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Details

Stereochemistry ABSOLUTE
Molecular Formula C10H11ClN5O6P
Molecular Weight 363.651
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TOCLADESINE

SMILES

NC1=NC=NC2=C1N=C(Cl)N2[C@@H]3O[C@@H]4COP(O)(=O)O[C@H]4[C@H]3O

InChI

InChIKey=CLLFEJLEDNXZNR-UUOKFMHZSA-N
InChI=1S/C10H11ClN5O6P/c11-10-15-4-7(12)13-2-14-8(4)16(10)9-5(17)6-3(21-9)1-20-23(18,19)22-6/h2-3,5-6,9,17H,1H2,(H,18,19)(H2,12,13,14)/t3-,5-,6-,9-/m1/s1

HIDE SMILES / InChI

Molecular Formula C10H11ClN5O6P
Molecular Weight 363.651
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

8-Chloroadenosine-3',5'-cyclic-monophosphate (8-Cl-cAMP), an analog of c-AMP, is a novel antineoplastic agent. It has been shown to be effective against different human cancer cell lines modulating the cellular signal transduction pathway, thereby causing growth inhibition, cell differentiation, and apoptosis. 8-Cl-cAMP preferentially binds to the R2 subunit of protein kinase A (PKA) and induces rapid R2 up-regulation and eventual R1 subunit down-regulation. It has potent inhibitory effects on a wide variety of human cancer cell lines, with an IC50 ranging from 0.1 to 20 uM. The IC50 falls with the length of drug exposure. It can suppress c-myc and c-ras proto-oncogenes in vitro and in vivo. It was shown that 8-Cl-cAMP induces cell growth inhibition through AMP-activated protein kinase (AMPK) activation with p38 MAPK acting downstream of AMPK in this signaling pathway. 8-Cl-cAMP induced apoptosis, apparently through activation of the p38 MAPK pathway by inducing progressive phosphorylation of the p38 mitogen-activated protein kinase (MAPK), via activation of AMPK by its metabolite 8-Cl-adenosine. 8-Cl-cAMP does not significantly inhibit the growth of NIH 3T3 cells, rat kidney fibroblasts, mammary epithelial cells, or peripheral blood lymphocytes, nor does it inhibit the growth of parental cells whose progeny have been transformed. Such selectivity makes it an attractive candidate for cancer therapy suggesting that it should not cause the toxicity of conventional cytotoxic agents but should inhibit tumor growth. 8-Cl-cAMP has been evaluated in phase I/II clinical trials.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Q15759|||Q2XNF2
Gene ID: 5600.0
Gene Symbol: MAPK11
Target Organism: Homo sapiens (Human)
Target ID: P53778
Gene ID: 6300.0
Gene Symbol: MAPK12
Target Organism: Homo sapiens (Human)
Target ID: O15264
Gene ID: 5603.0
Gene Symbol: MAPK13
Target Organism: Homo sapiens (Human)
Target ID: Q16539|||Q8TDX0
Gene ID: 1432.0
Gene Symbol: MAPK14
Target Organism: Homo sapiens (Human)
Conditions

Conditions

Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 1.4581 uM]
Drug as victim
PubMed

PubMed

TitleDatePubMed
Synthesis and antitumor and antiviral activities of a series of 1-beta-D-ribofuranosyl-5-halocytosine (5-halocytidine) cyclic 3',5'-monophosphates.
1985 Apr
The mechanism of 8-Cl-cAMP action.
1998 Sep
Inhibition of B16 mouse melanoma cell growth and induction of apoptotic cell death with 8-chloroadenosine-3',5'-monophosphate and tiazofurin.
2004 Dec
Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides.
2009 Apr 2
Involvement of AMP-activated protein kinase and p38 mitogen-activated protein kinase in 8-Cl-cAMP-induced growth inhibition.
2009 Jan
Patents

