APRICITABINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C8H11N3O3S
Molecular Weight	229.256
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC(=O)N(C=C1)[C@H]2CO[C@@H](CO)S2

InChI

InChIKey=RYMCFYKJDVMSIR-RNFRBKRXSA-N

InChI=1S/C8H11N3O3S/c9-5-1-2-11(8(13)10-5)6-4-14-7(3-12)15-6/h1-2,6-7,12H,3-4H2,(H2,9,10,13)/t6-,7-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C8H11N3O3S
Molecular Weight	229.256
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://aidsinfo.nih.gov/drugs/415/apricitabine/0/patient | https://www.ncbi.nlm.nih.gov/pubmed/21054750 | https://www.poz.com/article/hiv-apricitabine-atc-17356-1152 | https://www.ncbi.nlm.nih.gov/pubmed/20007333 | https://www.ncbi.nlm.nih.gov/pubmed/17542150

Apricitabine (ATC) is an investigational drug that was being studied for the treatment of HIV infection. Apricitabine belongs to a class (group) of HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs). NRTIs block an HIV reverse transcriptase. By blocking reverse transcriptase, NRTIs prevent HIV from multiplying and can reduce the amount of HIV in the body. In vitro studies have shown that apricitabine appears to work on certain HIV strains against which other FDA-approved NRTIs, such as lamivudine (brand name: Epivir), may no longer work. Apricitabine shows antiviral activity in vitro against HIV-1 strains and clinical isolates with mutations in the reverse transcriptase that confer resistance to other NRTIs, including M184V, thymidine analogue mutations (TAMs), nucleoside-associated mutations such as L74V and certain mutations at codon 69. Apricitabine has shown activity in treatment-experienced HIV-1-infected patients with NRTI resistance (with M184V and up to five TAMs) as well as in treatment-naive patients. The study of apricitabine as an HIV medicine was discontinued in 2016. The company developing the drug decided to stop their clinical trials due to a lack of funding and a lack of interest in apricitabine’s early access program.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human immunodeficiency virus type 1 reverse transcriptase 67 Target ID: CHEMBL247 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19737995 \| https://www.ncbi.nlm.nih.gov/pubmed/17542154	Inhibitor 8297		0.08 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 151 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19813775 https://aidsinfo.nih.gov/drugs/415/apricitabine/0/patient https://www.ncbi.nlm.nih.gov/pubmed/18211121	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
4920 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18211121	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	APRICITABINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9720 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18211121	800 mg 2 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	APRICITABINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
11500 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18211121	1200 mg 2 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	APRICITABINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
24100 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18211121	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	APRICITABINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
38100 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18211121	800 mg 2 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	APRICITABINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
53200 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18211121	1200 mg 2 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	APRICITABINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
2.45 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18211121	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	APRICITABINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.69 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18211121	800 mg 2 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	APRICITABINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.91 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18211121	1200 mg 2 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	APRICITABINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inducer 781 inhibitor 1587

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYPs 22 P-gp 1461	CYPs 33 UGT1A1 418 OCTs 2 OATs (rOATs) 2	CYPs 12

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/19813775/	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19813775/	no
CYPs 28	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/19813775/	no
CYPs 28	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19813775/	no
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19813775/	weak

Drug as victim

Target	Modality	Activity	Clinical evidence
OATs (rOATs) 2	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21744041/ \| https://pubmed.ncbi.nlm.nih.gov/21989472/ \| https://pubmed.ncbi.nlm.nih.gov/18211616/	likely	yes (co-administration study) Comment: Trimethoprim-sulfamethoxazole increased AUCinf and Cmax by 65.8% and 32.5% Sources: https://pubmed.ncbi.nlm.nih.gov/21744041/ \| https://pubmed.ncbi.nlm.nih.gov/21989472/ \| https://pubmed.ncbi.nlm.nih.gov/18211616/
OCTs 2	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/19813775/ \| https://pubmed.ncbi.nlm.nih.gov/18211616/	likely	yes (co-administration study) Comment: Trimethoprim-sulfamethoxazole increased AUCinf and Cmax by 65.8% and 32.5% Sources: https://pubmed.ncbi.nlm.nih.gov/19813775/ \| https://pubmed.ncbi.nlm.nih.gov/18211616/
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/19813775/	no
CYPs 33	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/19813775/	no
UGT1A1 418	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/17542150/	no

Sourcing

Vendor/Aggregator	ID	URL
AK Scientific	AMTA006	https://aksci.com/item_detail.php?cat=AMTA006
BOC Sciences	160707-69-7	http://www.bocsci.com/description.asp?cas=160707-69-7
Chemspace	CSC010610864	https://chem-space.com/CSC010610864
Chemspace	CSC025702319	https://chem-space.com/CSC025702319
Combi-Blocks	QW-2073	http://www.combi-blocks.com/cgi-bin/find.cgi?QW-2073
Enamine	BBV-45429315	http://www.enaminestore.com/catalog/BBV-45429315
Enamine	BBV-78308303	http://www.enaminestore.com/catalog/BBV-78308303
Hairui	APSA072	http://www.hairuichem.com/en/product/search.do?q=APSA072
KeyOrganics	AS-2749	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-2749
MolPort	MolPort-028-720-520	https://www.molport.com/shop/molecule-link/MolPort-028-720-520
MuseChem	M032709	https://www.musechem.com/product/M032709.html
ShangHai Biochempartner	BCP07907	http://www.biochempartner.com/search_BCP07907
Toronto Research Chemicals	D245513	https://www.trc-canada.com/product-detail/?CatNum=D245513
eMolecules	275110770	https://orderbb.emolecules.com/search/#?query=275110770
eMolecules	300862370	https://orderbb.emolecules.com/search/#?query=300862370
eMolecules	46226846	https://orderbb.emolecules.com/search/#?query=46226846
mcule	MCULE-6056215948	https://mcule.com/MCULE-6056215948/

