OT-82

OT-82 is a potent, selective and orally active inhibitor of NAMPT. OT-82 is selectively toxic to cells of hematopoietic origin and induces cell death in a NAD+ dependent manner. OT-82 is a promising antineoplastic agent for the study of hematological malignancies[1].

Research Areas >> Cancer

Signaling Pathways >> Apoptosis >> Caspase

Signaling Pathways >> Metabolic Enzyme/Protease >> Nampt

IC50: Nampt[1]

OT-82 (0.0001-10 μM; 72 hours) demonstrates tissue-selective (HP vs non-HP) cytotoxicity. It is against HP cell lines MV4–11, U937, RS4;11, HEL92.1.7 and PER485 cell growth with IC50 values of 2.11 nM, 2.70 nM, 1.05 nM and 1.36 nM, respectively. It also against nonHP cell lines MCF-7, U87, HT29, and H1299 cell growth with IC50 values of 37.92 nM, 29.52 nM, 15.67 nM and 7.95 nM , respectively[1]. OT-82 demonstrates cancer-selective (tumor vs normal) cytotoxicity. It more sensitive to BMMNC from leukemia patients, the IC50 values are 31 nM and 7.10 nM for AML and ALL donors, respectively. The IC50 value is 62.69 nM for BMMNC from healthy donors[1]. OT-82 (0.001-10 μM; 48 hours) inhibits recombinant NAMPT activity and causes dose-dependent reductions in cellular NAD and ATP concentrations in MV4–11 cells[1]. OT-82 (0.01-100 nM; 48 hours) results in activation of caspase-3, an increase in the proportion of cells with sub-G1 DNA content, and depolarization of the mitochondrial membrane in MV4–11 cells[1]. Cell Viability Assay[1] Cell Line: HP cell lines (MV4–11, U937, RS4;11, HEL92.1.7, PER485) Non-HP cell lines (MCF-7, U87, HT29, H1299) Concentration: 0.0001 μM-10 μM Incubation Time: 72 hours Result: Was against human cell lines derived from hematological malignancies (HP) with IC50 values ranging from 1.10 nM to 5.86 nM, and was against non-HP cancers with IC50 ranging from 1.10 nM to 37.92 nM[1]. Apoptosis Analysis[1] Cell Line: MV4–11 cells Concentration: 0.01-100 nM Incubation Time: 48 hours Result: Exhibited hallmarks of apoptotic cell death

OT-82 (oral gavage; 20 or 40 mg/kg; 3 weeks) treatment increases survival to 100% and 56% at 40 or 20 mg/kg, respectively after treatment discontinuation in SC xenograft model of Burkitt's lymphoma[1]. Animal Model: SC xenograft model of Burkitt's lymphoma in SCID mice[1] Dosage: 20 or 40 mg/kg Administration: oral gavage; 3 weeks Result: Potently inhibited tumor growth of multiple myeloma mouse model.

[1]. Korotchkina L, et al. OT-82, a novel anticancer drug candidate that targets the strong dependence of hematological malignancies on NAD biosynthesis.Leukemia. 2020 Jan 2.