Sample Use Guides

8-Cl-cAMP (TOCLADESINE) was initially given in a 1-month cycle by constant infusion at 0.005 mg/kg/h for 21 days, followed by 1 week of rest. The dose was escalated to 0.045 mg/kg/h, but hypercalcemia became the dose-limiting toxicity. The length of drug administration was, therefore, reduced to 5 days per week for the first 3 weeks of the cycle, but it was not possible to increase the drug dose without producing hypercalcemia
Route of Administration: Intravenous
In the in vitro chromosome cytogenetic assay (CA), 8-chloro-3',5' cyclic adenosine monophosphate (8-Cl-cAMP) (in all respective doses; 1.5 and 15 uM) induced mitotic inhibition and premature centromere separation (PCS) but no chromosomal damage in cultured human peripheral blood lymphocytes.
Substance Class Chemical
Created
by admin
on Sat Dec 16 17:40:35 UTC 2023
Edited
by admin
on Sat Dec 16 17:40:35 UTC 2023
Record UNII
BQ94Z7E5OR
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TOCLADESINE
INN   USAN  
USAN   INN  
Official Name English
8-CHLORO CYCLIC AMP
Common Name English
8-CL-CAMP
Code English
ICN-1256
Code English
NSC-284751
Code English
(4AR,6R,7R,7AS)-6-(6-AMINO-8-CHLORO-PURIN-9-YL)-2-OXO-TETRAHYDRO-2LAMBDA*5*-FURO(3,2-D)(1,3,2)DIOXAPHOSPHININE-2,7-DIOL
Systematic Name English
tocladesine [INN]
Common Name English
TOCLADESINE [USAN]
Common Name English
8-CHLORO-CYCLIC ADENOSINE 3',5'-MONOPHOSPHATE
Common Name English
ADENAZOLE
Common Name English
8-CHLOROADENOSINE-CYCLIC-3',5'-MONOPHOSPHATE
Common Name English
NSC-614491
Code English
8-CHLOROADENOSINE 3',5'-CYCLIC MONOPHOSPHATE
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1934
Created by admin on Sat Dec 16 17:40:35 UTC 2023 , Edited by admin on Sat Dec 16 17:40:35 UTC 2023
NCI_THESAURUS C1556
Created by admin on Sat Dec 16 17:40:35 UTC 2023 , Edited by admin on Sat Dec 16 17:40:35 UTC 2023
Code System Code Type Description
NSC
284751
Created by admin on Sat Dec 16 17:40:35 UTC 2023 , Edited by admin on Sat Dec 16 17:40:35 UTC 2023
PRIMARY
USAN
KK-53
Created by admin on Sat Dec 16 17:40:35 UTC 2023 , Edited by admin on Sat Dec 16 17:40:35 UTC 2023
PRIMARY
EPA CompTox
DTXSID101024678
Created by admin on Sat Dec 16 17:40:35 UTC 2023 , Edited by admin on Sat Dec 16 17:40:35 UTC 2023
PRIMARY
NCI_THESAURUS
C2571
Created by admin on Sat Dec 16 17:40:35 UTC 2023 , Edited by admin on Sat Dec 16 17:40:35 UTC 2023
PRIMARY
CAS
41941-56-4
Created by admin on Sat Dec 16 17:40:35 UTC 2023 , Edited by admin on Sat Dec 16 17:40:35 UTC 2023
PRIMARY
DRUG BANK
DB13046
Created by admin on Sat Dec 16 17:40:35 UTC 2023 , Edited by admin on Sat Dec 16 17:40:35 UTC 2023
PRIMARY
ChEMBL
CHEMBL2107085
Created by admin on Sat Dec 16 17:40:35 UTC 2023 , Edited by admin on Sat Dec 16 17:40:35 UTC 2023
PRIMARY
FDA UNII
BQ94Z7E5OR
Created by admin on Sat Dec 16 17:40:35 UTC 2023 , Edited by admin on Sat Dec 16 17:40:35 UTC 2023
PRIMARY
INN
7842
Created by admin on Sat Dec 16 17:40:35 UTC 2023 , Edited by admin on Sat Dec 16 17:40:35 UTC 2023
PRIMARY
SMS_ID
300000034450
Created by admin on Sat Dec 16 17:40:35 UTC 2023 , Edited by admin on Sat Dec 16 17:40:35 UTC 2023
PRIMARY
NSC
614491
Created by admin on Sat Dec 16 17:40:35 UTC 2023 , Edited by admin on Sat Dec 16 17:40:35 UTC 2023
PRIMARY
PUBCHEM
100299
Created by admin on Sat Dec 16 17:40:35 UTC 2023 , Edited by admin on Sat Dec 16 17:40:35 UTC 2023
PRIMARY
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