Doxercalciferol(1α-Hydroxyvitamin D2)

Molecular Weight (MW)	412.65
Formula	C28H44O2
CAS No.	54573-75-0
Storage	-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)	DMSO: 83 mg/mL (201.1 mM)
Water: <1 mg/mL
Ethanol: 70 mg/mL (169.6 mM)
Other info	Chemical Name: (1S,3R,Z)-5-((E)-2-((1S,3aR,7aS)-1-((2S,5S,E)-5,6-dimethylhept-3-en-2-yl)-7a-methylhexahydro-1H-inden-4(2H)-ylidene)ethylidene)-4-methylenecyclohexane-1,3-diol. InChi Key: HKXBNHCUPKIYDM-UHICYICISA-N InChi Code: InChI=1S/C28H44O2/c1-18(2)19(3)9-10-20(4)25-13-14-26-22(8-7-15-28(25,26)6)11-12-23-16-24(29)17-27(30)21(23)5/h9-12,18-20,24-27,29-30H,5,7-8,13-17H2,1-4,6H3/b10-9+,22-11+,23-12-/t19-,20+,24+,25+,26-,27-,28+/m1/s1 SMILES Code: O[C@@H]1C[C@@H](O)C(/C(C1)=C\C=C2[C@@]3([H])CC[C@@H]([C@H](/C=C/[C@@H](C)C(C)C)C)[C@]3(C)CCC\2)=C
Synonyms	1α-hydroxyvitamin D2; 1α-hydroxy VD2; Doxercalciferol; 1-hydroxy Vitamin D2; Hectorol; 1-Hydroxyergocalciferol; TSA840; TSA-840; TSA 840.

Molecular Weight (MW)

412.65

Formula

C28H44O2

CAS No.

54573-75-0

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 83 mg/mL (201.1 mM)

Water: <1 mg/mL

Ethanol: 70 mg/mL (169.6 mM)

Other info

Chemical Name: (1S,3R,Z)-5-((E)-2-((1S,3aR,7aS)-1-((2S,5S,E)-5,6-dimethylhept-3-en-2-yl)-7a-methylhexahydro-1H-inden-4(2H)-ylidene)ethylidene)-4-methylenecyclohexane-1,3-diol.
InChi Key: HKXBNHCUPKIYDM-UHICYICISA-N
InChi Code: InChI=1S/C28H44O2/c1-18(2)19(3)9-10-20(4)25-13-14-26-22(8-7-15-28(25,26)6)11-12-23-16-24(29)17-27(30)21(23)5/h9-12,18-20,24-27,29-30H,5,7-8,13-17H2,1-4,6H3/b10-9+,22-11+,23-12-/t19-,20+,24+,25+,26-,27-,28+/m1/s1
SMILES Code: O[C@@H]1C[C@@H](O)C(/C(C1)=C\C=C2[C@@]3([H])CC[C@@H]([C@H](/C=C/[C@@H](C)C(C)C)C)[C@]3(C)CCC\2)=C

Synonyms

1α-hydroxyvitamin D2; 1α-hydroxy VD2; Doxercalciferol; 1-hydroxy Vitamin D2; Hectorol; 1-Hydroxyergocalciferol; TSA840; TSA-840; TSA 840.

