Details of the Drug

General Information of Drug (ID: )

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 3	[1]

• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw)
  Logarithm of the Partition Coefficient (xlogp)
  Rotatable Bond Count (rotbonds)
  Hydrogen Bond Donor Count (hbonddonor)
  Hydrogen Bond Acceptor Count (hbondacc)

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Erbb2 tyrosine kinase receptor (HER2)	TT6EO5L	ERBB2_HUMAN	Not Available	[2]
Farnesoid X-activated receptor (FXR)	TTS4UGC	NR1H4_HUMAN	Antagonist	[3]
Vascular endothelial growth factor A (VEGFA)	TTOHSBA	VEGFA_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1)	OTG2T749	CP24A_HUMAN	Gene/Protein Processing	[4]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Gene/Protein Processing	[5]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Protein Interaction/Cellular Processes	[6]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Gene/Protein Processing	[7]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Gene/Protein Processing	[7]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Gene/Protein Processing	[7]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Protein Interaction/Cellular Processes	[8]
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Gene/Protein Processing	[9]
ATP-binding cassette sub-family C member 3 (ABCC3)	OTC3IJV4	MRP3_HUMAN	Gene/Protein Processing	[10]
ATP-binding cassette sub-family G member 5 (ABCG5)	OT1OMY93	ABCG5_HUMAN	Gene/Protein Processing	[11]

Molecular Expression Atlas of This Drug

• The Studied Disease: Breast cancer
• ICD Disease Classification: 2C60-2C65

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Vascular endothelial growth factor A (VEGFA)	DTT	VEGFA	3.61E-01	0.15	0.47

References

• [1] AVEREL: a randomized phase III Trial evaluating bevacizumab in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer. J Clin Oncol. 2013 May 10;31(14):1719-25.
• [2] Clinical pipeline report, company report or official report of Roche (2009).
• [3] Lithocholic acid decreases expression of bile salt export pump through farnesoid X receptor antagonist activity. J Biol Chem. 2002 Aug 30;277(35):31441-7.
• [4] The aryl hydrocarbon receptor activator benzo[a]pyrene enhances vitamin D3 catabolism in macrophages. Toxicol Sci. 2009 May;109(1):50-8.
• [5] A novel sialyltransferase inhibitor suppresses FAK/paxillin signaling and cancer angiogenesis and metastasis pathways. Cancer Res. 2011 Jan 15;71(2):473-83. doi: 10.1158/0008-5472.CAN-10-1303. Epub 2011 Jan 11.
• [6] Biochemical, pharmaceutical and therapeutic properties of long-acting lithocholic acid derivatized exendin-4 analogs. J Control Release. 2010 Mar 3;142(2):206-13. doi: 10.1016/j.jconrel.2009.10.025. Epub 2009 Nov 10.
• [7] Selective and potent inhibitors of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) that metabolizes neurosteroids derived from progesterone. Chem Biol Interact. 2003 Feb 1;143-144:503-13.
• [8] Sex steroid receptors, secondary bile acids and colorectal cancer. A possible mechanism of interaction. Panminerva Med. 2003 Dec;45(4):261-6.
• [9] The role of lithocholic acid in the regulation of bile acid detoxication, synthesis, and transport proteins in rat and human intestine and liver slices. Toxicol In Vitro. 2011 Feb;25(1):80-90.
• [10] Induction of ABCC3 (MRP3) by pregnane X receptor activators. Drug Metab Dispos. 2003 Nov;31(11):1296-9. doi: 10.1124/dmd.31.11.1296.
• [11] Potency of individual bile acids to regulate bile acid synthesis and transport genes in primary human hepatocyte cultures. Toxicol Sci. 2014 Oct;141(2):538-46. doi: 10.1093/toxsci/kfu151. Epub 2014 Jul 23.