Brincidofovir | CMX001 | CAS#444805-28-1 | DNA polymerase inhibitor

MedKoo Cat#: 319653 | Name: Brincidofovir

Description:

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

Brincidofovir, also known as CMX001, HDP-CDV and HDPCDV, is DNA polymerase inhibitor potentially for the treatment of cytomegalovirus, adenovirus, smallpox, and ebolavirus infections. Brincidofovir is a prodrug of cidofovir. Conjugated to a lipid, the compound is designed to release cidofovir intracellularly, allowing for higher intracellular and lower plasma concentrations of cidofovir, effectively increasing its activity against dsDNA viruses, as well as oral bioavailability.

Chemical Structure

Brincidofovir

CAS#444805-28-1

Theoretical Analysis

MedKoo Cat#: 319653

Name: Brincidofovir

CAS#: 444805-28-1

Chemical Formula: C27H52N3O7P

Exact Mass: 561.3543

Molecular Weight: 561.70

Elemental Analysis: C, 57.73; H, 9.33; N, 7.48; O, 19.94; P, 5.51

Price and Availability

Size	Price	Availability
5mg	USD 150.00	Ready to ship
10mg	USD 250.00	Ready to ship
25mg	USD 450.00	Ready to ship
100mg	USD 1,250.00	Ready to ship
1g	USD 4,250.00	Ready to ship
2g	USD 6,850.00	Ready to ship

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Related CAS #

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Synonym

CMX001; CMX 001; CMX-001; HDP-CDV; HDPCDV; Brincidofovir; hexadecyloxypropyl-CDV; 1-O-hexadecyloxypropyl Cidofovir; HDP (S)-HPMPC;

IUPAC/Chemical Name

3-(hexadecyloxy)propyl hydrogen ((((S)-1-(4-amino-2-oxopyrimidin-1(2H)-yl)-3-hydroxypropan-2-yl)oxy)methyl)phosphonate

InChi Key

WXJFKKQWPMNTIM-VWLOTQADSA-N

InChi Code

InChI=1S/C27H52N3O7P/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-19-35-20-16-21-37-38(33,34)24-36-25(23-31)22-30-18-17-26(28)29-27(30)32/h17-18,25,31H,2-16,19-24H2,1H3,(H,33,34)(H2,28,29,32)/t25-/m0/s1

SMILES Code

OC[C@H](CN1C=CC(N)=NC1=O)OCP(O)(OCCCOCCCCCCCCCCCCCCCC)=O

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, not in water

Shelf Life

>2 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

Certificate of Analysis

View CoA: current batch, Lot#A23T04K05

QC Data

View QC data: current batch, Lot#A23T04K05

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

1. Hutson CL, Kondas AV, Mauldin MR, Doty JB, Grossi IM, Morgan CN, Ostergaard SD, Hughes CM, Nakazawa Y, Kling C, Martin BE, Ellison JA, Carroll DS, Gallardo-Romero NF, Olson VA. Pharmacokinetics and Efficacy of a Potential Smallpox Therapeutic, Brincidofovir, in a Lethal Monkeypox Virus Animal Model. mSphere. 2021 Feb 3;6(1):e00927-20. doi: 10.1128/mSphere.00927-20. Erratum in: mSphere. 2021 Feb 17;6(1): PMID: 33536322; PMCID: PMC7860987. 2. Zaitseva M, McCullough KT, Cruz S, Thomas A, Diaz CG, Keilholz L, Grossi IM, Trost LC, Golding H. Postchallenge administration of brincidofovir protects healthy and immune-deficient mice reconstituted with limited numbers of T cells from lethal challenge with IHD-J-Luc vaccinia virus. J Virol. 2015 Mar;89(6):3295-307. doi: 10.1128/JVI.03340-14. Epub 2015 Jan 14. PMID: 25589648; PMCID: PMC4337519.

In vitro activity:

This study investigated the effects of BCV (brincidofovir) in BKPyV-infected and uninfected primary human urothelial cells (HUCs), the target cells of BKPyV in PyVHC. The BCV concentrations causing 50 and 90% reductions (EC50 and EC90) in the number of intracellular BKPyV genome equivalents per cell (icBKPyV) were 0.27 μM and 0.59 μM, respectively. At 0.63 μM, BCV reduced viral late gene expression by 90% and halted progeny release. Reference: Antimicrob Agents Chemother. 2015;59(6):3306-16. https://pubmed.ncbi.nlm.nih.gov/25801568/

In vivo activity:

A three-dose regimen of 20 mg/kg BCV (brincidofovir) administered every 48 h starting either on day 1 or day 2 postchallenge protected 100% of mice. Initiating BCV treatment earlier was more efficient in reducing viral loads and in providing protection from pox lesion development. All BCV-treated mice that survived challenge were also protected from rechallenge with IHD-J-Luc or WRvFire VACV without additional treatment. In immune-deficient mice, BCV protected animals from lethality and reduced viral loads while animals were on the drug. Reference: J Virol. 2015 Mar;89(6):3295-307. https://pubmed.ncbi.nlm.nih.gov/25589648/

