Details
Stereochemistry | ACHIRAL |
Molecular Formula | C17H12Cl3N5O2 |
Molecular Weight | 424.668 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
NC(=O)C1=C(N)N(CC2=CC(Cl)=C(C(=O)C3=CC=C(Cl)C=C3)C(Cl)=C2)N=N1
InChI
InChIKey=WNRZHQBJSXRYJK-UHFFFAOYSA-N
InChI=1S/C17H12Cl3N5O2/c18-10-3-1-9(2-4-10)15(26)13-11(19)5-8(6-12(13)20)7-25-16(21)14(17(22)27)23-24-25/h1-6H,7,21H2,(H2,22,27)
Carboxyamidotriazole (L651582) is a carboxyamide-amino-imidazole compound originally developed as a coccidiostat, an antiprotozoal agent that acts upon Coccidia parasites. Carboxyamidotriazole (L651582) is an orally-active agent with potential antineoplastic activity. Carboxyamidotriazole binds to and inhibits non-voltage-operated Ca2 channels, blocking both Ca2 influx into cells and Ca2 release from intracellular stores and resulting in the disruption of calcium channel-mediated signal transduction and inhibition of vascular endothelial growth factor (VEGF) signaling, endothelial proliferation, and angiogenesis. This agent may also inhibit tumor cell growth, invasion, and metastasis.
CNS Activity
Sources: http://www.tacticaltherapeutics.com/wp-content/uploads/2016/08/Arm-C-ASCO-12-007-Poster-2016-AO-5-19-16.pdf
Curator's Comment: The orotate salt form of carboxyamidotriazole crosses the blood-brain barrier.
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2152805
Curator's Comment: # Merck & Co., Inc.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: GO:0019722 |
|||
Target ID: GO:0008283 |
1.6 mM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | CARBOXYAMIDOTRIAZOLE Approved UseUnknown |
|||
Primary | CARBOXYAMIDOTRIAZOLE Approved UseUnknown |
|||
Primary | CARBOXYAMIDOTRIAZOLE Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1.822 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10485080 |
250 mg/m² 2 times / day multiple, oral dose: 250 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: |
CARBOXYAMIDOTRIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
0.57 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11801543 |
300 mg/m² single, oral dose: 300 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
CARBOXYAMIDOTRIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
0.6 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11801543 |
200 mg/m² single, oral dose: 200 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
CARBOXYAMIDOTRIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
0.17 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11801543 |
75 mg/m² single, oral dose: 75 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
CARBOXYAMIDOTRIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
0.32 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11801543 |
250 mg/m² single, oral dose: 250 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
CARBOXYAMIDOTRIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
0.583 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10485080 |
250 mg/m² 2 times / day multiple, oral dose: 250 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: |
CARBOXYAMIDOTRIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
138.89 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10485080 |
250 mg/m² 2 times / day multiple, oral dose: 250 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: |
CARBOXYAMIDOTRIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
10.6 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11801543 |
300 mg/m² single, oral dose: 300 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
CARBOXYAMIDOTRIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
11 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11801543 |
200 mg/m² single, oral dose: 200 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
CARBOXYAMIDOTRIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
2.7 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11801543 |
75 mg/m² single, oral dose: 75 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
CARBOXYAMIDOTRIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
5.9 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11801543 |
250 mg/m² single, oral dose: 250 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
CARBOXYAMIDOTRIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
52.5 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10485080 |
250 mg/m² 2 times / day multiple, oral dose: 250 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: |
CARBOXYAMIDOTRIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
71 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11801543 |
