Details of the Drug

General Information of Drug (ID: DMFB97P)

• Drug Name: Dihydrotachysterol
• Synonyms: Antitanil; Calcamine; Dichystrolum; Dihidrotaquisterol; Dihydral; Dihydrotachysterolum; Diidrotachisterolo; Dygratyl; Hytakerol; Parterol; Tachyrol; Tachystin; Dht Intensol; Diidrotachisterolo [DCIT]; AT 10; DHT2; Anti-tetany substance 10; Dht(sub 2); Dihidrotaquisterol [INN-Spanish]; Dihydrotachysterol(sub 2); Dihydrotachysterolum [INN-Latin]; Dihydrotachysterol [INN:BAN:JAN]; (1S,3E,4S)-3-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R,5R)-5,6-dimethylhept-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylcyclohexan-1-ol; (1S,3E,4S)-3-[(2E)-2-[(3aS,7aR)-1-[(E,2R,5R)-5,6-dimethylhept-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylcyclohexan-1-ol; (3E)-3-[(2E)-2-[1-[(E)-5,6-dimethylhept-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylcyclohexan-1-ol; (3S,5E,7E,10S,22E)-9,10-secoergosta-5,7,22-trien-3-ol; (3Z)-3-[(2E)-2-[1-[(E)-5,6-dimethylhept-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylcyclohexan-1-ol; 9,10-Secoergosta-5,7,22-trien-3beta-ol

Indication

Disease Entry	ICD 11	Status	REF
Hypocalcemia	5B5K.1	Approved	[1]

• Therapeutic Class: Antihypoparathyroid Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 398.7
  Topological Polar Surface Area (xlogp); 7.7
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 1
• ADMET Property: MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.0448 micromolar/kg/day [2]
• Chemical Identifiers:
  Formula: C28H46O
  IUPAC Name: (1S,3E,4S)-3-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R,5R)-5,6-dimethylhept-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylcyclohexan-1-ol
  Canonical SMILES: C[C@H]\\1CC[C@@H](C/C1=C\\C=C\\2/CCC[C@]3([C@H]2CC[C@@H]3[C@H](C)/C=C/[C@H](C)C(C)C)C)O
  InChI: InChI=1S/C28H46O/c1-19(2)20(3)9-10-22(5)26-15-16-27-23(8-7-17-28(26,27)6)12-13-24-18-25(29)14-11-21(24)4/h9-10,12-13,19-22,25-27,29H,7-8,11,14-18H2,1-6H3/b10-9+,23-12+,24-13+/t20-,21-,22+,25-,26+,27-,28+/m0/s1
  InChIKey: ILYCWAKSDCYMBB-OPCMSESCSA-N
• Cross-matching ID:
  PubChem CID: 5311071
  ChEBI ID: CHEBI:4591
  CAS Number: 67-96-9
  DrugBank ID: DB01070
  TTD ID: D0G8OC

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	Antagonist	[3], [4]

Molecular Expression Atlas of This Drug

• The Studied Disease: Hypocalcemia
• ICD Disease Classification: 5B5K.1

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Vitamin D3 receptor (VDR)	DTT	VDR	1.69E-02	-0.23	-0.66

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Dihydrotachysterol (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Fosphenytoin	DMOX3LB	Moderate	Increased metabolism of Dihydrotachysterol caused by Fosphenytoin mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[14]
Rufinamide	DMWE60C	Moderate	Increased metabolism of Dihydrotachysterol caused by Rufinamide mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[14]
Phenobarbital	DMXZOCG	Moderate	Increased metabolism of Dihydrotachysterol caused by Phenobarbital mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[14]
Rifapentine	DMCHV4I	Moderate	Increased metabolism of Dihydrotachysterol caused by Rifapentine mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[14]
Amobarbital	DM0GQ8N	Moderate	Increased metabolism of Dihydrotachysterol caused by Amobarbital mediated induction of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[14]
Orlistat	DMRJSP8	Minor	Decreased absorption of Dihydrotachysterol caused by Orlistat.	Obesity [5B80-5B81]	[15]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [3] 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.
• [4] Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1689S-96S.
• [5] Vitamin D in health and disease. Clin J Am Soc Nephrol. 2008 Sep;3(5):1535-41.
• [6] Kaposi sarcoma is a therapeutic target for vitamin D(3) receptor agonist. Blood. 2000 Nov 1;96(9):3188-94.
• [7] Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.
• [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] [Vitamin D2 or vitamin D3]. Rev Med Interne. 2008 Oct;29(10):815-20.
• [11] 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.
• [12] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [13] 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.
• [14] Product Information. Hectorol (doxercalciferol). Genzyme Corporation, Cambridge, MA.
• [15] Product Information. Xenical (orlistat). Roche Laboratories, Nutley, NJ.