In Vitro	In vitro activity: Doxercalciferol (100 or 300 pg/g b.w.) normalizes serum calcium and parathyroid hormone (PTH) levels in nephrectomy treated mice. Doxercalciferol (300 pg/g b.w.) significantly reduces osteitis fibrosa in nephrectomy treated mice. Doxercalciferol results in significant decrease in cardiac hypertrophy and improves cardiac function in rats fed a high salt (HS) diet. Doxercalciferol treatment leads to a significant decrease in plasma brain natriuretic peptide (BNP) level and tissue atrial natriuretic factor (ANF) mRNA level in rats fed a high salt (HS) diet. Doxercalciferol also significantly reduces the level of protein kinase C-α (PKCα) suggesting that PKC-mediated cardiac hypertrophy may be associated with vitamin D deficiency. Doxercalciferol decreases proteinuria, podocyte injury, mesangial expansion, and extracellular matrix protein accumulation in Diet-induced obesity (DIO) mice. Doxercalciferol also decreases macrophage infiltration, oxidative stress, proinflammatory cytokines, and profibrotic growth factors in DIO mice. Doxercalciferol also prevents the activation of the renin-angiotensin-aldosterone system including the angiotensin II type 1 receptor and the mineralocorticoid receptor in DIO mice. Doxercalciferol combined with Losartan most effectively prevents albuminuria, restored glomerular filtration barrier structure, and dramatically reduces glomerulosclerosis in a dose-dependent manner in mice. Doxercalciferol combined with Losartan virtually prevents morphological and molecular changes in diabetic kidneys of mice
In Vivo	Doxercalciferol (0.083, 0.167 or 0.333 μg/kg, i.p.) elevates serum phosphorus at Week 6 in 5/6 nephrectomized (NX) rats. Doxercalciferol (0.167 and 0.333 μg/kg) also increases serum calcium and Ca × P at Weeks 2 and 6, and enhances increased pulse wave velocity (PWV) at Week 6 in 5/6 nephrectomized (NX) rats. Doxercalciferol blocks PTH from rising at 0.083 μg/kg, and lowers serum PTH to the SHAM level[1]. Doxercalciferol (125 ng/kg, i.p. thrice per week) increases expression of VDR mRNA level and renal expression of TRPV5 in NON mice fed a HF diet. Doxercalciferol also improves proteinuria, prevents loss of podocytes, and accumulation of extracellular matrix proteins in HF diet-induced mice. Doxercalciferol inhibits the expression of profibrotic growth factors (TGF-β, PAI-1, and connective tissue growth factor (CTGF)), and blocks increased expression of the renin-angiotensin-aldosterone system in mice fed a HF diet. Furthermore, Doxercalciferol suppresses macrophage infiltration, decreases NF-κb activity, and preventes expression of proinflammatory cytokine and the increase in renal lipid accumulation in mice fed a HF diet. Doxercalciferol (30 ng/kg, i.p. thrice per week) prevents albuminuria, markedly attenuates podocyte loss and apoptosis, and reduces glomerular fibrosis in streptozotocin-induced diabetic mice
Animal model	Rats: Male, Sprague-Dawley, 5/6 nephrectomized (NX) rats (~200 gm) are used 1 week after nephrectomy. The nephrectomy is performed using a standard two-step surgical ablation procedure. Beginning 2 weeks post-nephrectomy, rats are maintained on a high phosphorus diet (0.9% phosphorus and 0.6% calcium) for the duration of the study to induce secondary hyperparathyroidism. On Day 0, SHAM and 5/6 NX rats (n = 7-10 per group) receive vehicle (5% EtOH/95% propylene glycol; 0.4 mL/kg; i.p.) or VDRA (paricalcitol or Doxercalciferol; 0.083, 0.167 or 0.333 μg/kg; intraperitoneally) three times per week for 41 days (n = 6-10 per group). These doses are chosen based on the fact that lower doses (0.021 and 0.042 μg/kg; i.p.) of either compound are not PTH suppressive after 2 or 6 weeks of treatment in this model of CKD. On Days 0, 13 and 41, blood is collected (24 h post-dose). On Days 0, 13 and 41 (24 h post-dose), animals are anaesthetized with ketamine (50 mg/kg) and blood is collected via the tail vein for PTH and serum blood chemistry determinations
Formulation & Dosage	0.083, 0.167 or 0.333 μg/kg, i.p.
References	Nephron Exp Nephrol. 2011;119(3):e67-74; J Card Fail. 2011 Dec;17(12):1051-8; Am J Physiol Renal Physiol. 2011 Mar;300(3):F801-10; Nephrol Dial Transplant. 2008 Dec;23(12):3824-30.

