Darunavir ethanolate
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MedKoo CAT#: 574651

CAS#: 635728-49-3 (ethanolate)

Description: Darunavir ethanolate is an inhibitor active against HIV-1 clinical isolates with minimal cytotoxicity.


Chemical Structure

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Darunavir ethanolate
CAS# 635728-49-3 (ethanolate)

Theoretical Analysis

MedKoo Cat#: 574651
Name: Darunavir ethanolate
CAS#: 635728-49-3 (ethanolate)
Chemical Formula: C29H43N3O8S
Exact Mass: 593.2771
Molecular Weight: 593.74
Elemental Analysis: C, 58.67; H, 7.30; N, 7.08; O, 21.56; S, 5.40

Price and Availability

Size Price Availability Quantity
5.0mg USD 230.0 2 Weeks
10.0mg USD 380.0 2 Weeks
50.0mg USD 735.0 2 Weeks
100.0mg USD 1100.0 2 Weeks
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Related CAS #: 2281870-65-1 (dihydrate)   635728-49-3 (ethanolate)   206361-99-1 (free)  

Synonym: Darunavir ethanolate; TMC114 ethanolate

IUPAC/Chemical Name: (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ((2S,3R)-4-((4-amino-N-isobutylphenyl)sulfonamido)-3-hydroxy-1-phenylbutan-2-yl)carbamate compound with ethanol (1:1)

InChi Key: QWSHKNICRJHQCY-VBTXLZOXSA-N

InChi Code: InChI=1S/C27H37N3O7S.C2H6O/c1-18(2)15-30(38(33,34)21-10-8-20(28)9-11-21)16-24(31)23(14-19-6-4-3-5-7-19)29-27(32)37-25-17-36-26-22(25)12-13-35-26;1-2-3/h3-11,18,22-26,31H,12-17,28H2,1-2H3,(H,29,32);3H,2H2,1H3/t22-,23-,24+,25-,26+;/m0./s1

SMILES Code: O=C(O[C@@H]1[C@@]2([H])[C@@](OCC2)([H])OC1)N[C@@H](CC3=CC=CC=C3)[C@H](O)CN(S(=O)(C4=CC=C(N)C=C4)=O)CC(C)C.CCO

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >3 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Product Data:

Biological target: Darunavir ethanolate (TMC114 Ethanolate) is a potent HIV protease inhibitor used to treat and prevent HIV/AIDS. Darunavir has a Ki of 1 nM for wild type HIV-1 protease.
In vitro activity: To test whether DRV (Darunavir) can protect kidney cells from the deleterious effects of HIV via HIV protease-independent mechanisms, the effects of DRV on renal tubular epithelial cells (RTEC) were studied. Conditionally immortalized human RTEC (HPT1b cells) were transduced with lentiviral vectors encoding either gag/pol-deleted HIV (based on the same provirus used in Tg26 HIVAN model, which lacks HIV protease), Vpr, or control lentivirus expressing EGFP and subsequently treated with DRV or vehicle control. HIV and Vpr-transduction of HPT1b cells increased phosphorylation of Stat3 (p < 0.01), Src (p < 0.01), and Erk (p < 0.01) compared to cells transduced with EGFP control lentivirus and DRV significantly prevented HIV and Vpr-induced phosphorylation of Stat3 (p < 0.01), Src (p < 0.01), and Erk (p < 0.01) (Fig. 1A,B). Since HIV-induced expression of proinflammatory mediators, including IL-6 and IL-8 are critical mediators of HIVAN pathogenesis35, we analyzed IL-6 and IL-8 expression in control, HIV- and Vpr-transfected HPT1b cells treated with or without DRV (Fig. 1C). HIV and Vpr transduction increased the expression of IL-6 (p < 0.01 and p = 0.03 respectively) and IL-8 (p < 0.01) in HPT1b cells compared to control-transduced cells. HIV and Vpr-induced upregulation of IL-6 and IL-8 was abrogated by DRV (Fig. 1C, p < 0.01). Reference: Sci Rep. 2019; 9: 15857. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825220/
In vivo activity: It was next studied whether DRV can protect HIV-transgenic mice from developing the HIVAN phenotype. Four-month-old heterozygous Tg26-FVB mice were assigned to 4 treatment groups and were treated daily by oral gavage for 5 weeks with DRV, AZT, DRV + AZT, or vehicle control. Control-treated Tg26 mice developed typical histopathologic findings of HIVAN, whereas glomerulosclerosis and tubulointerstitial injury were improved in Tg26 treated with DRV. Quantitative histomorphometry demonstrated that DRV and DRV + AZT groups had significantly reduced glomerulosclerosis (Fig. 2B, p = 0.015, and p = 0.029, respectively), tubular cast formation (Fig. 2C, p = 0.023 and p = 0.048, respectively), interstitial fibrosis and tubular atrophy (Fig. 2D, p = 0.025 and p = 0.017, respectively), and interstitial inflammation (Fig. 2E, p = 0.012 and p = 0.013, respectively) compared to vehicle-treated mice. kidneys from Tg26 mice treated with vehicle control (Fig. 5A) or AZT had markedly increased levels of p-Stat3, whereas levels were similar to wild-type in DRV or DRV + AZT treated Tg26 mice. Similarly, p-Src and p-Erk were increased in kidneys of Tg26 mice treated with vehicle control or AZT, but not in those treated with DRV or DRV + AZT (Fig. 5A). Reference: Sci Rep. 2019; 9: 15857. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825220/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 75.0 126.32

Preparing Stock Solutions

The following data is based on the product molecular weight 593.74 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Gao X, Rosales A, Karttunen H, Bommana GM, Tandoh B, Yi Z, Habib Z, D'Agati V, Zhang W, Ross MJ. The HIV protease inhibitor darunavir prevents kidney injury via HIV-independent mechanisms. Sci Rep. 2019 Nov 1;9(1):15857. doi: 10.1038/s41598019-52278-3. Erratum in: Sci Rep. 2020 Mar 4;10(1):4345. PMID: 31676833; PMCID: PMC6825220.
In vitro protocol: 1. Gao X, Rosales A, Karttunen H, Bommana GM, Tandoh B, Yi Z, Habib Z, D'Agati V, Zhang W, Ross MJ. The HIV protease inhibitor darunavir prevents kidney injury via HIV-independent mechanisms. Sci Rep. 2019 Nov 1;9(1):15857. doi: 10.1038/s41598019-52278-3. Erratum in: Sci Rep. 2020 Mar 4;10(1):4345. PMID: 31676833; PMCID: PMC6825220.
In vivo protocol: 1. Gao X, Rosales A, Karttunen H, Bommana GM, Tandoh B, Yi Z, Habib Z, D'Agati V, Zhang W, Ross MJ. The HIV protease inhibitor darunavir prevents kidney injury via HIV-independent mechanisms. Sci Rep. 2019 Nov 1;9(1):15857. doi: 10.1038/s41598019-52278-3. Erratum in: Sci Rep. 2020 Mar 4;10(1):4345. PMID: 31676833; PMCID: PMC6825220.

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1. Tie Y, et al. High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains. J Mol Biol. 2004 Apr 23;338(2):341-52.

2. McKeage K, et al. Darunavir: a review of its use in the management of HIV infection in adults. Drugs. 2009;69(4):477-503.

3. Bhalekar MR, et al. In-vivo bioavailability and lymphatic uptake evaluation of lipid nanoparticulates of darunavir. Drug Deliv. 2016 Sep;23(7):2581-2586.