m-Aminobenzamid

INO-1001 · 3-ABA · 3-AB · PARP-IN-1 · 3-AB, 3-ABA · 3-AMINOBENZAMIDE · M-AMINOBENZAMIDE · 3-amino-benzamid

Identifikatoren & physikalische Daten

CAS No.	3544-24-9
Summenformel	C7H8N2O
Durchschnittliche Molmasse	136,15 g/mol
Monoisotopische Masse	136,06366288 g/mol
SMILES	NC(=O)c1cccc(N)c1
InChIKey	GSCPDZHWVNUUFI-UHFFFAOYSA-N
PubChem CID	1645
ChEMBL	CHEMBL81977
ChEBI	CHEBI:64042
EC No.	222-586-9
DTXSID	DTXSID90188922
Lokaler Name	m-Aminobenzamid

Chemische & physikalische Eigenschaften

XLogP	-0,5
Polarare Oberfläche (TPSA)	69,1
H-Brücken-Donoren	2
H-Brücken-Akzeptoren	2
Frei drehbare Bindungen	1
Schwere Atome	10
Formalladung	0
Komplexität	136
LogP (Verteilungskoeffizient)	log Kow = -0.33
Decomposition	When heated to decomposition it emits toxic fumes of /Nitrogen oxide/.
Schmelzpunkt	115-116 °C115-116 °C (lit.)
Siedepunkt	250.42°C (rough estimate)
Dichte	1.1778 (rough estimate)
Brechungsindex	1.5769 (estimate)
Lagerbedingungen	room temp
Löslichkeit	ethanol: 50 mg/mL, clear, faintly yellowSoluble in dimethylformamide (~30 mg/ml), dimethyl sulfoxide (~30 mg/ml), phosphate buffered saline (pH7.2) (~2 mg/ml), water (25 mg/ml), and ethanol (25 mg/ml).
Aggregatzustand	powder
pKa (Säurekonstante)	16.26±0.50(Predicted)
Farbe	white to off-white
BRN	2802373
Stabilität	Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 1 month.
InChI	1S/C7H8N2O/c8-6-3-1-2-5(4-6)7(9)10/h1-4H,8H2,(H2,9,10)
InChIKey	GSCPDZHWVNUUFI-UHFFFAOYSA-N
SMILES	NC(=O)c1cccc(N)c1
LogP (Verteilungskoeffizient)	-0.330
CAS Datenbank	3544-24-9(CAS DataBase Reference)
NIST chemische Informationen	3-NH2-C6H4CONH2(3544-24-9)

