OT-82

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

OT-82 是一种强效、选择性和具有口服活性的 NAMPT 的抑制剂。OT-82 对造血源细胞有选择性毒性，以 NAD+依赖方式诱导细胞死亡。OT-82 是一种很有前途的抗肿瘤试剂 (antineoplastic agent)，用于血液系统恶性肿瘤的研究。

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.

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.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 ALLdonors, respectively. The IC50 value is 62.69 nM for BMMNC from healthy donors.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.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.Cell Viability Assay 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.Apoptosis Analysis 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.Animal Model:SC xenograft model of Burkitt's lymphoma in SCID mice Dosage:20 or 40 mg/kg Administration:oral gavage; 3 weeks Result:Potently inhibited tumor growth of multiple myeloma mouse model.

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Metabolic Enzyme/Protease

NAMPT

NAMPT

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1800487-55-1

424.47

C26H21FN4O

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 100 mg/mL (235.59 mM; 超声助溶 )

O=C(NCCCC=1C=NNC1)C=2C=CC(=C(C#CC3=CC=C(F)C=C3)C2)C=4C=CN=CC4

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(-20℃)

With Ice Pack

≥ 2 years