Daporinad (FK866)

Catalog No.S2799 Batch:S279904

Technical Data

Formula	C₂₄H₂₉N₃O₂
Molecular Weight	391.51	CAS No.	658084-64-1
Solubility (25°C)*	In vitro	DMSO	78 mg/mL (199.22 mM)
		Ethanol	78 mg/mL (199.22 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

Daporinad (FK866) effectively inhibits nicotinamide phosphoribosyltransferase (NMPRTase; Nampt) with IC50 of 0.09 nM in a cell-free assay. Daporinad (FK866, APO866) triggers autophagy. Phase 1/2.

Targets

NMPRTase ^[5]
(Cell-free assay)

0.4 nM(Ki)

In vitro

APO866 at low concentrations ranging from 0.09-27 nM induces dose-dependent cytotoxicity in 41 hematologic malignant cells including acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL], mantle cell lymphoma [MCL], chronic lymphocytic leukemia [CLL], and T-cell lymphoma. APO866 at low concentrations ranging from 0-10 nM induces cell death, this effect is independent of caspase activation but is associated with depolarization of mitochondrial membrane. APO866 at concentrations ranging from 0-10 nM dose-dependently induces depletion of intracellular NAD and ATP contents and cell death in various hematologic cancer cells. ^[1] APO866 at concentration of 10 nM inhibits PBEF-induced secretion of MMP-3, CCL2, and CXCL8 in HFFF2 cells. ^[2]

In vivo

APO866 administered intraperitoneally at dose of 20 mg/kg twice a day for 4 days, repeat weekly over 3 weeks, prevents and abrogats tumor growth in C.B.-17 SCID mice xenograft models of human AML, lymphoblastic lymphoma, and leukemia. ^[1] APO866 at dose of 0.12 mg/kg/hour prevents joint destruction and leukocyte infiltration through inhibition of PBEF in mice with CIA. ^[2]

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines 41 hematologic malignant cell lines Concentrations 0 - 10 nM Incubation Time 72 hours or 96 hours Method For MTT assays, 0.5 × 10⁶ cells/mL is plated in triplicate on 96-well plates. APO866 (0.01 nM-100 nM) is added in 50 μL of culture medium, with culture medium alone serving as control. After 72 or 96 hours of incubation, 15 μL of dye solution is added to each well and cells are incubated for an additional 4 hours. Stop solution (100 μL/well) is added for 1 hour and the absorbance is read at 570 nm on a spectrophotometer. For trypan blue dye exclusion staining, 0.5 × 10⁵ cells/well is grown in 6-well plates with 1 mL media in the absence or presence of APO866 for 96 hours. Cells from each sample are incubated with 10 μL trypan blue solution (at a 1:1 ratio [vol/vol] for 1 minute). Cell survival is determined by calculating proportion of live (unstained) cells.
Animal Study:^{^[1]}	Animal Models C.B.-17 SCID mice xenograft models of human AML, lymphoblastic lymphoma, and leukemia. Dosages 20 mg/kg Administration administered intraperitoneally twice a day for 4 days, repeated weekly over 3 weeks

Cell Assay:^{^[1]}

Cell lines
41 hematologic malignant cell lines
Concentrations
0 - 10 nM
Incubation Time
72 hours or 96 hours
Method
For MTT assays, 0.5 × 10⁶ cells/mL is plated in triplicate on 96-well plates. APO866 (0.01 nM-100 nM) is added in 50 μL of culture medium, with culture medium alone serving as control. After 72 or 96 hours of incubation, 15 μL of dye solution is added to each well and cells are incubated for an additional 4 hours. Stop solution (100 μL/well) is added for 1 hour and the absorbance is read at 570 nm on a spectrophotometer. For trypan blue dye exclusion staining, 0.5 × 10⁵ cells/well is grown in 6-well plates with 1 mL media in the absence or presence of APO866 for 96 hours. Cells from each sample are incubated with 10 μL trypan blue solution (at a 1:1 ratio [vol/vol] for 1 minute). Cell survival is determined by calculating proportion of live (unstained) cells.

Animal Study:^{^[1]}

Animal Models
C.B.-17 SCID mice xenograft models of human AML, lymphoblastic lymphoma, and leukemia.
Dosages
20 mg/kg
Administration
administered intraperitoneally twice a day for 4 days, repeated weekly over 3 weeks

References

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Customer Product Validation

: Data from [Data independently produced by Mol Endocrinol, 2014, 28(3), 395-405]

: Data from [Data independently produced by , , Drug Des Devel Ther, 2015, 9: 1511-54]

: Data from [Data independently produced by , , Cancer Lett, 2016, 379(1):1-11.]

: Data from [Data independently produced by , , Cell Physiol Biochem, 2018, 49(6):2463-2482]

Selleck's Daporinad (FK866) has been cited by 65 publications

Integration of 3D bioprinting and multi-algorithm machine learning identified glioma susceptibilities and microenvironment characteristics [ Cell Discov, 2024, 10(1):39]	PubMed: 38594259
Decreased liver B vitamin-related enzymes as a metabolic hallmark of cancer cachexia [ Nat Commun, 2023, 14(1):6246]	PubMed: 37803016
Decreased liver B vitamin-related enzymes as a metabolic hallmark of cancer cachexia [ Nat Commun, 2023, 14(1):6246]	PubMed: 37803016
NAD+ Metabolism Generates a Metabolic Vulnerability in Endocrine-Resistant Metastatic Breast Tumors in Females [ Endocrinology, 2023, 164(6)bqad073]	PubMed: 37170651
Improving lysosomal ferroptosis with NMN administration protects against heart failure [ Life Sci Alliance, 2023, 6(12)e202302116]	PubMed: 37793777
Improving lysosomal ferroptosis with NMN administration protects against heart failure [ Life Sci Alliance, 2023, 6(12)e202302116]	PubMed: 37793777
DePARylation is critical for S phase progression and cell survival [ bioRxiv, 2023, 2023.07.31.551317]	PubMed: 37577639
DePARylation is critical for S phase progression and cell survival [ bioRxiv, 2023, 2023.07.31.551317]	PubMed: 37577639
Discovery of small-molecule activators of nicotinamide phosphoribosyltransferase (NAMPT) and their preclinical neuroprotective activity [ Cell Res, 2022, 10.1038/s41422-022-00651-9]	PubMed: 35459935
secDrug: a pipeline to discover novel drug combinations to kill drug-resistant multiple myeloma cells using a greedy set cover algorithm and single-cell multi-omics [ Blood Cancer J, 2022, 12(3):39]	PubMed: 35264575

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SHIPPING AND STORAGE
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