8-CHLOROADENOSINE

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H12ClN5O4
Molecular Weight	301.686
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC=NC2=C1N=C(Cl)N2[C@@H]3O[C@H](CO)[C@@H](O)[C@H]3O

InChI

InChIKey=MHDPPLULTMGBSI-UUOKFMHZSA-N

InChI=1S/C10H12ClN5O4/c11-10-15-4-7(12)13-2-14-8(4)16(10)9-6(19)5(18)3(1-17)20-9/h2-3,5-6,9,17-19H,1H2,(H2,12,13,14)/t3-,5-,6-,9-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17168705 | https://www.ncbi.nlm.nih.gov/pubmed/11454694 | https://www.ncbi.nlm.nih.gov/pubmed/21821695

8-chloroadenosine (8-Cl-Ado) is a ribonucleoside analog. The mechanism of its action remains poorly understood, however, it is known that the drug inhibits RNA synthesis. It has significant cytotoxic activity against lymphoid and myeloid malignant cells. The nucleoside analog 8-Cl-Ado is phosphorylated into its cytotoxic triphosphate 8-Cl-ATP. The accumulation of the cytotoxic metabolite results in a parallel decrease of the ATP cellular pools. 8-Cl-Ado gets incorporated into RNA during transcription, hindering this process. In addition, this triphosphate inhibits ATP-dependent poly(A) tail synthesis, and, as a consequence, mRNA processing is inhibited, resulting in vitro cytotoxicity in several solid and hematological malignancies. This agent is currently in clinical trials for the treatment of chronic lymphocytic leukemia and acute myeloid leukemia.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
AMP-activated protein kinase, AMPK 17 Target ID: CHEMBL2096907 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24628795 \| https://www.ncbi.nlm.nih.gov/pubmed/26313261	Activator 1447
ATP synthase subunit beta, mitochondrial 21 Target ID: CHEMBL2062350 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19477165	Inhibitor 8504
actin filament polymerization 1 Target ID: GO:0030041 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16844099	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acute myeloid leukemia 141 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17168705	Primary		Phase II 1147	Unknown Approved Use Unknown
Chronic lymphocytic leukemia 59 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17168705	Primary		Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
275 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/37897709/	100 mg/m² 1 times / day multiple, intravenous dose: 100 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		8-CL-ADO plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00BYW6	https://www.1pchem.com/search?query=1P00BYW6
AK Scientific	9578AJ	https://aksci.com/item_detail.php?cat=9578AJ
Alfa Chemistry	ACM34408145	http://www.alfa-chemistry.com/search.aspx?q=ACM34408145
Angene	AGN-PC-0O94SH	http://www.angenechemical.com/productshow/AGN-PC-0O94SH.html
AstaTech	C15630	http://astatechinc.com/CPSResult.php?CRNO=C15630
BioSynth	W-202410	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/W-202410
BLD Pharm	BD20339	http://www.bldpharm.com/search/Search.html?keyword=BD20339
BOC Sciences	34408-14-5	http://www.bocsci.com/description.asp?cas=34408-14-5
Combi-Blocks	QV-1749	http://www.combi-blocks.com/cgi-bin/find.cgi?QV-1749
eMolecules	1933185	https://orderbb.emolecules.com/search/#?query=1933185
eMolecules	313079316	https://orderbb.emolecules.com/search/#?query=313079316
Fluorochem	516461	http://www.fluorochem.co.uk/Products/Product?code=516461
Lab Network	LN03242824	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN03242824
MolPort	MolPort-002-054-511	https://www.molport.com/shop/molecule-link/MolPort-002-054-511
MolPort	MolPort-046-162-806	https://www.molport.com/shop/molecule-link/MolPort-046-162-806
MolPort	MolPort-047-151-235	https://www.molport.com/shop/molecule-link/MolPort-047-151-235
MuseChem	I000117	https://www.musechem.com/product/I000117.html
Tetrahedron	TS74726	http://www.thsci.com/search.do?q=TS74726
TimTec	ST075649	http://www.echemstore.com/catalogsearch/result/?q=ST075649
Tocris	4436	https://www.tocris.com/search.php?Type=QuickSearch&Value=4436

PubMed

Title	Date	PubMed
Anti-cowpox virus activities of certain adenosine analogs, arabinofuranosyl nucleosides, and 2'-fluoro-arabinofuranosyl nucleosides.	2004	15043161
8-Cl-adenosine-induced inhibition of colorectal cancer growth in vitro and in vivo.	2001-02-24	11191111
Activation of Na(+)- and Ca(2+)-dependent Mg(2+) extrusion by alpha(1)- and beta-adrenergic agonists in rat liver cells.	2000-11	11052991
Determination of pharmacokinetics of 8-chloroadenosine and its two major metabolites in dogs by high-performance liquid chromatography.	2000-09-15	11076086
Site-selective 8-chloroadenosine 3',5'-cyclic monophosphate inhibits transformation and transforming growth factor alpha production in Ki-ras-transformed rat fibroblasts.	1989-01-02	2536620

Patents

Sample Use Guides

In Vivo Use Guide

A Phase I Study of 8-Chloro-Adenosine in Previously Treated Patients With Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma: Starting dose 45 mg/m2 intravenous over 1 hr daily for 5 days every 4 weeks

Route of Administration: Intravenous

In Vitro Use Guide

8-chloroadenosine was effective against clear cell renal cell carcinoma cell viability in vitro, with IC50 ranging from 2 μM in the most sensitive CAKI-1 to 36 μM in the most resistant RXF-393.

Name

Type

Language

ADENOSINE, 8-CHLORO-

Preferred Name

English

8-CHLOROADENOSINE

Systematic Name

English

NSC-354258

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1556