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

General Information of Drug (ID: DMBI9ZJ)

• Drug Name: Falecalcitrol Drug Info
• Synonyms: Falecalcitriol; falecalcitriol; Flocalcitriol; 83805-11-2; calcitriol hexafluoride; Hornel, Fulstan; Falecalcitriol [INN]; ST-630; ST 630; Fulstan; Ro 23-4194; UNII-G70A8514T8; C27H38F6O3; Hornel; 26,26,26,27,27,27-Hexafluoro-1,25-dihydroxyvitamin D3; G70A8514T8; (1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-7a-methyl-1-[(2R)-7,7,7-trifluoro-6-hydroxy-6-(trifluoromethyl)heptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol; Hexafluorocalcitriol; 9,10-Secocholesta-5,7,10(19)-triene-1,3,25-triol,; Fulstan (TN); Horner (TN)

Indication

Disease Entry	ICD 11	Status	REF
Hyperparathyroidism	5A51	Approved	[1]

• Cross-matching ID:
  PubChem CID: 5282190
  CAS Number: CAS 83805-11-2
  TTD Drug ID: DMBI9ZJ

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	[4]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[5]
Calcidiol	DMN4CV5	Hypophosphatemia		Approved	[4]
Doxercalciferol	DM6FG1P	Chronic kidney disease	GB61	Approved	[6]
Calcipotriol	DM03CP7	Psoriasis	EA90	Approved	[7]
Dihydrotachysterol	DMFB97P	Hypocalcemia	5B5K.1	Approved	[8]
Cholecalciferol	DMGU74E	Adult acute monocytic leukemia		Approved	[9]
Paricalcitol	DMYBV3G	Hyperparathyroidism	5A51	Approved	[10]
Seocalcitol	DMKL9QO	Rickets	5B57	Phase 3	[11]
S-06911	DMAYTIH	Osteoporosis	FB83.0	Phase 3	[12]

Drug(s) Affected By Osteocalcin (BGLAP)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[13]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[14]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[15]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[16]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[17]
Glucosamine	DM4ZLFD	Osteoarthritis	FA00-FA05	Approved	[18]
Pamidronate	DMB4AVP	Bone Paget disease		Approved	[19]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[20]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[21]
Ifosfamide	DMCT3I8	Adult central nervous system germ cell tumor		Approved	[22]

Drug(s) Affected By Alkaline phosphatase, tissue-nonspecific isozyme (ALPL)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[23]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[24]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[25]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[15]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[26]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[27]
Procaine	DM4LSNE	Anaesthesia	9A78.6	Approved	[28]
Glucosamine	DM4ZLFD	Osteoarthritis	FA00-FA05	Approved	[18]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[3]
Aldosterone	DM9S2JW	Hypertension	BA00-BA04	Approved	[29]