Sicherheit & Vorschriften

GHS-Einstufung	WarningH302 (87%): Harmful if swallowed [Warning Acute toxicity, oral]P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 46 reports by companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Hazard Classes and Categories	Acute Tox. 4 (87%)
Entsorgungsverfahren	SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.
Wechselwirkungen	Chronic irradiation (three times a week) with ultraviolet B light of the skin of hairless mouse Uscd (Hr) strains resulted in the induction of skin tumors after 25 to 41 weeks. Topical applications of 3-aminobenzamide (3AB0.1 or 1 M) after each irradiation significantly shortened the earliest time of onset of tumors to 13 to 25 weeks and increased the number of animals that developed tumors over 41 weeks from 67% without 3AB to 73% and 81% with 0.1 and 1 M 3AB, respectively. ...The poly(ADP-ribosyl)transferase inhibitor, 3-aminobenzamide (3-ABA), reduced morphological evidence of 1,2-dibromo-3-chloropropane (DBCP)-induced DNA damage determined by alkaline elution. The DBCP plasma, kidney, and testis tissue doses determined between 1 and 8 hr after a single intraperitoneal injection were somewhat higher with than without 3-ABA pretreatment. Furthermore, the amount of DBCP metabolites covalently bound to macromolecules was reduced to about 20-30 percent of control, indicating that 3-ABA may have an effect on the formation/detoxication of reactive DBCP metabolites. ...... 3-aminobenzamide (3AB) combined with X-rays was used to evaluate the micronucleus dose-response relationship in /in vitro-irradiated lymphocytes/ blood from 14 individuals. While it is known that 3AB inhibits poly(ADP-ribose) polymerase activity in vitro, ... it also increases the X-ray-induced micronucleus yields. The resulting dose-response relationship varies from subject to subject. ...Gene expression of human immunodeficiency virus type 1 (HIV-1) is induced not only by trans activation mediated through a gene product (tat) encoded by the virus but also by treatment of virus-carrying cells with DNA-damaging agents such as UV light. Employing an artificially constructed DNA in which the chloramphenicol acetyltransferase gene was placed under the control of the HIV-1 long terminal repeat, ... the induction process in HeLa cells /was analyzed/ and ... inhibitors of poly(ADP-ribose) polymerase /including 3-aminobenzamide/ suppressed UV-induced HIV-1 gene expression but not tat-mediated expression. ... Suppression occurs at the posttranscriptional level. These results indicate that HIV-1 gene expression is activated by at least two different mechanisms, one of which involves poly-ADP ribosylation. ...Synergistically enhanced sister chromatid exchange (SCE) frequency by cyclophosphamide (CP) was observed when L1210 lymphoid tumor cells were exposed in vivo to a non-toxic concentration of 3-aminobenzamide (3-AB). Additive effects in SCE induction in vivo were observed when either Ehrlich ascites tumor (EAT) cells or P388 lymphocytic leukemia cells treated with CP were exposed to 3-AB in vivo. 3-AB enhanced the survival time of L1210 tumor bearing BDF1 mice treated with CP. However, the combined CP plus 3-AB treatment did not increase the survival of either EAT BALB/c- or P388 BDF1-tumor bearing mice compared with the effect on survival by CP alone. Therefore the in vivo differential antitumor effect, by CP in conjunction with 3-AB, appears to correlate well with the in vivo differential effect on cytogenetic damage caused by the combined CP plus 3-AB treatment. In the Salmonella typhimurium/mammalian microsome test CP appears to have a dose dependent ability to induce base-pair substitutions in strains TA 100 and TA 1535 and frameshift mutations in strains TA 98 and TA 1537. Both types of mutation were synergistically increased in the presence of 3-AB.
