INO-1001

• Catalog No.: S1132
• CAS Number: 3544-24-9
• M. F.: C7H8N2O
• M. W.: 136.15122
• Storage: -20°C

SYNONYMS

• IUPAC name: 3-aminobenzamide
• IUPAC Traditional name: benzamide, 3-amino-

DATABASE IDS

• CAS Number: 3544-24-9

PROPERTIES

• Target: PARP
• Salt Data: Free Base
• Solubility: DMSO
• Storage Condition: -20°C

DETAILS

Description (English)

Research Area

• Description: Reperfusion injury, Malignant melanoma

Biological Activity

• Description: INO-1001 is a potent inhibitor of PARP with IC50 of 50 nM and a mediator of oxidant-induced myocyte dysfunction during reperfusion.
• Targets: PARP
• IC50: 50 nM ^[1]
• In Vitro: INO-1001 (>1 μM) leads to more than 95% inhibition of PARP activity without significant cellular toxicity. In addition, INO-1001 significantly sensitizes CHO cells by blocking most of the DNA repair occurring between radiation fractions. ^[1] Inhibition of PARP activity by INO-1001 significantly improves endothelial function by enhancing the acetylcholine-induced, endothelium-dependent, nitric oxide mediated vasorelaxation after exposure with 400 μM H₂O₂. ^[2]
• In Vivo: In a db/db (Lepr_db/db) mouse model, INO-1001 ameliorates diabetes-induced albumin excretion and mesangial expansion, and also decreases diabetes-induced podocyte depletion. ^[3] Treatment with INO-1001 (1.6 mg/kg via intracerebral injection) prevents NAD+ depletion and improves water maze performance after controlled cortical impact (CCI) in mice. ^[4]
• Clinical Trials: INO-1001 is currently in Phase II clinical trials in patients with Acute Myocardial Infarction.

Combination Therapy

• Description: In a mismatch repair (MMR)-deficient xenograft, INO-1001 prior to isolated limb infusion (ILI) significantly increased the efficacy of temozolomide (TMZ) and reduces the increase in tumor volume of advanced extremity malignant melanoma than TMZ-ILI alone. ^[5]

Protocol

• Protocol: Kinase Assay ^[1]
• PARP enzyme activity: PARP activity is measured with a PARP Activity Assay Kit. This method measures relative PARP activity by determining the level of incorporation of ₃H-NAD into trichloroacetic acid (TCA) precipitable material in the presence of sheared genomic DNA, which activates PARP. The reaction mixture is added directly to washed cultures in 12-well culture plates and the reaction is allowed to proceed for 60 minutes at 37 °C before the cells are removed mechanically, transferred to a microcentrifuge tube, and precipitated with ice-cold 5% TCA.
• Protocol: Animal Study ^[3]
• Animal Models: Male db/db (Lepr_db/db) mice.
• Formulation: INO-1001 is dissolved in water.
• Doses: ≤60 mg/kg
• Administration: Administered via p.o.

References

• References: [1] Brock WA, et al. Cancer Lett. 2004, 205(2), 155-160.
• References: [2] Radovits T, et al. Eur J Pharmacol. 2007, 564(1-3), 158-166.
• References: [3] Szabó C, et al. Diabetes. 2006, 55(11), 3004-3012.
• References: [4] Clark RS, et al. J Neurotrauma. 2007, 24(8), 1399-1405.
• References: [5] Toshimitsu H, et al. Ann Surg Oncol. 2010, 17(8), 2247-2254.

REFERENCES

• Toshimitsu H, et al. Ann Surg Oncol. 2010, 17(8), 2247-2254.
• Brock WA, et al. Cancer Lett. 2004, 205(2), 155-160.
• Radovits T, et al. Eur J Pharmacol. 2007, 564(1-3), 158-166.
• Szabó C, et al. Diabetes. 2006, 55(11), 3004-3012.
• Clark RS, et al. J Neurotrauma. 2007, 24(8), 1399-1405.