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

General Information of Drug (ID: DM5LUED)

• Drug Name: 3-keto-lithocholic acid Drug Info
• Synonyms: dehydrolithocholic acid; 3-keto-LCA

Indication

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

• Cross-matching ID:
  PubChem CID: 5283906
  ChEBI ID: CHEMBL410893
  CAS Number: CAS 1553-56-6
  TTD Drug ID: DM5LUED

Molecule-Related Drug Atlas

Drug(s) Targeting Vitamin D3 receptor (VDR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ergocalciferol	DMHO0AR	Hypoparathyroidism	5A50	Approved	[5]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[6]
Calcidiol	DMN4CV5	Hypophosphatemia		Approved	[5]
Doxercalciferol	DM6FG1P	Chronic kidney disease	GB61	Approved	[7]
Calcipotriol	DM03CP7	Psoriasis	EA90	Approved	[8]
Falecalcitrol	DMBI9ZJ	Hyperparathyroidism	5A51	Approved	[9]
Dihydrotachysterol	DMFB97P	Hypocalcemia	5B5K.1	Approved	[10]
Cholecalciferol	DMGU74E	Adult acute monocytic leukemia		Approved	[11]
Paricalcitol	DMYBV3G	Hyperparathyroidism	5A51	Approved	[12]
Seocalcitol	DMKL9QO	Rickets	5B57	Phase 3	[13]

Drug(s) Targeting Pregnane X receptor (NR1I2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
WAY-214950	DM8ODI7	Discovery agent	N.A.	Investigative	[14]
Hyperforin	DM2L3PE	Discovery agent	N.A.	Investigative	[15]
pregnenolone-16alpha-carbonitrile	DM0LW7G	Discovery agent	N.A.	Investigative	[16]
trihydroxycholestane	DMSP56N	Discovery agent	N.A.	Investigative	[17]
schisandrin A	DMWQ480	Discovery agent	N.A.	Investigative	[18]

Drug(s) Affected By Dehydrogenase/reductase SDR family member 11 (DHRS11)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[4]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[4]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[19]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[20]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[21]
Flufenamic Acid	DMC8VNH	Dysmenorrhea	GA34.3	Approved	[4]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[22]
Demecolcine	DMCZQGK	Solid tumour/cancer	2A00-2F9Z	Approved	[23]
Zoledronate	DMIXC7G	Adenocarcinoma	2D40	Approved	[24]
Temozolomide	DMKECZD	Adenocarcinoma	2D40	Approved	[25]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Pregnane X receptor (NR1I2)	TT7LCTF	NR1I2_HUMAN	Agonist	[2]
Vitamin D3 receptor (VDR)	TTK59TV	VDR_HUMAN	Agonist	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Dehydrogenase/reductase SDR family member 11 (DHRS11)	OTU3J0ZL	DHR11_HUMAN	Biotransformations	[4]

References

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• [2] The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3369-74.
• [3] Vitamin D receptor as an intestinal bile acid sensor. Science. 2002 May 17;296(5571):1313-6.
• [4] 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.
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• [8] Cellular and molecular mechanisms involved in the action of vitamin D analogs targeting vitiligo depigmentation. Curr Drug Targets. 2008 Apr;9(4):345-59.
• [9] Synthesis and biological evaluations of A-ring isomers of 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3. Bioorg Med Chem. 2000 Aug;8(8):2157-66.
• [10] In vivo metabolism of the vitamin D analog, dihydrotachysterol. Evidence for formation of 1 alpha,25- and 1 beta,25-dihydroxy-dihydrotachysterol metabolites and studies of their biological activity. J Biol Chem. 1993 Jan 5;268(1):282-92.
• [11] [Vitamin D2 or vitamin D3]. Rev Med Interne. 2008 Oct;29(10):815-20.
• [12] New acquisitions in therapy of secondary hyperparathyroidism in chronic kidney disease and peritoneal dialysis patients: role of vitamin D receptor... Contrib Nephrol. 2009;163:219-226.
• [13] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [14] Indazole-based liver X receptor (LXR) modulators with maintained atherosclerotic lesion reduction activity but diminished stimulation of hepatic tr... J Med Chem. 2008 Nov 27;51(22):7161-8.
• [15] Pregnane X receptor (PXR) regulates P-glycoprotein at the blood-brain barrier: functional similarities between pig and human PXR. J Pharmacol Exp Ther. 2009 Apr;329(1):141-9.
• [16] An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell. 1998 Jan 9;92(1):73-82.
• [17] Identification of bile acid precursors as endogenous ligands for the nuclear xenobiotic pregnane X receptor. Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):223-8.
• [18] Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and inc... J Pharmacol Exp Ther. 2006 Mar;316(3):1369-77.
• [19] 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.
• [20] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [21] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [22] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [23] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [24] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [25] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.