APRICITABINE, (±)-

Details

Stereochemistry	RACEMIC
Molecular Formula	C8H11N3O3S
Molecular Weight	229.256
Optical Activity	( + / - )
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
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
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
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
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
An analysis of enzyme kinetics data for mitochondrial DNA strand termination by nucleoside reverse transcription inhibitors.	2009 Jan	19132079

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 `Fri Dec 15 16:22:31 GMT 2023` Edited by `admin` on `Fri Dec 15 16:22:31 GMT 2023`
Record UNII	DND9Y3G72C
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

APRICITABINE, (±)-

Common Name

English

2(1H)-PYRIMIDINONE, 4-AMINO-1-((2R,4R)-2-(HYDROXYMETHYL)-1,3-OXATHIOLAN-4-YL)-, REL-

Systematic Name

English

DOTC, CIS-(±)-

Common Name

English

BCH-10652

Code

English

2'-DEOXY-3'-OXA-4'-THIOCYTIDINE, CIS-

Common Name

English

Code System Code Type Description

PUBCHEM

455041

Created by admin on Fri Dec 15 16:22:31 GMT 2023 , Edited by admin on Fri Dec 15 16:22:31 GMT 2023

PRIMARY

FDA UNII

DND9Y3G72C

Created by admin on Fri Dec 15 16:22:31 GMT 2023 , Edited by admin on Fri Dec 15 16:22:31 GMT 2023

PRIMARY

CAS

143338-12-9

Created by admin on Fri Dec 15 16:22:31 GMT 2023 , Edited by admin on Fri Dec 15 16:22:31 GMT 2023

PRIMARY

Related Record Type Details


					K1YX059ML1

APRICITABINE

ENANTIOMER -> RACEMATE

Amount:

Details

SMILES

InChI

DescriptionSources: 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

Originator

Approval Year

Targets

Conditions

Approved Use

Cmax

AUC

T1/2

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

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

C_max

T_1/2

Drug as perpetrator