300 mg/m² single, oral dose: 300 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
CARBOXYAMIDOTRIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
66 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11801543 |
200 mg/m² single, oral dose: 200 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
CARBOXYAMIDOTRIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
89 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11801543 |
75 mg/m² single, oral dose: 75 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
CARBOXYAMIDOTRIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
76 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11801543 |
250 mg/m² single, oral dose: 250 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
CARBOXYAMIDOTRIAZOLE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
PubMed
Title | Date | PubMed |
---|---|---|
Selective inhibition of mitogen-induced transactivation of the HIV long terminal repeat by carboxyamidotriazole. Calcium influx blockade represses HIV-1 transcriptional activation. | 1997 Nov 7 |
|
Dissociation between vasospasm and functional improvement in a murine model of subarachnoid hemorrhage. | 2006 Sep 15 |
|
Gateways to clinical trials. | 2007 Oct |
|
Arachidonic acid-induced Ca2+ entry is involved in early steps of tumor angiogenesis. | 2008 Apr |
|
Selective sensitivity to carboxyamidotriazole by human tumor cell lines with DNA mismatch repair deficiency. | 2008 Jul 15 |
|
Multiple roles of protein kinase a in arachidonic acid-mediated Ca2+ entry and tumor-derived human endothelial cell migration. | 2010 Nov |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16222691
Carboxyamidotriazole at a dose of 250 mg was administered daily.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2152805
The inhibitory effects of carboxyamidotriazole (L651582) on cancer proliferation, adhesion, and motility in vitro and in vivo in a model of ovarian cancer progression were studied. L651582 reversibly inhibited up to 60% of the autocrine motility factor-stimulated tumor cell motility and tumor cell adhesion to tissue culture plastic. Autocrine motility factor-stimulated phosphoinositide metabolism was reduced significantly by treatment of the cells with 3 microM L651582 (P = 0.022). Thymidine incorporation and clonogenic growth of A2058 human melanoma, MDA-MB-231 human breast cancer, OVCAR-3 human ovarian cancer, and 5R-transformed rat embryo fibroblast cell lines were inhibited 60%-80% by 1-10 microM L651582. Intraperitoneal injection of OVCAR-3 cells causes malignant ascites, peritoneal carcinomatosis, and serosal and visceral seeding that, if left untreated, are lethal to nude mice. Intraperitoneal L651582 markedly prolonged survival of nude mice heavily laden with ovarian cancer [mean survival time of treated group divided by mean survival time of control group = 220% (P less than 0.03)].
Name | Type | Language | ||
---|---|---|---|---|
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Code | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
NCI_THESAURUS |
C1971
Created by
admin on Fri Dec 15 15:44:11 GMT 2023 , Edited by admin on Fri Dec 15 15:44:11 GMT 2023
|
||
|
NCI_THESAURUS |
C333
Created by
admin on Fri Dec 15 15:44:11 GMT 2023 , Edited by admin on Fri Dec 15 15:44:11 GMT 2023
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
6ST3ZF52WB
Created by
admin on Fri Dec 15 15:44:11 GMT 2023 , Edited by admin on Fri Dec 15 15:44:11 GMT 2023
|
PRIMARY | |||
|
CARBOXYAMIDOTRIAZOLE
Created by
admin on Fri Dec 15 15:44:11 GMT 2023 , Edited by admin on Fri Dec 15 15:44:11 GMT 2023
|
PRIMARY | |||
|
609974
Created by
admin on Fri Dec 15 15:44:11 GMT 2023 , Edited by admin on Fri Dec 15 15:44:11 GMT 2023
|
PRIMARY | |||
|
100000178003
Created by
admin on Fri Dec 15 15:44:11 GMT 2023 , Edited by admin on Fri Dec 15 15:44:11 GMT 2023
|
PRIMARY | |||
|
108144
Created by
admin on Fri Dec 15 15:44:11 GMT 2023 , Edited by admin on Fri Dec 15 15:44:11 GMT 2023
|
PRIMARY | |||
|
DTXSID40244108
Created by
admin on Fri Dec 15 15:44:11 GMT 2023 , Edited by admin on Fri Dec 15 15:44:11 GMT 2023
|
PRIMARY | |||
|
99519-84-3
Created by
admin on Fri Dec 15 15:44:11 GMT 2023 , Edited by admin on Fri Dec 15 15:44:11 GMT 2023
|
PRIMARY | |||
|
DB11960
Created by
admin on Fri Dec 15 15:44:11 GMT 2023 , Edited by admin on Fri Dec 15 15:44:11 GMT 2023
|
PRIMARY | |||
|
C1141
Created by
admin on Fri Dec 15 15:44:11 GMT 2023 , Edited by admin on Fri Dec 15 15:44:11 GMT 2023
|
PRIMARY |
METABOLITE (PARENT)
SUBSTANCE RECORD