In Vitro

In vitro activity: Doxercalciferol (100 or 300 pg/g b.w.) normalizes serum calcium and parathyroid hormone (PTH) levels in nephrectomy treated mice. Doxercalciferol (300 pg/g b.w.) significantly reduces osteitis fibrosa in nephrectomy treated mice. Doxercalciferol results in significant decrease in cardiac hypertrophy and improves cardiac function in rats fed a high salt (HS) diet. Doxercalciferol treatment leads to a significant decrease in plasma brain natriuretic peptide (BNP) level and tissue atrial natriuretic factor (ANF) mRNA level in rats fed a high salt (HS) diet. Doxercalciferol also significantly reduces the level of protein kinase C-α (PKCα) suggesting that PKC-mediated cardiac hypertrophy may be associated with vitamin D deficiency. Doxercalciferol decreases proteinuria, podocyte injury, mesangial expansion, and extracellular matrix protein accumulation in Diet-induced obesity (DIO) mice. Doxercalciferol also decreases macrophage infiltration, oxidative stress, proinflammatory cytokines, and profibrotic growth factors in DIO mice. Doxercalciferol also prevents the activation of the renin-angiotensin-aldosterone system including the angiotensin II type 1 receptor and the mineralocorticoid receptor in DIO mice. Doxercalciferol combined with Losartan most effectively prevents albuminuria, restored glomerular filtration barrier structure, and dramatically reduces glomerulosclerosis in a dose-dependent manner in mice. Doxercalciferol combined with Losartan virtually prevents morphological and molecular changes in diabetic kidneys of mice

In Vivo

Doxercalciferol (0.083, 0.167 or 0.333 μg/kg, i.p.) elevates serum phosphorus at Week 6 in 5/6 nephrectomized (NX) rats. Doxercalciferol (0.167 and 0.333 μg/kg) also increases serum calcium and Ca × P at Weeks 2 and 6, and enhances increased pulse wave velocity (PWV) at Week 6 in 5/6 nephrectomized (NX) rats. Doxercalciferol blocks PTH from rising at 0.083 μg/kg, and lowers serum PTH to the SHAM level[1]. Doxercalciferol (125 ng/kg, i.p. thrice per week) increases expression of VDR mRNA level and renal expression of TRPV5 in NON mice fed a HF diet. Doxercalciferol also improves proteinuria, prevents loss of podocytes, and accumulation of extracellular matrix proteins in HF diet-induced mice. Doxercalciferol inhibits the expression of profibrotic growth factors (TGF-β, PAI-1, and connective tissue growth factor (CTGF)), and blocks increased expression of the renin-angiotensin-aldosterone system in mice fed a HF diet. Furthermore, Doxercalciferol suppresses macrophage infiltration, decreases NF-κb activity, and preventes expression of proinflammatory cytokine and the increase in renal lipid accumulation in mice fed a HF diet. Doxercalciferol (30 ng/kg, i.p. thrice per week) prevents albuminuria, markedly attenuates podocyte loss and apoptosis, and reduces glomerular fibrosis in streptozotocin-induced diabetic mice

Animal model

Rats: Male, Sprague-Dawley, 5/6 nephrectomized (NX) rats (~200 gm) are used 1 week after nephrectomy. The nephrectomy is performed using a standard two-step surgical ablation procedure. Beginning 2 weeks post-nephrectomy, rats are maintained on a high phosphorus diet (0.9% phosphorus and 0.6% calcium) for the duration of the study to induce secondary hyperparathyroidism. On Day 0, SHAM and 5/6 NX rats (n = 7-10 per group) receive vehicle (5% EtOH/95% propylene glycol; 0.4 mL/kg; i.p.) or VDRA (paricalcitol or Doxercalciferol; 0.083, 0.167 or 0.333 μg/kg; intraperitoneally) three times per week for 41 days (n = 6-10 per group). These doses are chosen based on the fact that lower doses (0.021 and 0.042 μg/kg; i.p.) of either compound are not PTH suppressive after 2 or 6 weeks of treatment in this model of CKD. On Days 0, 13 and 41, blood is collected (24 h post-dose). On Days 0, 13 and 41 (24 h post-dose), animals are anaesthetized with ketamine (50 mg/kg) and blood is collected via the tail vein for PTH and serum blood chemistry determinations

Formulation & Dosage

0.083, 0.167 or 0.333 μg/kg, i.p.

References

Nephron Exp Nephrol. 2011;119(3):e67-74; J Card Fail. 2011 Dec;17(12):1051-8; Am J Physiol Renal Physiol. 2011 Mar;300(3):F801-10; Nephrol Dial Transplant. 2008 Dec;23(12):3824-30.

CAS NO:	54573-75-0
规格:	≥98%

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