• Drug Combination Name: Raloxifene + Dorsomorphin
• Indication: Diffuse intrinsic pontine glioma; Status: Investigative [1]
• Component Drugs:
  Raloxifene (DMDKF3M): Small molecular drug
  Dorsomorphin (DMKYXJW): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SU-DIPG-XIII
  Zero Interaction Potency (ZIP) Score: 10.774
  Bliss Independence Score: 14.304
  Loewe Additivity Score: 7.575
  LHighest Single Agent (HSA) Score: 9.163

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Raloxifene

Disease Entry	ICD 11	Status	REF
Osteoporosis	FB83.0	Approved	[2]

Raloxifene Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Modulator	[4]

Raloxifene Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[5]

Raloxifene Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[6]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[7]
UDP-glucuronosyltransferase 1A10 (UGT1A10)	DEL5N6Y	UD110_HUMAN	Metabolism	[8]

Indication(s) of Dorsomorphin

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[3]

Dorsomorphin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
AMP-activated protein kinase (AMPK)	TTLAFZV	AAPK1_HUMAN; AAKB1_HUMAN; AAKG1_HUMAN	Inhibitor	[10]

Dorsomorphin Interacts with 39 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cyclic AMP-responsive element-binding protein 1 (CREB1)	OT1MDLA1	CREB1_HUMAN	Increases Phosphorylation	[11]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[11]
Forkhead box protein O1 (FOXO1)	OTPJRB6D	FOXO1_HUMAN	Decreases Expression	[12]
Bone morphogenetic protein receptor type-1B (BMPR1B)	OTGFN0OD	BMR1B_HUMAN	Increases Expression	[13]
Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)	OTVT4YA1	ATG7_HUMAN	Increases Expression	[14]
Serine/threonine-protein kinase Chk2 (CHEK2)	OT8ZPCNS	CHK2_HUMAN	Increases Phosphorylation	[15]
Transferrin receptor protein 1 (TFRC)	OT8ZPBDL	TFR1_HUMAN	Decreases Expression	[13]
Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1)	OTM0GDTP	IF2A_HUMAN	Increases Phosphorylation	[16]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[15]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[14]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Decreases Expression	[15]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[15]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[14]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[14]
Bone morphogenetic protein receptor type-1A (BMPR1A)	OTQOA4ZH	BMR1A_HUMAN	Decreases Expression	[13]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[15]
Serine/threonine-protein kinase mTOR (MTOR)	OTHH8KU7	MTOR_HUMAN	Increases Phosphorylation	[14]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Cleavage	[15]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[14]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Increases Phosphorylation	[14]
Hepcidin (HAMP)	OT607RBL	HEPC_HUMAN	Decreases Expression	[13]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[15]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[14]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[14]
Acetyl-CoA carboxylase 1 (ACACA)	OT5CQPZY	ACACA_HUMAN	Decreases Expression	[17]
5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)	OT7TNF0L	AAPK1_HUMAN	Decreases Expression	[14]
Serine-protein kinase ATM (ATM)	OTQVOHLT	ATM_HUMAN	Increases Phosphorylation	[15]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Decreases Expression	[14]
Beclin-1 (BECN1)	OT4X293M	BECN1_HUMAN	Decreases Expression	[18]
Endoplasmic reticulum membrane sensor NFE2L1 (NFE2L1)	OT1QHOS2	NF2L1_HUMAN	Decreases Expression	[17]
Methylcytosine dioxygenase TET2 (TET2)	OTKKT03T	TET2_HUMAN	Decreases Expression	[14]
Hemojuvelin (HJV)	OT4235J2	RGMC_HUMAN	Decreases Expression	[13]
NAD-dependent protein deacetylase sirtuin-1 (SIRT1)	OTAYZMOY	SIR1_HUMAN	Decreases Expression	[19]
Forkhead box protein P3 (FOXP3)	OTA9Z9OC	FOXP3_HUMAN	Decreases Expression	[14]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Decreases Lipidation	[18]
Transcription factor SOX-17 (SOX17)	OT9H4WWE	SOX17_HUMAN	Decreases Localization	[20]
Transferrin receptor protein 2 (TFR2)	OTMYCCEO	TFR2_HUMAN	Decreases Expression	[13]
Krueppel-like factor 2 (KLF2)	OTIP1UFX	KLF2_HUMAN	Decreases Expression	[21]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Response To Substance	[15]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Primitive neuroectodermal tumor	DCA8TST	TC-32	Investigative	[1]

References

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• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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• [4] 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. (Target id: 620).
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