Dihydrotachysterol

US Previously Marketed

First approved in 1940

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C28H46O
Molecular Weight	398.6642
Optical Activity	UNSPECIFIED
Defined Stereocenters	7 / 7
E/Z Centers	3
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]1(CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C3/C[C@@H](O)CC[C@@H]3C)[C@H](C)\C=C\[C@H](C)C(C)C

InChI

InChIKey=ILYCWAKSDCYMBB-OPCMSESCSA-N

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

HIDE SMILES / InChI

Description
Sources: https://www.drugs.com/mtm/dihydrotachysterol.html
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB01070 | https://www.ncbi.nlm.nih.gov/pubmed/5017770 | https://www.ncbi.nlm.nih.gov/pubmed/468767 | https://www.drugs.com/ingredient/dihydrotachysterol.html

Dihydrotachysterol (DHT) is a synthetic vitamin D analog activated in the liver that does not require renal hydroxylation like vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Dihydrotachysterol is used to treat hypocalcemia, hypoparathyroidism, and prevention of tetany. Dihydrotachysterol is hydroxylated in the liver to 25-hydroxy-dihydrotachysterol, which is the major circulating active form of the drug. Once hydroxylated to 25-hydroxy-dihydrotachysterol, the modified drug binds to the vitamin D receptor. The bound form of the vitamin D receptor serves as a transcriptional regulator of bone matrix proteins, inducing the expression of osteocalcin and suppressing synthesis of type I collagen. Dihydrotachysterol also increases renal phosphate excretion.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Vitamin D receptor 25 Target ID: CHEMBL1977 Sources: https://www.ncbi.nlm.nih.gov/pubmed/468767	Agonist 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypocalcemia 75 Sources: https://www.drugs.com/mtm/dihydrotachysterol.html	Primary		Approved 8429	Hytakerol Approved Use Unknown
Hypoparathyroidism 5 Sources: https://www.drugs.com/mtm/dihydrotachysterol.html	Primary		Approved 8429	Hytakerol Approved Use Unknown

C_max

Value	Dose	Analyte	Population
6.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7988630/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	DIHYDROTACHYSTEROL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
21.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7988630/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	DIHYDROTACHYSTEROL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
22.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7988630/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	DIHYDROTACHYSTEROL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
21.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7988630/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	DIHYDROTACHYSTEROL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
111.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7988630/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	DIHYDROTACHYSTEROL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
195.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7988630/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	DIHYDROTACHYSTEROL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
212.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7988630/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	DIHYDROTACHYSTEROL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
223 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7988630/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	DIHYDROTACHYSTEROL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
7.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7988630/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	DIHYDROTACHYSTEROL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7988630/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	DIHYDROTACHYSTEROL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7988630/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	DIHYDROTACHYSTEROL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7988630/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	DIHYDROTACHYSTEROL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
10 mg 1 times / day multiple, oral Overdose Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/5297643/ Page: p.896, 897	unhealthy, 11 n = 1 Health Status: unhealthy Condition: Hypoparathyroidism Age Group: 11 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/5297643/ Page: p.896, 897	Disc. AE: Hypercalcemia... AEs leading to discontinuation/dose reduction: Hypercalcemia Sources: https://pubmed.ncbi.nlm.nih.gov/5297643/ Page: p.896, 897
4 mg 1 times / day multiple, oral Overdose Dose: 4 mg, 1 times / day Route: oral Route: multiple Dose: 4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12751020/	unhealthy, 31 n = 1 Health Status: unhealthy Condition: Hypoparathyroidism Age Group: 31 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/12751020/	Disc. AE: Hypercalcemia, Renal failure... AEs leading to discontinuation/dose reduction: Hypercalcemia (severe) Renal failure Anemia normocytic Sources: https://pubmed.ncbi.nlm.nih.gov/12751020/
2.5 mL 1 times / day multiple, oral Overdose Dose: 2.5 mL, 1 times / day Route: oral Route: multiple Dose: 2.5 mL, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.2	unhealthy, 74 n = 1 Health Status: unhealthy Condition: Hypoparathyroidism Age Group: 74 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.2	Disc. AE: Confusion, Lethargy... AEs leading to discontinuation/dose reduction: Confusion Lethargy Dysarthria Fatigue Weakness Anorexia Abdominal pain (mild) Hypertension Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.2
2.5 mL 1 times / day multiple, oral Overdose Dose: 2.5 mL, 1 times / day Route: oral Route: multiple Dose: 2.5 mL, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.5	unhealthy, 74 n = 1 Health Status: unhealthy Condition: Hypoparathyroidism Age Group: 74 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.5	Disc. AE: Constipation, Polyuria... AEs leading to discontinuation/dose reduction: Constipation Polyuria Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.5

