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			MedGen

  Source:		MedGen UID: 835861


     		Brincidofovir

			Definition
			An alkoxyalkyl ester prodrug containing the
			synthetic, acyclic nucleoside monophosphate
			analog cidofovir linked, through its phosphonate
			group, to a lipid, 3-hexadecyloxy-1-propanol,
			with antiviral activity against double-stranded
			DNA viruses. Upon oral administration,
			brincidofovir crosses the intestinal wall and
			penetrates target viral-infected cells before
			being cleaved to the free antiviral agent
			cidofovir. In turn, cidofovir is phosphorylated by
			pyruvate kinases to its active metabolite
			cidofovir diphosphate. Cidofovir diphosphate,
			bearing structural similarity to nucleotides,
			competes with deoxycytosine-5-triphosphate
			(dCTP) for viral DNA polymerase and gets
			incorporated into the growing viral DNA
			strands. As a result, it prevents further DNA
			polymerization and disrupts DNA replication of
			viruses. Compared to cidofovir, which is given
			intravenously, hexadecyloxypropyl-cidofovir
			shows better oral bioavailability, less toxicity
			and enhanced cellular penetration.

			Related Concepts
			oral

			PubMed
			31157669 Updates on antiviral drugs for
			cytomegalovirus prevention and treatment.

			31132546 New vaccines and antiviral drugs for
			cytomegalovirus.

			31116132 Approach to infection and disease
			due to adenoviruses in solid organ
			transplantation.

			31046707 Anti-Ebola therapy for patients with
			Ebola virus disease: a systematic review.

			30969265 Brincidofovir as a Salvage Therapy in
			Controlling Adenoviremia in Pediatric Recipients
			of Hematopoietic Stem Cell Transplant.

			30677427 In vitro comparison of currently
			available and investigational antiviral agents
			against pathogenic human double-stranded
			DNA viruses: A systematic literature review.

			30546071 A survey on incidence and
			management of adenovirus infection after
			allogeneic HSCT.

			30529090 Antiviral activity of brincidofovir on
			parvovirus B19.

			30397065 Cidofovir Diphosphate Inhibits
			Adenovirus 5 DNA Polymerase via Both
			Non-Obligate Chain Termination and Direct
			Inhibition, and Polymerase Mutations Confer
			Cidofovir Resistance on Intact Virus.

			30292744 A randomized, double-blind,
			placebo-controlled phase 3 trial of oral
			brincidofovir for cytomegalovirus prophylaxis in
			allogeneic hematopoietic-cell transplantation.

			30154125 Antiviral prophylaxis for
			cytomegalovirus infection in allogeneic
			hematopoietic cell transplantation.

			30153445 In vitro evaluation of current and
			novel antivirals in combination against human
			cytomegalovirus.

			30120866 Efficacy of Brincidofovir as
			prophylaxis against HSV and VZV in
			hematopoietic cell transplant recipients.

			30004790 Letermovir for the prevention of
			cytomegalovirus infection in adult
			cytomegalovirus-seropositive hematopoietic
			stem cell transplant recipients.

			29846280 Brincidofovir (CMX001) Toxicity
			Associated With Epithelial Apoptosis and Crypt
			Drop Out in a Hematopoietic Cell Transplant
			Patient: Challenges in Distinguishing Drug
			Toxicity From GVHD.

			29846196 Adenovirus infection in pediatric
			transplant recipients: are effective antiviral
			agents coming our way?

			29842914 Genetic diversity of the human
			adenovirus species C DNA polymerase.

			29777868 Comparative Efficacy and Safety of
			Different Antiviral Agents for Cytomegalovirus
			Prophylaxis in Allogeneic Hematopoietic-Cell
			Transplantation: a Systematic Review and
			Meta-Analysis.

			29773767 The Role of Brincidofovir in
			Preparation for a Potential Smallpox Outbreak.

			29742642 Successful Brincidofovir Treatment
			of Metagenomics-Detected Adenovirus
			Infection in a Severely Ill STAT1-Deficient
			Patient.

			Clinical Trials
			3532035 Open Label Study of IV Brincidofovir
			in Adult Transplant Recipients With Adenovirus
			Viremia

			3481244 Treatment of Adenovirus
			Disseminated Infections in Hematopoietic Stem
			Cell Transplant Patients With Adenovirus
			Digestive Replication

			2596997 Expanded Access Protocol to Provide
			Brincidofovir for the Treatment of Serious
			Adenovirus Infection or Disease

			2439970 SUSTAIN: A Randomized,
			Double-Blind, Multicenter, Phase 3 Study of the
			Efficacy, Safety, and Tolerability of Brincidofovir
			Versus Valganciclovir for the Prevention of
			Cytomegalovirus Disease in CMV Seronegative
			Kidney Allograft Recipients

			2439957 SURPASS: A Randomized,
			Double-Blind, Multicenter Study of the Efficacy,
			Safety, and Tolerability of Brincidofovir Versus
			Valganciclovir for the Prevention of
			Cytomegalovirus (CMV) Disease in CMV
			Seropositive Kidney Transplant Recipients (BCV
			CMV vGCV)

			2271347 An Open-Label, Multicenter Study of
			the Safety and Anti Viral Activity of Brincidofovir
			(BCV, CMX001) for Ebola Virus Disease

			2087306 Phase III, Open-labeled, Multicenter
			Study of the Safety and Efficacy of Brincidofovir
			(CMX001) in the Treatment of Early Versus Late
			Adenovirus Infection

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