CARBOXYAMIDOTRIAZOLE

Investigational

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

Structure Search

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)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2152805 | https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=41613

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
calcium-mediated signaling 2 Target ID: GO:0019722 Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=41613	Blocker 537
cell proliferation 28 Target ID: GO:0008283 Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=41613	Inhibitor 8297		1.6 mM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Kidney cancer 10 Sources: https://clinicaltrials.gov/ct2/show/study/NCT00005045	Primary	Phase II 1132	CARBOXYAMIDOTRIAZOLE Approved Use Unknown
Renal cell cancer 7 Sources: https://clinicaltrials.gov/ct2/show/study/NCT00006486	Primary	Phase II 1132	CARBOXYAMIDOTRIAZOLE Approved Use Unknown
Non-small cell lung cancer 206 Sources: https://clinicaltrials.gov/ct2/show/study/NCT00003869	Primary	Phase III 656	CARBOXYAMIDOTRIAZOLE Approved Use Unknown

C_max

Value	Dose	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	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

T_1/2

Value	Dose	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

Sourcing

Vendor/Aggregator	ID	URL
AK Scientific	X7001	https://aksci.com/item_detail.php?cat=X7001
Alfa Chemistry	281674	http://www.alfa-chemistry.com/search.aspx?q=281674
Alfa Chemistry	ACM99519843	http://www.alfa-chemistry.com/search.aspx?q=ACM99519843
Angene	AGN-PC-0WH3OI	http://www.angenechemical.com/productshow/AGN-PC-0WH3OI.html
ApexBio Technology	B7269	https://www.apexbt.com/catalogsearch/result/?q=B7269
AstaTech	76208	http://astatechinc.com/CPSResult.php?CRNO=76208
BLD Pharm	BD42149	http://www.bldpharm.com/search/Search.html?keyword=BD42149
BOC Sciences	99519-84-3	http://www.bocsci.com/description.asp?cas=99519-84-3
Capot Chemical	13343	https://www.capotchem.com/search.do?q=13343
Chem Scene	CS-0006151	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0006151
Chem Scene	CS-0006152	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0006152
ChemShuttle	149096	https://www.chemshuttle.com/catalogsearch/result/?q=149096
Combi-Blocks	QK-4441	http://www.combi-blocks.com/cgi-bin/find.cgi?QK-4441
Debye Scientific	DA-38085	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-38085
Hairui	HR142518	http://www.hairuichem.com/en/product/search.do?q=HR142518
MedChem Express	HY-16125	https://www.medchemexpress.com/search.html?q=HY-16125&ft=&fa=&fp=
MolPort	MolPort-008-155-743	https://www.molport.com/shop/molecule-link/MolPort-008-155-743
MuseChem	M133503	https://www.musechem.com/product/M133503.html
MuseChem	R040348	https://www.musechem.com/product/R040348.html
Princeton BioMolecular Research	PBMR221759	http://www.princetonbio.com/order_online?common_id=PBMR221759
Tetrahedron	TS69960	http://www.thsci.com/search.do?q=TS69960
Tocris	3086	https://www.tocris.com/search.php?Type=QuickSearch&Value=3086
Toronto Research Chemicals	C177775	https://www.trc-canada.com/product-detail/?CatNum=C177775
Toronto Research Chemicals	M330685	https://www.trc-canada.com/product-detail/?CatNum=M330685
eMolecules	748551	https://orderbb.emolecules.com/search/#?query=748551
mcule	MCULE-8784658129	https://mcule.com/MCULE-8784658129/

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	9353347
Tumour angiogenesis: a novel therapeutic target in patients with malignant disease.	2001 Apr	15989502
Vascular endothelial growth factor-A activates Ca2+ -activated K+ channels in human endothelial cells in culture.	2001 Apr	11312104
Protein binding alters the activity of suramin, carboxyamidotriazole, and UCN-01 in an ex vivo rat aortic ring angiogenesis assay.	2001 Jul	11448898
Essential role of calcium in vascular endothelial growth factor A-induced signaling: mechanism of the antiangiogenic effect of carboxyamidotriazole.	2002 Nov	12354692
Gateways to clinical trials.	2003 Nov	14685303
The blocking of capacitative calcium entry by 2-aminoethyl diphenylborate (2-APB) and carboxyamidotriazole (CAI) inhibits proliferation in Hep G2 and Huh-7 human hepatoma cells.	2004 Dec	15488595
A phase I trial of pharmacokinetic modulation of carboxyamidotriazole (CAI) with ketoconazole in patients with advanced cancer.	2004 Nov	15235824
An ex-vivo angiogenesis assay as a screening method for natural compounds and herbal drug preparations.	2004 Oct	15490313
Carboxyamidotriazole-induced inhibition of mitochondrial calcium import blocks capacitative calcium entry and cell proliferation in HEK-293 cells.	2005 Dec 1	16306224
Phase II study of carboxyamidotriazole in patients with advanced renal cell carcinoma refractory to immunotherapy: E4896, an Eastern Cooperative Oncology Group Study.	2005 Dec 1	16222691
Supra-additive growth inhibition by a celecoxib analogue and carboxyamido-triazole is primarily mediated through apoptosis.	2005 May 1	15867384
Gateways to clinical trials.	2007 Oct	18040531
Arachidonic acid-induced Ca2+ entry is involved in early steps of tumor angiogenesis.	2008 Apr	18403634
Anti-inflammatory and analgesic potency of carboxyamidotriazole, a tumorostatic agent.	2008 Apr	18182559
Effects of carboxyamidotriazole on in vitro models of imatinib-resistant chronic myeloid leukemia.	2008 Apr	17924401
Selective sensitivity to carboxyamidotriazole by human tumor cell lines with DNA mismatch repair deficiency.	2008 Jul 15	18464258
Gateways to clinical trials. July-August 2008.	2008 Jul-Aug	18850047
Neurological and neurobehavioral assessment of experimental subarachnoid hemorrhage.	2009 Aug 25	19706182
[Anti-inflammatory and analgesic potency of carboxyamidotriazole, a tumoristatic agent].	2009 Jun	19621516
Antivascular therapy for epithelial ovarian cancer.	2010	20072701
Targeting retinal and choroid neovascularization using the small molecule inhibitor carboxyamidotriazole.	2010 Feb 15	19679174
Multiple roles of protein kinase a in arachidonic acid-mediated Ca2+ entry and tumor-derived human endothelial cell migration.	2010 Nov	20870737

Patents

Sample Use Guides

In Vivo Use Guide

Carboxyamidotriazole at a dose of 250 mg was administered daily.

Route of Administration: Oral

In Vitro Use Guide

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

CARBOXYAMIDOTRIAZOLE

Common Name

English

5-AMINO-1-((3,5-DICHLORO-4-(4-CHLOROBENZOYL)PHENYL)METHYL)-1H-1,2,3-TRIAZOLE-4-CARBOXAMIDE

Systematic Name

English

L 651582

Code

English

CAI

Common Name

English

NSC-609974

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1971