Human Toxicity Excerpts	/ALTERNATIVE and IN VITRO TESTS/ A /human fibroblast/ cell line deficient in DNA ligase I and sensitive to poly(ADP-ribose) inhibitors, 46BR, was used to examine the relationship between DNA ligation and a large stimulation of repair replication that is seen in cells grown in a poly(ADP-ribose) polymerase inhibitor, 3-aminobenzamide (3AB), after exposure to alkylating agents. Repair replication was stimulated at least 10-fold by 3AB in both normal and ligase-deficient cells. Despite increased 3AB toxicity, repair replication in ligase I-deficient cells was unchanged from that in normal cells. This evidence is consistent with previous observations that the enhancement of repair replication by 3AB is not a direct function of DNA break frequencies. The stimulation may instead result from alkylation damage to other cellular organelles that release nucleases that cause additional damage to DNA, which cells attempt to repair./GENOTOXICITY/ ... The effect of 3-aminobenzamide (3AB) in gamma-irradiation induced damage and the subsequent repair of DNA along with the corresponding changes in poly (ADP-ribose) polymerase activity in lymphocytes of patients with cancer of breast and uterine cervix /was studied/. The presence or absence of 3AB prior to gamma-irradiation did not influence the extent of DNA damage. On the other hand, single strand break rejoining in breast cancer cases was found to be slower as compared to that of cervical cancer cases and normal individuals. The relative ADP-ribosylation in the presence of 3AB was much lower in the breast cancer cases as compared to normal but there was no significant change in the cervical cancer cases. Overall the maximum relative ADP-ribosylation was slower in the presence of 3AB. This suggests that the lower activity of poly (ADP-ribose) polymerase in breast cancer cases might delay the first phase of single strand breaks (SSBs) rejoining./GENOTOXICITY/ Effects of 5-hydroxymethyl-2'-deoxyuridine (HmdUrd, a thymidine analog) and 3-aminobenzamide (3AB) on chromosome aberrations in cultured human lymphocytes were studied. The results show that HmdUrd is an effective clastogen in human peripheral lymphocytes. When cells were treated with HmdUrd and 3AB, a synergistic effect on chromatid gaps, breaks and exchanges was found. These findings support the hypotheses that 5-hydroxymethyluracil (HmUra) residues in DNA are formed and then removed by the action of 5-HmUra-DNA glycosylase ... and that 3AB interferes with the completion of DNA repair following HmUra excision.
Non-Human Toxicity Excerpts	/LABORATORY ANIMALS: Acute Exposure/ There have been no previous studies of the effects of poly(ADP-ribose) polymerase (PARP) inhibitors on N-methyl-N-nitrosourea (MNU)-induced cataractogenesis in rats. A single intraperitoneal injection of 70 mg/kg MNU was administered to 15-day-old male and female Sprague-Dawley rats. In Experiment 1, rats were then subcutaneously injected with 1000 mg/kg nicotinamide either once or 3 times at 1-week intervals. In Experiment 2, rats were subcutaneously injected once with 50 mg/kg 3-aminobenzamide. For comparison, the following age-matched controls were included: MNU-untreated nicotinamide-injected rats, MNU-untreated 3-aminobenzamide-injected rats, and MNU-untreated PARP-inhibitor-untreated rats. Rats were examined for lens opacity. At 28 days after MNU injection, 10 to 20 rats per group were sacrificed. In Experiment 1, at 3 days after MNU injection, 10 rats per group were sacrificed for apoptosis and cell proliferation detection. MNU caused lens epithelial cell apoptosis in the germinative zone, as indicated by TUNEL staining. However, regardless of MNU treatment lens epithelial cell proliferation was consistently seen in the germinative zone and sporadically seen in the central zone. At 28 days after MNU, mature cataracts were observed. Nicotinamide significantly accelerated lens opacity and cataractogenesis, as indicated by a cataract index. 3-Aminobenzamide significantly accelerated the development of lens opacity and tended to accelerate cataractogenesis. The PARP inhibitors nicotinamide and 3-aminobenzamide accelerated MNU-induced cataractogenesis./LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Effects of 3-aminobenzamide (ABA) on pancreatic carcinogenesis after initiation by N-nitrosobis(2-oxopropyl)amine (BOP) were investigated in Syrian hamsters. Animals were given BOP at a dose of 70 mg/kg body weight by sc injection and following a 2-week recovery period, were administered basal diet or basal diet containing 0.5, 0.75 and 1.5% ABA for 30 weeks. While the incidences of resultant pancreatic lesions, including hyperplasia, atypical hyperplasia and carcinoma, induced by BOP were not significantly influenced by ABA treatment, the mean numbers of those pancreatic lesions were significantly decreased in a dose-dependent way. The results therefore suggested the possible involvement of poly(ADP-ribosyl)ation in the post-initiation phase of pancreatic carcinogenesis in hamsters./LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ The effects of inhibitors