	Solvent	mg/mL	mM
Solubility
	DMSO	1.0	1.78

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 561.70 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. Trost LC, Rose ML, Khouri J, Keilholz L, Long J, Godin SJ, Foster SA. The efficacy and pharmacokinetics of brincidofovir for the treatment of lethal rabbitpox virus infection: a model of smallpox disease. Antiviral Res. 2015 May;117:115-21. doi: 10.1016/j.antiviral.2015.02.007. Epub 2015 Mar 4. PMID: 25746331. 2. Tylden GD, Hirsch HH, Rinaldo CH. Brincidofovir (CMX001) inhibits BK polyomavirus replication in primary human urothelial cells. Antimicrob Agents Chemother. 2015;59(6):3306-16. doi: 10.1128/AAC.00238-15. Epub 2015 Mar 23. PMID: 25801568; PMCID: PMC4432119. 3. Hutson CL, Kondas AV, Mauldin MR, Doty JB, Grossi IM, Morgan CN, Ostergaard SD, Hughes CM, Nakazawa Y, Kling C, Martin BE, Ellison JA, Carroll DS, Gallardo-Romero NF, Olson VA. Pharmacokinetics and Efficacy of a Potential Smallpox Therapeutic, Brincidofovir, in a Lethal Monkeypox Virus Animal Model. mSphere. 2021 Feb 3;6(1):e00927-20. doi: 10.1128/mSphere.00927-20. Erratum in: mSphere. 2021 Feb 17;6(1): PMID: 33536322; PMCID: PMC7860987. 4. Zaitseva M, McCullough KT, Cruz S, Thomas A, Diaz CG, Keilholz L, Grossi IM, Trost LC, Golding H. Postchallenge administration of brincidofovir protects healthy and immune-deficient mice reconstituted with limited numbers of T cells from lethal challenge with IHD-J-Luc vaccinia virus. J Virol. 2015 Mar;89(6):3295-307. doi: 10.1128/JVI.03340-14. Epub 2015 Jan 14. PMID: 25589648; PMCID: PMC4337519.

In vitro protocol:

In vivo protocol:

