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Details

Stereochemistry ABSOLUTE
Molecular Formula C10H15ClN5O13P3
Molecular Weight 541.626
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of 8-Chloro-ATP

SMILES

NC1=C2N=C(Cl)N([C@@H]3O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]3O)C2=NC=N1

InChI

InChIKey=NXKRKKQPDYYKFT-UUOKFMHZSA-N
InChI=1S/C10H15ClN5O13P3/c11-10-15-4-7(12)13-2-14-8(4)16(10)9-6(18)5(17)3(27-9)1-26-31(22,23)29-32(24,25)28-30(19,20)21/h2-3,5-6,9,17-18H,1H2,(H,22,23)(H,24,25)(H2,12,13,14)(H2,19,20,21)/t3-,5-,6-,9-/m1/s1

HIDE SMILES / InChI
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: p38 MAPK pathway
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

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
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
Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides.
2009 Apr 2
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.
Name Type Language
8-Chloro-ATP
Common Name English
8-Chloroadenosin-5′-triphosphate
Common Name English
8-Chloroadenosine 5′-triphosphate
Common Name English
8-Chloroadenosine 5′-(tetrahydrogen triphosphate)
Common Name English
Code System Code Type Description
FDA UNII
Z846LF5DED
Created by admin on Fri Jul 07 00:55:18 UTC 2023 , Edited by admin on Fri Jul 07 00:55:18 UTC 2023
PRIMARY
PUBCHEM
9984799
Created by admin on Fri Jul 07 00:55:18 UTC 2023 , Edited by admin on Fri Jul 07 00:55:18 UTC 2023
PRIMARY
CAS
185341-71-3
Created by admin on Fri Jul 07 00:55:18 UTC 2023 , Edited by admin on Fri Jul 07 00:55:18 UTC 2023
PRIMARY