AEs

AE	Significance	Dose	Population
Hypercalcemia	Disc. AE	10 mg 1 times / day multiple, oral Overdose Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/5297643/ Page: p.896, 897	unhealthy, 11 n = 1 Health Status: unhealthy Condition: Hypoparathyroidism Age Group: 11 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/5297643/ Page: p.896, 897
Anemia normocytic	Disc. AE	4 mg 1 times / day multiple, oral Overdose Dose: 4 mg, 1 times / day Route: oral Route: multiple Dose: 4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12751020/	unhealthy, 31 n = 1 Health Status: unhealthy Condition: Hypoparathyroidism Age Group: 31 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/12751020/
Renal failure	Disc. AE	4 mg 1 times / day multiple, oral Overdose Dose: 4 mg, 1 times / day Route: oral Route: multiple Dose: 4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12751020/	unhealthy, 31 n = 1 Health Status: unhealthy Condition: Hypoparathyroidism Age Group: 31 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/12751020/
Hypercalcemia	severe Disc. AE	4 mg 1 times / day multiple, oral Overdose Dose: 4 mg, 1 times / day Route: oral Route: multiple Dose: 4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12751020/	unhealthy, 31 n = 1 Health Status: unhealthy Condition: Hypoparathyroidism Age Group: 31 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/12751020/
Anorexia	Disc. AE	2.5 mL 1 times / day multiple, oral Overdose Dose: 2.5 mL, 1 times / day Route: oral Route: multiple Dose: 2.5 mL, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.2	unhealthy, 74 n = 1 Health Status: unhealthy Condition: Hypoparathyroidism Age Group: 74 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.2
Confusion	Disc. AE	2.5 mL 1 times / day multiple, oral Overdose Dose: 2.5 mL, 1 times / day Route: oral Route: multiple Dose: 2.5 mL, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.2	unhealthy, 74 n = 1 Health Status: unhealthy Condition: Hypoparathyroidism Age Group: 74 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.2
Dysarthria	Disc. AE	2.5 mL 1 times / day multiple, oral Overdose Dose: 2.5 mL, 1 times / day Route: oral Route: multiple Dose: 2.5 mL, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.2	unhealthy, 74 n = 1 Health Status: unhealthy Condition: Hypoparathyroidism Age Group: 74 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.2
Fatigue	Disc. AE	2.5 mL 1 times / day multiple, oral Overdose Dose: 2.5 mL, 1 times / day Route: oral Route: multiple Dose: 2.5 mL, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.2	unhealthy, 74 n = 1 Health Status: unhealthy Condition: Hypoparathyroidism Age Group: 74 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.2
Hypertension	Disc. AE	2.5 mL 1 times / day multiple, oral Overdose Dose: 2.5 mL, 1 times / day Route: oral Route: multiple Dose: 2.5 mL, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.2	unhealthy, 74 n = 1 Health Status: unhealthy Condition: Hypoparathyroidism Age Group: 74 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.2
Lethargy	Disc. AE	2.5 mL 1 times / day multiple, oral Overdose Dose: 2.5 mL, 1 times / day Route: oral Route: multiple Dose: 2.5 mL, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.2	unhealthy, 74 n = 1 Health Status: unhealthy Condition: Hypoparathyroidism Age Group: 74 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.2
Weakness	Disc. AE	2.5 mL 1 times / day multiple, oral Overdose Dose: 2.5 mL, 1 times / day Route: oral Route: multiple Dose: 2.5 mL, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.2	unhealthy, 74 n = 1 Health Status: unhealthy Condition: Hypoparathyroidism Age Group: 74 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.2
Abdominal pain	mild Disc. AE	2.5 mL 1 times / day multiple, oral Overdose Dose: 2.5 mL, 1 times / day Route: oral Route: multiple Dose: 2.5 mL, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.2	unhealthy, 74 n = 1 Health Status: unhealthy Condition: Hypoparathyroidism Age Group: 74 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.2
Constipation	Disc. AE	2.5 mL 1 times / day multiple, oral Overdose Dose: 2.5 mL, 1 times / day Route: oral Route: multiple Dose: 2.5 mL, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.5	unhealthy, 74 n = 1 Health Status: unhealthy Condition: Hypoparathyroidism Age Group: 74 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.5
Polyuria	Disc. AE	2.5 mL 1 times / day multiple, oral Overdose Dose: 2.5 mL, 1 times / day Route: oral Route: multiple Dose: 2.5 mL, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.5	unhealthy, 74 n = 1 Health Status: unhealthy Condition: Hypoparathyroidism Age Group: 74 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20507648 Page: p.5

