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]
Hypoparathyroidism	5A50	Approved	[2]
Hypophosphatemia	N.A.	Approved	[3]
Intestinal hypomagnesemia 1	N.A.	Approved	[4]
Rickets	5B57	Approved	[5]
Autosomal dominant hypocalcemia	5A50.0Y	Investigative	[6]

• Therapeutic Class: Antihypoparathyroid Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 398.7
  Logarithm of the Partition Coefficient (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 [7]
• 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
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

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	[8]

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]	[9]
Rufinamide	DMWE60C	Moderate	Increased metabolism of Dihydrotachysterol caused by Rufinamide mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[9]
Phenobarbital	DMXZOCG	Moderate	Increased metabolism of Dihydrotachysterol caused by Phenobarbital mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[9]
Rifapentine	DMCHV4I	Moderate	Increased metabolism of Dihydrotachysterol caused by Rifapentine mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[9]
Amobarbital	DM0GQ8N	Moderate	Increased metabolism of Dihydrotachysterol caused by Amobarbital mediated induction of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[9]
Orlistat	DMRJSP8	Minor	Decreased absorption of Dihydrotachysterol caused by Orlistat.	Obesity [5B80-5B81]	[10]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] Hypoparathyroidism and pseudo-hypoparathyroidism. Br Med J. 1954 Apr 17;1(4867):903-9.
• [3] 24,25 Dihydroxyvitamin D supplementation corrects hyperparathyroidism and improves skeletal abnormalities in X-linked hypophosphatemic rickets--a clinical research center study. J Clin Endocrinol Metab. 1996 Jun;81(6):2381-8.
• [4] Vitamin D resistance in magnesium deficiency. Am J Clin Nutr. 1976 Aug;29(8):854-8.
• [5] End-organ resistance to 1,25-dihydroxycholecalciferol. Lancet. 1980 Mar 8;1(8167):504-6.
• [6] Feline thyroidectomy. A comparison of postoperative hypocalcemia associated with three different surgical techniques. Vet Surg. 1987 Sep-Oct;16(5):362-6.
• [7] 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
• [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] Product Information. Hectorol (doxercalciferol). Genzyme Corporation, Cambridge, MA.
• [10] Product Information. Xenical (orlistat). Roche Laboratories, Nutley, NJ.