Uzansertib (INCB053914)

Catalog No.S8800 Batch:S880001

Technical Data

Formula	C₂₆H₂₆F₃N₅O₃.H₃O₄P
Molecular Weight	611.51	CAS No.	2088852-47-3
Solubility (25°C)*	In vitro	DMSO	50 mg/mL (81.76 mM)


* <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	Uzansertib (INCB053914) is a novel, ATP-competitive, small molecule, pan-inhibitor of PIM kinases with IC50 values of 0.24 nM, 30 nM and 0.12 nM for PIM1, PIM2 and PIM3 respectively in biochemical assays.
In vitro	INCB053914 potently inhibits the activities of all three PIM isozymes with half maximal inhibitory concentration (IC50) values in the order of PIM1 ≈ PIM3 < PIM2. It is highly selective against a panel of more than 50 kinases (>475-fold selectivity), except for RSK2 for which INCB053914 has modest potency (IC50 = 7.1 μM). No kinase other than Per-Arnt-Sim (PAS) kinase is significantly inhibited by INCB053914 (100 nM)^[1]. In cell proliferation assays, INCB053914 is active as a single agent in the majority of cell lines derived from different hematological malignancies, including MM, AML, DLBCL, MCL and T-ALL, with IC50 values ranging from 3-300 nM. INCB053914 synergizes with a variety of cytotoxic and targeted agents, reducing the viability of a panel of hematological tumor cell lines^[2].
In vivo	In vivo, single-agent INCB053914 inhibits Bcl-2-associated death promoter protein phosphorylation and dose-dependently inhibited tumor growth in acute myeloid leukemia and multiple myeloma xenografts^[2]. INCB053914 inhibits tumor growth in a dose-dependent manner in mice bearing MOLM-16 (AML) or KMS-12-BM (MM) tumors. A pharmacokinetic analysis of INCB053914 plasma concentrations up to 16 hours post oral administration in MOLM-16 and KMS-12-BM tumor-bearing mice suggests dose proportionality^[1].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines MOLM-16 (AML), Pfeiffer (DLBCL), KMS-12-PE (MM), and KMS-12-BM (MM) cells Concentrations 0-1 μM Incubation Time 2 h Method 10⁶ MOLM-16 (AML), Pfeiffer (DLBCL), KMS-12-PE (MM), and KMS-12-BM (MM) cells are incubated with INCB053914 at concentrations ranging from 0 (phosphate-buffered saline [PBS]) to 1 μM for 2 hours in RPMI medium. Cells are centrifuged at 1,000 rpm for 10 minutes and lysed with 1× lysis buffer supplemented with 1 mM phenylmethane sulfonyl fluoride and proteinase inhibitor cocktail. Cell lysates are stored at -80°C before determining phosphoprotein and PIM2 levels by Western blotting.
Animal Study:^{^[1]}	Animal Models Human MOLM-16 (AML) and KMS-12-BM (MM) xenografts established in SCID mice Dosages 0-100 mg/kg Administration by oral gavage

Cell Assay:^{^[1]}

Cell lines
MOLM-16 (AML), Pfeiffer (DLBCL), KMS-12-PE (MM), and KMS-12-BM (MM) cells
Concentrations
0-1 μM
Incubation Time
2 h
Method
10⁶ MOLM-16 (AML), Pfeiffer (DLBCL), KMS-12-PE (MM), and KMS-12-BM (MM) cells are incubated with INCB053914 at concentrations ranging from 0 (phosphate-buffered saline [PBS]) to 1 μM for 2 hours in RPMI medium. Cells are centrifuged at 1,000 rpm for 10 minutes and lysed with 1× lysis buffer supplemented with 1 mM phenylmethane sulfonyl fluoride and proteinase inhibitor cocktail. Cell lysates are stored at -80°C before determining phosphoprotein and PIM2 levels by Western blotting.

Animal Study:^{^[1]}

Animal Models
Human MOLM-16 (AML) and KMS-12-BM (MM) xenografts established in SCID mice
Dosages
0-100 mg/kg
Administration
by oral gavage

References

Selleck's Uzansertib (INCB053914) has been cited by 2 publications

Human papillomavirus insertions identify the PIM family of serine/threonine kinases as targetable driver genes in head and neck squamous cell carcinoma. [ Cancer Lett, 2020, 476:23-33]	PubMed: 31958486
RNA-Seq analysis reveals that spring viraemia of carp virus induces a broad spectrum of PIM kinases in zebrafish kidney that promote viral entry. [ Fish Shellfish Immunol, 2020, 99:86-98]	PubMed: 32004617

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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