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4591	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4591
ZINC	ZINC000004212953	http://zinc15.docking.org/substances/ZINC000004212953

PubMed

Title	Date	PubMed
Pharmacology and therapeutic use of vitamin D and its analogues.	1981 Apr	6262039

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Hypocalcemia: Initial dose: 0.25 to 0.8 mg orally once a day for several days. Maintenance dose: 0.2 to 1 mg orally once a day. Usual Adult Dose for Hypoparathyroidism: Initial dose: 0.8 to 2.4 mg orally once a day for 4 days. Maintenance dose: 0.2 to 1 mg orally once a day. Usual Adult Dose for Hypophosphatemia: Initial dose: 0.8 to 2.4 mg orally once a day for several days. Maintenance dose: 0.2 to 1 mg orally once a day. Usual Adult Dose for Osteoporosis: 0.6 mg orally once a day. Has been used in conjunction with fluoride and calcium. Usual Adult Dose for Renal Osteodystrophy: 0.1 to 0.6 mg orally once a day. Usual Adult Dose for Rickets: 0.5 mg orally one time or 13 to 50 mcg/day until healing occurs. Usual Pediatric Dose for Hypoparathyroidism: Neonate Dose: 0.05 to 0.1 mg orally once a day. Infant and Child Dose: Initial dose: 1 to 5 mg orally once a day for 4 days. Maintenance dose: 0.5 to 1.5 mg orally once a day.

Route of Administration: Oral

In Vitro Use Guide

Primary cultures of mouse calvarial cells were used to Dihydrotachysterol activity evaluation. The cell pellet was obtained by centrifugation at 200 x g for 5 min, then washed thoroughly with large volumes of cold NaCl/Pi to remove traces of culture medium. All subsequent steps were performed at 0-4°C. The washed cell pellets were sonicated on ice in a hypertonic buffer. Cytosol was prepared by centrifugation at 100,000 x g for 1 h at 4°C and adjusted to a protein concentration of 5 to 10 mg/ml. The appropriate steroids, 1,25-(OH)[3H]D3 or 25-(OH)-[3H]D3, were prealiquoted into borosilicate glass tubes (13 x 100 mm) and dried under a stream of N2. The steroids were redissolved in 10 mkl of 100% ethanol prior to cytosol addition. Aliquots of cytosol (0.2 ml) were added to the Dihydrotachysterol and incubated on ice for 3 h. Protein-bound steroid in the cytosol was assayed by chromatography

Name

Type

Language

Dihydrotachysterol

Official Name

English

DIHYDROTACHYSTEROL [USP-RS]

Common Name

English

TACHYSTEROL DIHYDRO DERIVATIVE [MI]

Common Name

English

DIHYDROTACHYSTEROL [USP IMPURITY]

Common Name

English

DIHYDROTACHYSTEROL [MI]

Common Name

English

DIHYDROTACHYSTEROL [JAN]

Common Name

English

DIHYDROTACHYSTEROL [EP MONOGRAPH]

Common Name

English

HYTAKEROL

Brand Name

English

DIHYDROTACHYSTEROL 2

Common Name

English

9,10-SECOERGOSTA-5,7,22-TRIEN-3.BETA.-OL

Common Name

English

Dihydrotachysterol [WHO-DD]

Common Name

English

DIHYDROTACHYSTEROL [EP IMPURITY]

Common Name

English

9,10-SECOERGOSTA-5,7,22-TRIEN-3-OL, (3.BETA.,5E,7E,10.ALPHA.,22E)-

Common Name

English

DIHYDROTACHYSTEROL2

Common Name

English

dihydrotachysterol [INN]

Common Name

English

DIHYDROTACHYSTEROL [HSDB]

Common Name

English

DIHYDROTACHYSTEROL [MART.]

Common Name

English

CYCLOHEXANOL, 4-METHYL-3-((2E)-2-((1R,3AS,7AR)-OCTAHYDRO-7A-METHYL-1-((1R,2E,4R)-1,4,5-TRIMETHYL-2-HEXEN-1-YL)-4H-INDEN-4-YLIDENE)ETHYLIDENE)-, (1S,3E,4S)-

Systematic Name

English

Classification Tree Code System Code

WHO-ATC

A11CC02