Darunavir ethanolate | CAS# 635728-49-3 | inhibitor

MedKoo Cat#: 574651 | Name: Darunavir ethanolate

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

Chemical Structure

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
100mg	USD 450.00	2 Weeks
250mg	USD 850.00	2 Weeks
1g	USD 1,650.00	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

More Info

Product Data

Product Data

Instruction

View handling instruction

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/

	Solvent	mg/mL	mM
Solubility
	DMSO	75.0	126.32

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.

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:

In vivo protocol:

1: Darwish IA, Al-Majed AA, Alsaif NA, Bakheit AH, Herqash RN, Alzaid A. Darunavir: A comprehensive profile. Profiles Drug Subst Excip Relat Methodol. 2021;46:1-50. doi: 10.1016/bs.podrm.2020.07.001. Epub 2020 Aug 21. PMID: 33461696. 2: Pope R Jr, Kashuba A. Darunavir for use in pregnant women with HIV. Expert Rev Clin Pharmacol. 2017 Dec;10(12):1317-1327. doi: 10.1080/17512433.2017.1390428. Epub 2017 Nov 14. PMID: 28988509. 3: Deeks ED. Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. Drugs. 2018 Jul;78(10):1013-1024. doi: 10.1007/s40265-018-0934-2. PMID: 29915897. 4: Paton NI, Musaazi J, Kityo C, Walimbwa S, Hoppe A, Balyegisawa A, Kaimal A, Mirembe G, Tukamushabe P, Ategeka G, Hakim J, Mugerwa H, Siika A, Asienzo J, Castelnuovo B, Kiragga A, Kambugu A; NADIA Trial Team. Dolutegravir or Darunavir in Combination with Zidovudine or Tenofovir to Treat HIV. N Engl J Med. 2021 Jul 22;385(4):330-341. doi: 10.1056/NEJMoa2101609. PMID: 34289276. 5: Keating GM. Darunavir: A Review in Pediatric HIV-1 Infection. Paediatr Drugs. 2015 Oct;17(5):411-21. doi: 10.1007/s40272-015-0146-0. PMID: 26323490. 6: Spagnuolo V, Castagna A, Lazzarin A. Darunavir for the treatment of HIV infection. Expert Opin Pharmacother. 2018 Jul;19(10):1149-1163. doi: 10.1080/14656566.2018.1484901. Epub 2018 Jun 18. PMID: 29913082. 7: Ghosh AK, Weber IT, Mitsuya H. Beyond darunavir: recent development of next generation HIV-1 protease inhibitors to combat drug resistance. Chem Commun (Camb). 2022 Oct 20;58(84):11762-11782. doi: 10.1039/d2cc04541a. PMID: 36200462. 8: Kakuda TN, Crauwels H, Opsomer M, Tomaka F, van de Casteele T, Vanveggel S, Iterbeke K, de Smedt G. Darunavir/cobicistat once daily for the treatment of HIV. Expert Rev Anti Infect Ther. 2015 Jun;13(6):691-704. doi: 10.1586/14787210.2015.1033400. PMID: 25962100. 9: Curran A, Pérez-Valero I, Moltó J. Rezolsta® (Darunavir/Cobicistat): First Boosted Protease Inhibitor Co-formulated with Cobicistat. AIDS Rev. 2015 Apr- Jun;17(2):114-20. PMID: 26035169. 10: Mallolas J. Darunavir Stands Up as Preferred HIV Protease Inhibitor. AIDS Rev. 2017 Apr-Jun;19(2):105-112. PMID: 28664942. 11: Clotet B. Introducción [Introduction. Darunavir]. Enferm Infecc Microbiol Clin. 2008 Oct;26 Suppl 10:1-2. Spanish. doi: 10.1016/s0213-005x(08)76546-7. PMID: 19195452. 12: Khoo S, Peytavin G, Burger D, Hill A, Brown K, Moecklinghoff C, La Porte C, Hadacek MB. Pharmacokinetics and Safety of Darunavir/Ritonavir in HIV-Infected Pregnant Women. AIDS Rev. 2017 Jan-Mar;19(1):16-23. PMID: 28182610. 13: González-Domenech CM, Palacios R, Santos J. Aspectos farmacológicos de darunavir/cobicistat [Pharmacological aspects of darunavir/cobicistat]. Enferm Infecc Microbiol Clin. 2016 May;34 Suppl 1:30-33. Spanish. doi: 10.1016/S0213-005X(17)30006-X. PMID: 28081761. 14: Llibre JM. Development of darunavir over the entire spectrum of HIV infection. Enferm Infecc Microbiol Clin (Engl Ed). 2018 Dec;36 Suppl 2:3-9. English, Spanish. doi: 10.1016/S0213-005X(18)30391-4. PMID: 30545469. 15: Capetti A, Cossu MV, Rizzardini G. Darunavir/cobicistat for the treatment of HIV-1: a new era for compact drugs with high genetic barrier to resistance. Expert Opin Pharmacother. 2015;16(17):2689-702. doi: 10.1517/14656566.2015.1109632. Epub 2015 Nov 27. PMID: 26612518. 16: Squillace N, Bozzi G, Colella E, Gori A, Bandera A. Darunavir-cobicistat- emtricitabine-tenofovir alafenamide: safety and efficacy of a protease inhibitor in the modern era. Drug Des Devel Ther. 2018 Oct 29;12:3635-3643. doi: 10.2147/DDDT.S147493. PMID: 30464395; PMCID: PMC6211373. 17: Molina JM, Squires K, Sax PE, Cahn P, Lombaard J, DeJesus E, Lai MT, Rodgers A, Lupinacci L, Kumar S, Sklar P, Hanna GJ, Hwang C, Martin EA; DRIVE-FORWARD trial group. Doravirine versus ritonavir-boosted darunavir in antiretroviral- naive adults with HIV-1 (DRIVE-FORWARD): 96-week results of a randomised, double-blind, non-inferiority, phase 3 trial. Lancet HIV. 2020 Jan;7(1):e16-e26. doi: 10.1016/S2352-3018(19)30336-4. Epub 2019 Nov 15. PMID: 31740348. 18: Triant VA, Siedner MJ. Darunavir and Cardiovascular Risk: Evaluating the Data to Inform Clinical Care. J Infect Dis. 2020 Feb 3;221(4):498-500. doi: 10.1093/infdis/jiz482. PMID: 31828327; PMCID: PMC6996858. 19: Eke AC, Stek AM, Wang J, Kreitchmann R, Shapiro DE, Smith E, Chakhtoura N, Capparelli EV, Mirochnick M, Best BM; IMPAACT P1026s Protocol Team. Darunavir Pharmacokinetics With an Increased Dose During Pregnancy. J Acquir Immune Defic Syndr. 2020 Apr 1;83(4):373-380. doi: 10.1097/QAI.0000000000002261. PMID: 31923087; PMCID: PMC7258985. 20: Rubio R, Matarranz M, Bisbal O, de Lagarde M, Domínguez L. Efectividad y seguridad de darunavir a largo plazo [Long-term safety and effectiveness of darunavir]. Enferm Infecc Microbiol Clin. 2016 May;34 Suppl 1:16-22. Spanish. doi: 10.1016/S0213-005X(17)30004-6. PMID: 28081758.