Drug(s) Affected By Osteopontin (SPP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[25]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[30]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[31]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[32]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[33]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[34]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[35]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[36]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[37]
Isoniazid	DM5JVS3	Latent tuberculosis infection		Approved	[38]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Vitamin D3 receptor (VDR)	TTK59TV	VDR_HUMAN	Agonist	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL)	OTG7J4BP	PPBT_HUMAN	Gene/Protein Processing	[3]
Osteocalcin (BGLAP)	OTK1YLWQ	OSTCN_HUMAN	Gene/Protein Processing	[3]
Osteopontin (SPP1)	OTJGC23Y	OSTP_HUMAN	Gene/Protein Processing	[3]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] 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.
• [3] A highly potent 26,27-Hexafluoro-1a,25-dihydroxyvitamin D3 on calcification in SV40-transformed human fetal osteoblastic cells. Calcif Tissue Int. 2002 Jun;70(6):488-95.
• [4] Vitamin D in health and disease. Clin J Am Soc Nephrol. 2008 Sep;3(5):1535-41.
• [5] Kaposi sarcoma is a therapeutic target for vitamin D(3) receptor agonist. Blood. 2000 Nov 1;96(9):3188-94.
• [6] Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.
• [7] Cellular and molecular mechanisms involved in the action of vitamin D analogs targeting vitiligo depigmentation. Curr Drug Targets. 2008 Apr;9(4):345-59.
• [8] 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.
• [9] [Vitamin D2 or vitamin D3]. Rev Med Interne. 2008 Oct;29(10):815-20.
• [10] 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.
• [11] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [12] Evidence for tissue- and cell-type selective activation of the vitamin D receptor by Ro-26-9228, a noncalcemic analog of vitamin D3. J Cell Biochem. 2003 Feb 1;88(2):267-73.
• [13] 20-Cyclopropyl-cholecalciferol vitamin D3 analogs: a unique class of potent inhibitors of proliferation of human prostate, breast and myeloid leukemia cell lines. Anticancer Res. 1999 May-Jun;19(3A):1689-97.
• [14] Cannabidiol induces osteoblast differentiation via angiopoietin1 and p38 MAPK. Environ Toxicol. 2020 Dec;35(12):1318-1325. doi: 10.1002/tox.22996. Epub 2020 Jul 13.
• [15] Protective effects of myricitrin against osteoporosis via reducing reactive oxygen species and bone-resorbing cytokines. Toxicol Appl Pharmacol. 2014 Nov 1;280(3):550-60.
• [16] The effect of simvastatin on the proliferation and differentiation of human bone marrow stromal cells. J Korean Med Sci. 2005 Jun;20(3):438-44. doi: 10.3346/jkms.2005.20.3.438.
• [17] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [18] Glucosamine promotes osteogenic differentiation of dental pulp stem cells through modulating the level of the transforming growth factor-beta type I receptor. J Cell Physiol. 2010 Oct;225(1):140-51.
• [19] Pamidronate increases markers of bone formation in patients with multiple myeloma in plateau phase under interferon-alpha treatment. Calcif Tissue Int. 2001 May;68(5):285-90.
• [20] Simvastatin and atorvastatin enhance gene expression of collagen type 1 and osteocalcin in primary human osteoblasts and MG-63 cultures. J Cell Biochem. 2007 Aug 15;101(6):1430-8. doi: 10.1002/jcb.21259.
• [21] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [22] Abnormalities in serum osteocalcin values in children receiving chemotherapy including ifosfamide. In Vivo. 1992 Mar-Apr;6(2):219-21.
• [23] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [24] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [25] Investigation of in vitro odonto/osteogenic capacity of cannabidiol on human dental pulp cell. J Dent. 2021 Jun;109:103673. doi: 10.1016/j.jdent.2021.103673. Epub 2021 Apr 16.
• [26] Hydroxychloroquine decreases human MSC-derived osteoblast differentiation and mineralization in vitro. J Cell Mol Med. 2018 Feb;22(2):873-882. doi: 10.1111/jcmm.13373. Epub 2017 Oct 3.
• [27] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [28] Sensitivity of human dental pulp cells to eighteen chemical agents used for endodontic treatments in dentistry. Odontology. 2013 Jan;101(1):43-51.
• [29] Novel pathways of endocrine disruption through pesticides interference with human mineralocorticoid receptors. Toxicol Sci. 2018 Mar 1;162(1):53-63.
• [30] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [31] Chronic senescent human mesenchymal stem cells as possible contributor to the wound healing disorder after exposure to the alkylating agent sulfur mustard. Arch Toxicol. 2021 Feb;95(2):727-747. doi: 10.1007/s00204-020-02946-5. Epub 2021 Jan 25.
• [32] Statin-mediated reduction of osteopontin expression induces apoptosis and cell growth arrest in ovarian clear cell carcinoma. Oncol Rep. 2011 Jan;25(1):41-7.
• [33] Multifaceted preventive effects of single agent quercetin on a human prostate adenocarcinoma cell line (PC-3): implications for nutritional transcriptomics and multi-target therapy. Med Oncol. 2011 Dec;28(4):1395-404. doi: 10.1007/s12032-010-9603-3. Epub 2010 Jul 2.
• [34] Troglitazone, a PPARgamma ligand, inhibits osteopontin gene expression in human monocytes/macrophage THP-1 cells. J Atheroscler Thromb. 2000;7(2):77-82. doi: 10.5551/jat1994.7.77.
• [35] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [36] Gene microarray analysis of human renal cell carcinoma: the effects of HDAC inhibition and retinoid treatment. Cancer Biol Ther. 2008 Oct;7(10):1607-18.
• [37] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [38] Comparison of base-line and chemical-induced transcriptomic responses in HepaRG and RPTEC/TERT1 cells using TempO-Seq. Arch Toxicol. 2018 Aug;92(8):2517-2531.