of poly(ADP-ribose)polymerase, 3-aminobenzamide (ABA), luminol and 3-methoxybenzamide (MBA) on the rat liver tumor promotion activity of phenobarbital (PB) were assessed. Fischer 344 male rats were initiated with N-nitrosodiethylamine (200 mg/kg) and placed on either basal diet, diet containing 0.05% PB, diet containing various doses of the inhibitors alone or diet containing 0.05% PB plus various doses of inhibitors for 10 weeks, and then killed. Quantitation of the development of glutathione S-transferase placental form-positive foci revealed that ABA at doses of 2 and 1.5, but not 1%, significantly inhibited the PB promotion activity. Luminol dose-dependently reduced PB promotion at doses of 3 and 6% but exerted no effects at the 1 and 2% levels. MBA also demonstrated a dose-dependent inhibitory influence at doses of 1 and 2%./ALTERNATIVE and IN VITRO TESTS/ Damage of 3T3 fibroblasts as induced by short-term co-cultivation with O2(-)-producing granulocytes, stimulated by 12-O-tetradecanoyl-phorbol-13-acetate (TPA), was compared with that induced by treatment with enzymically generated O2- and with the alkylating agent dimethyl sulfate. ... 3-Aminobenzamide, the most widely used inhibitor of ADP-ribosylation, partially protected target cells from the cytotoxic effects of TPA-stimulated granulocytes, while it enhanced alkylation-induced and O2(-)-induced cytotoxicity. Protection by 3-aminobenzamide in the granulocyte system was apparently not mediated by an inhibition of nuclear poly(ADP-ribosyl)ation. ... The unique effect of 3-aminobenzamide in this system appeared to relate to TPA-induced adhesion of the neutrophils to surfaces. In the presence of 1 mM 3-aminobenzamide, but not of benzamide, the adhesion of stimulated granulocytes to 3T3 monolayer cultures was markedly reduced or even abolished. This effect was also seen in granulocyte preparations depleted of monocytes. Since 3-aminobenzamide at the doses applied does not inhibit TPA-induced superoxide production in isolated granulocytes, its specific anticytotoxic effect appears to result from a dilution of granulocyte-derived damaging agents into the medium. ... Prevention of granulocyte adhesion is likely to reduce tissue damage and carcinogenesis in areas of chronic inflammation./GENOTOXICITY/ In SVM cells, an SV40-transformed line of Indian muntjac fibroblasts, levels of sister-chromatid exchanges are known to be abnormally high after UV-irradiation or alkylation. The SVM line is also known to have a defect in the processing of DNA-strand breaks. Sister-chromatid exchange in other cells is known to be stimulated by the poly(ADP-ribose) transferase inhibitor, 3-aminobenzamide, which also retards DNA-break sealing. Sister-chromatid exchanges in SVM cells are found to be hypersensitive to 3-aminobenzamide, or to nicotinamide deprivation which similarly inhibits poly(ADP-ribosyl)ationDNA-strand breaks are likewise induced by 3-aminobenzamide. Bromodeoxyuridine, needed to detect sister-chromatid exchanges, is more toxic to SVM cells and itself induces sister-chromatid exchanges to a greater extent than it does in normal muntjac cells. ... The mechanism by which BrdU exerts its effects can largely be explained in terms of familiar effects on deoxyribonucleotide pools and DNA integrity. 3-Aminobenzamide, however, induces sister-chromatid exchanges in SVM cells by another mechanism.
Wassergefährdungsklasse (WGK)	3
UN-Transportnummer	3077
Zollcode	29242990
RTECS-Nr.	CU8992000
R-Sätze (R)	36/37/38
Gefahrensymbole	Xi
Sicherheitshinweise (S)	26-36-37/39
Lagerklasse	11 - Combustible Solids
Gefahrstoffdaten	3544-24-9(Hazardous Substances Data)

Anwendungen & Verwendung

Beschreibung

The poly(ADP-ribose) polymerases (PARPs) comprise a family of enzymes which post-translationally modify proteins by poly(ADP-ribosyl)ation. Since some PARPs are activated by DNA strand breaks, PARP signaling has roles in DNA repair, apoptosis, inflammation, and other cellular responses. 3-amino Benzamide is an inhibitor of PARPs (Ki = 1.8 μM). Through its effects on PARPs, 3-amino benzamide causes telomere shortening and stimulates angiogenesis. It has PARP-mediated actions in such diverse diseases as atherosclerosis, neurogenesis, and cancer.

Verwenden

3-Aminobenzamide is used as an endogenous poly-ADP-ribosyltransferase inhibitor. Through its effects on PARPs, 3-amino benzamide causes telomere shortening and stimulates angiogenesis. It displays neuroprotective, anti-necrotic effects.