PubMed

Title	Date	PubMed
Anti-human immunodeficiency virus and anti-hepatitis-B virus activities and toxicities of the enantiomers of 2'-deoxy-3'-oxa-4'-thiocytidine and their 5-fluoro analogues in vitro.	1995 Jan 6	7837220
Drug resistance and drug combination features of the human immunodeficiency virus inhibitor, BCH-10652 [(+/-)-2'-deoxy-3'-oxa-4'-thiocytidine, dOTC].	2000 Jul	10950391
Antiviral activity of 2'-deoxy-3'-oxa-4'-thiocytidine (BCH-10652) against lamivudine-resistant human immunodeficiency virus type 1 in SCID-hu Thy/Liv mice.	2000 Mar	10681360
Selection and characterization of human immunodeficiency virus type 1 variants resistant to the (+) and (-) enantiomers of 2'-deoxy-3'-oxa-4'-thio-5-fluorocytidine.	2000 May	10770740
Selection of resistance-conferring mutations in HIV-1 by the nucleoside reverse transcriptase inhibitors (+/-)dOTC and (+/-)dOTFC.	2000 Nov	11227993
In vitro activity of structurally diverse nucleoside analogs against human immunodeficiency virus type 1 with the K65R mutation in reverse transcriptase.	2005 Mar	15728915
Pharmacokinetics of single oral doses of apricitabine, a novel deoxycytidine analogue reverse transcriptase inhibitor, in healthy volunteers.	2006	17163261
In vitro antiretroviral activity and in vitro toxicity profile of SPD754, a new deoxycytidine nucleoside reverse transcriptase inhibitor for treatment of human immunodeficiency virus infection.	2006 Feb	16436719
Efficacy and tolerability of 10-day monotherapy with apricitabine in antiretroviral-naive, HIV-infected patients.	2006 Jun 12	16816554
Effects of trimethoprim on the clearance of apricitabine, a deoxycytidine analog reverse transcriptase inhibitor, and Lamivudine in the isolated perfused rat kidney.	2006 Nov	16926264
Kinetics of inhibition of HIV type 1 reverse transcriptase-bearing NRTI-associated mutations by apricitabine triphosphate.	2007	17542154
Apricitabine: a novel deoxycytidine analogue nucleoside reverse transcriptase inhibitor for the treatment of nucleoside-resistant HIV infection.	2007	17542150
Gateways to clinical trials.	2007 Jan-Feb	17344945
Effects of apricitabine and other nucleoside reverse transcriptase inhibitors on replication of mitochondrial DNA in HepG2 cells.	2007 Oct	17628710
Multiple-dose pharmacokinetics of apricitabine, a novel nucleoside reverse transcriptase inhibitor, in patients with HIV-1 infection.	2008	18211121
Influence of food on the pharmacokinetics of apricitabine, a novel deoxycytidine analogue reverse transcriptase inhibitor.	2008 Aug	18671458
Pharmacokinetics of apricitabine, a novel nucleoside reverse transcriptase inhibitor, in healthy volunteers treated with trimethoprim-sulphamethoxazole.	2008 Feb	18211616
Apricitabine continues to show good results.	2008 Sep	19043879
Emerging antiviral drugs.	2008 Sep	18764719
Comparison of the pharmacokinetics of apricitabine in the presence and absence of ritonavir-boosted tipranavir: a phase I, open-label, controlled, single-centre study.	2009	19813775
Novel compounds for the treatment of HIV type-1 infection.	2009	19483267
Gateways to clinical trials.	2009 Apr	19536362
Effects of the K65R and K65R/M184V reverse transcriptase mutations in subtype C HIV on enzyme function and drug resistance.	2009 Feb 11	19210791
An analysis of enzyme kinetics data for mitochondrial DNA strand termination by nucleoside reverse transcription inhibitors.	2009 Jan	19132079
Pharmacotherapy of pediatric and adolescent HIV infection.	2009 Jun	19707256
Apricitabine: a nucleoside reverse transcriptase inhibitor for HIV infection.	2009 Oct	19737995
Resistance profile of the new nucleoside reverse transcriptase inhibitor apricitabine.	2010 Feb	20007333

Patents

Sample Use Guides

In Vivo Use Guide

In this Phase II randomized, double-blind study, 51 treatment-experienced HIV-1-infected patients with the reverse transcriptase mutation M184V who were failing therapy which included lamivudine (3TC) were randomized to receive twice-daily 600 mg Apricitabine (ATC), 800 mg ATC or 150 mg 3TC for 21 days.

Route of Administration: Oral

In Vitro Use Guide

Apricitabine (ATC) showed similar activity (IC50: 10–50 uM) against isolates of various group M HIV-1 clades, including A/G, B, C, D, A(E), D/F, F and H.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 15:54:39 GMT 2023` Edited by `admin` on `Sat Dec 16 15:54:39 GMT 2023`
Record UNII	K1YX059ML1
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

APRICITABINE

Official Name

English

AVX-754

Code

English

BCH-10652, (-)-

Code

English

4-AMINO-1-((2R,4R)-2-(HYDROXYMETHYL)-1,3-OXATHIOLAN-4-YL)PYRIMIDIN-2(1H)-ONE

Systematic Name

English

apricitabine [INN]

Common Name

English

BCH-10618

Code

English

SPD -754

Code

English

APRICITABINE [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C97452