INO-1001

Biological Activity

INO-1001 is a novel poly(ADP-ribose) polymerase (PARP) inhibitor improves cardiac and pulmonary function after crystalloid cardioplegia and extracorporal circulation. The present study tested INO-1001 for its in vivo effect on the chemoresponse of two p53 deficient tumors, human breast cancer MDA-MB-231 and murine mammary carcinoma MCa-K. Doxorubicin was used as the DNA damaging agent and tumor growth delay assay was used as the endpoint. Results showed that INO-1001 was highly effective in enhancing the anti-tumor effects of Doxorubicin for both MDA-MB-231 (EF=1.88) and MCa-K (EF=1.64).

Product Citations

• 

  Bioact Mater. 2022 Feb 9.

  pH and lipase-responsive nanocarrier-mediated dual drug delivery system to treat periodontitis in diabetic rats
  INO-1001 purchased from AbMole

• 

  Cell Commun Signal. 2020 Feb 17;18(1):27.

  mTOR May Interact With PARP-1 to Regulate Visible Light-Induced Parthanatos in Photoreceptors
  INO-1001 purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Exp Gerontol (2007). Figure 2. INO-1001
	Method	i.p.
	Cell Lines	male Lewis rats
	Concentrations	5 mg/kg
	Incubation Time	2 h
	Results	Single dose treatment with the potent PARP-inhibitor INO-1001 notably decreased PAR formation both in the myocardium and the aortic wall.

Protocol

Cell Experiment
Cell lines	cultured podocytes
Preparation method	Apoptosis detection. Apoptotic nuclei of cultured podocytes were detected on paraformaldehyde-fixed cells using DAPI (4′,6-diamidino-2-phenylindole) staining (1 μg/ml) for 10 min. Cells were analyzed under a fluorescence microscope and assessed for chromatin condensation and segregation. Caspase-3 activity was measured in podocyte extracts using EnzCheck Caspase-3 Assay kit (Molecular Probes) following the manufacturer’s protocol. Nuclear extracts were prepared using Transfactor DB Nuclear extraction kit (Clontech BD Bioscience) following the manufacturer’s protocol. Western blotting was performed using NFκB p50 (Santa Cruz Biotechnology) antibody. NFκB p50 nuclear binding assay was performed using TransFactor Colorimetric kit (Clontech BD) according to the manufacturer’s protocol.
Concentrations	200 nmol/l
Incubation time	45 min

Animal Experiment
Animal models	diabetic nephropathy of Leprdb/db mice model
Formulation	sterile water
Dosages	60 mg/kg initiated at 5 weeks of age to around 8 weeks of age
Administration	oral in drinking water

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information

References

[1] Roesner JP, et al. Shock. Therapeutic injection of PARP inhibitor INO-1001 preserves cardiac function in porcine myocardial ischemia and reperfusion without reducing infarct size.

[2] Bedikian AY, et al. Cancer Invest. A phase IB trial of intravenous INO-1001 plus oral temozolomide in subjects with unresectable stage-III or IV melanoma.

[3] Morrow DA, et al. J Thromb Thrombolysis. A randomized, placebo-controlled trial to evaluate the tolerability, safety, pharmacokinetics, and pharmacodynamics of a potent inhibitor of poly(ADP-ribose) polymerase (INO-1001) in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: results of the TIMI 37 trial.

[4] Robert S B Clark, et al. J Neurotrauma. Local administration of the poly(ADP-ribose) polymerase inhibitor INO-1001 prevents NAD+ depletion and improves water maze performance after traumatic brain injury in mice

[5] Mason KA, et al. Invest New Drugs. INO-1001, a novel inhibitor of poly(ADP-ribose) polymerase, enhances tumor response to doxorubicin.

[6] Radovits T, et al. Exp Gerontol. Single dose treatment with PARP-inhibitor INO-1001 improves aging-associated cardiac and vascular dysfunction.

[7] Csaba Szabo, et al. Diabetes. Poly(ADP-ribose) polymerase inhibitors ameliorate nephropathy of type 2 diabetic Leprdb/db mice