1: Adler H, Gould S, Hine P, Snell LB, Wong W, Houlihan CF, Osborne JC, Rampling T, Beadsworth MB, Duncan CJ, Dunning J, Fletcher TE, Hunter ER, Jacobs M, Khoo SH, Newsholme W, Porter D, Porter RJ, Ratcliffe L, Schmid ML, Semple MG, Tunbridge AJ, Wingfield T, Price NM; NHS England High Consequence Infectious Diseases (Airborne) Network. Clinical features and management of human monkeypox: a retrospective observational study in the UK. Lancet Infect Dis. 2022 Aug;22(8):1153-1162. doi: 10.1016/S1473-3099(22)00228-6. Epub 2022 May 24. Erratum in: Lancet Infect Dis. 2022 Jul;22(7):e177. Erratum in: Lancet Infect Dis. 2022 Jul;22(7):e177. PMID: 35623380; PMCID: PMC9300470. 2: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Brincidofovir. 2022 Oct 18. PMID: 36264877. 3: Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006–. Brincidofovir. 2022 Sep 19. PMID: 35969683. 4: Rizk JG, Lippi G, Henry BM, Forthal DN, Rizk Y. Prevention and Treatment of Monkeypox. Drugs. 2022 Jun;82(9):957-963. doi: 10.1007/s40265-022-01742-y. Epub 2022 Jun 28. Erratum in: Drugs. 2022 Aug;82(12):1343. PMID: 35763248; PMCID: PMC9244487. 5: Huston J, Curtis S, Egelund EF. Brincidofovir: A Novel Agent for the Treatment of Smallpox. Ann Pharmacother. 2023 Jan 23:10600280231151751. doi: 10.1177/10600280231151751. Epub ahead of print. PMID: 36688308. 6: Hutson CL, Kondas AV, Mauldin MR, Doty JB, Grossi IM, Morgan CN, Ostergaard SD, Hughes CM, Nakazawa Y, Kling C, Martin BE, Ellison JA, Carroll DS, Gallardo- Romero NF, Olson VA. Pharmacokinetics and Efficacy of a Potential Smallpox Therapeutic, Brincidofovir, in a Lethal Monkeypox Virus Animal Model. mSphere. 2021 Feb 3;6(1):e00927-20. doi: 10.1128/mSphere.00927-20. Erratum in: mSphere. 2021 Feb 17;6(1): PMID: 33536322; PMCID: PMC7860987. 7: Alvarez-Cardona JJ, Whited LK, Chemaly RF. Brincidofovir: understanding its unique profile and potential role against adenovirus and other viral infections. Future Microbiol. 2020 Apr;15:389-400. doi: 10.2217/fmb-2019-0288. Epub 2020 Mar 13. PMID: 32166967. 8: Ison MG, Hayden RT. Adenovirus. Microbiol Spectr. 2016 Aug;4(4). doi: 10.1128/microbiolspec.DMIH2-0020-2015. PMID: 27726766. 9: Frange P, Leruez-Ville M. Maribavir, brincidofovir and letermovir: Efficacy and safety of new antiviral drugs for treating cytomegalovirus infections. Med Mal Infect. 2018 Dec;48(8):495-502. doi: 10.1016/j.medmal.2018.03.006. Epub 2018 Apr 9. PMID: 29650261. 10: Hill JA, Nichols WG, Marty FM, Papanicolaou GA, Brundage TM, Lanier R, Zerr DM, Boeckh MJ. Oral brincidofovir decreases the incidence of HHV-6B viremia after allogeneic HCT. Blood. 2020 Apr 23;135(17):1447-1451. doi: 10.1182/blood.2019004315. PMID: 32076716; PMCID: PMC7180083. 11: Chan-Tack K, Harrington P, Bensman T, Choi SY, Donaldson E, O'Rear J, McMillan D, Myers L, Seaton M, Ghantous H, Cao Y, Valappil T, Birnkrant D, Struble K. Benefit-risk assessment for brincidofovir for the treatment of smallpox: U.S. Food and Drug Administration's Evaluation. Antiviral Res. 2021 Nov;195:105182. doi: 10.1016/j.antiviral.2021.105182. Epub 2021 Sep 25. PMID: 34582915. 12: Siegrist EA, Sassine J. Antivirals With Activity Against Mpox: A Clinically Oriented Review. Clin Infect Dis. 2023 Jan 6;76(1):155-164. doi: 10.1093/cid/ciac622. PMID: 35904001; PMCID: PMC9825831. 13: Al-Heeti OM, Cathro HP, Ison MG. Adenovirus Infection and Transplantation. Transplantation. 2022 May 1;106(5):920-927. doi: 10.1097/TP.0000000000003988. Epub 2021 Nov 24. PMID: 34856601; PMCID: PMC9050944. 14: Imran M, Alshammari MK, Arora MK, Dubey AK, Das SS, Kamal M, Alqahtani ASA, Sahloly MAY, Alshammari AH, Alhomam HM, Mahzari AM, Abida, Rabaan AA, Dzinamarira T. Oral Brincidofovir Therapy for Monkeypox Outbreak: A Focused Review on the Therapeutic Potential, Clinical Studies, Patent Literature, and Prospects. Biomedicines. 2023 Jan 19;11(2):278. doi: 10.3390/biomedicines11020278. PMID: 36830816; PMCID: PMC9953536. 15: Soheili M, Nasseri S, Afraie M, Khateri S, Moradi Y, Mahdavi Mortazavi SM, Gilzad-Kohan H. Monkeypox: Virology, Pathophysiology, Clinical Characteristics, Epidemiology, Vaccines, Diagnosis, and Treatments. J Pharm Pharm Sci. 2022;25:297-322. doi: 10.18433/jpps33138. PMID: 36130588. 16: Hiwarkar P, Amrolia P, Sivaprakasam P, Lum SH, Doss H, O'Rafferty C, Petterson T, Patrick K, Silva J, Slatter M, Lawson S, Rao K, Steward C, Gassas A, Veys P, Wynn R; United Kingdom Paediatric Bone Marrow Transplant Group. Brincidofovir is highly efficacious in controlling adenoviremia in pediatric recipients of hematopoietic cell transplant. Blood. 2017 Apr 6;129(14):2033-2037. doi: 10.1182/blood-2016-11-749721. Epub 2017 Feb 2. PMID: 28153824. 17: Maffini E, Giaccone L, Festuccia M, Brunello L, Busca A, Bruno B. Treatment of CMV infection after allogeneic hematopoietic stem cell transplantation. Expert Rev Hematol. 2016 Jun;9(6):585-96. doi: 10.1080/17474086.2016.1174571. Epub 2016 Apr 18. PMID: 27043241. 18: Ison MG. Respiratory viral infections in the immunocompromised. Curr Opin Pulm Med. 2022 May 1;28(3):205-210. doi: 10.1097/MCP.0000000000000858. Epub 2022 Jan 31. PMID: 35102093. 19: Guo S, Zhang Y, Liu Z, Wang D, Liu H, Li L, Chen Q, Yang D, Liu Q, Guo H, Mou S, Chen H, Wang X. Brincidofovir is a robust replication inhibitor against African swine fever virus in vivo and in vitro. Emerg Microbes Infect. 2023 Dec;12(2):2220572. doi: 10.1080/22221751.2023.2220572. PMID: 37272334. 20: Sulejmani N, Nagai S, Safwan M, Rizzari MD, Raoufi M, Abouljoud MS, Ramesh M. Brincidofovir as Salvage Therapy for Adenovirus Disease in Intestinal Transplant Recipients. Pharmacotherapy. 2018 Apr;38(4):470-475. doi: 10.1002/phar.2094. Epub 2018 Mar 28. PMID: 29457839.