INCB18424

Biological Activity

Ruxolitinib (INCB018424) is a first-in-class, potent and selective JAK1/2 inhibitor with an IC50 of 3.3 nM/2.8 nM. It is 130-fold more potent and selective for JAK1 and JAK2 compared to JAK3. In Ba/F3 and HEL cells, INCB018424 potently and selectively inhibited JAK2V617F-mediated signaling and cell proliferation.INCB018424 significantly increased apoptosis in Ba/F3 cells in a dose-dependent manner. In Ba/F3 cells, INCB018424 (64 nM) caused a doubling of mitochondrial depolarized cells.

Product Citations

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  Cell Death Discov. 2024 Aug 29;10(1):389.

  CTDSPL2 promotes the progression of non-small lung cancer through PI3K/AKT signaling via JAK1
  INCB18424 purchased from AbMole

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  Nat Commun. 2023 Nov 27;14(1):7783.

  Local H2 release remodels senescence microenvironment for improved repair of injured bone
  INCB18424 purchased from AbMole

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  FASEB J. 2023 Feb;37(2):e22693.

  ANGPTL4 inhibits granulosa cell proliferation in polycystic ovary syndrome by EGFR/JAK1/STAT3‐mediated induction of p21
  INCB18424 purchased from AbMole

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  Front Immunol. 2022 May 23;13:866638.

  A Novel STAT3 Gain-of-Function Mutation in Fatal Infancy-Onset Interstitial Lung Disease
  INCB18424 purchased from AbMole

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  BMC Biol. 2021 May 20;19(1):108.

  Very long intergenic non-coding (vlinc) RNAs directly regulate multiple genes in cis and trans
  INCB18424 purchased from AbMole

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  Blood Adv. 2020 Jul 14;4(13):3000-3010.

  Inflammation-driven activation of JAK/STAT signaling reversibly accelerates acute myeloid leukemia in vitro
  INCB18424 purchased from AbMole

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  J Virol. 2020 Feb 14;94(5):e01791-19.

  Targeting Kaposi's Sarcoma-Associated Herpesvirus ORF21 Tyrosine Kinase and Viral Lytic Reactivation by Tyrosine Kinase Inhibitors Approved for Clinical Use
  INCB18424 purchased from AbMole

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  Patent. US10335380B2 2019 Jul 02.

  Patent. US10335380B2
  INCB18424 purchased from AbMole

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  Patent. JP6479818B2 2019 Mar 06.

  Patent. JP6479818B2
  INCB18424 purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Leukemia (2013). Figure 2. INCB18424
	Method	MTS assay
	Cell Lines	leukemia cells
	Concentrations	1 μM
	Incubation Time	48 h
	Results	INCB18424 showed a significantly better inhibitory effect than TG101209 at concentrations below 1 μM. Both inhibitors also promoted apoptosis (Figure 2b) and delayed cell cycle progression (Figure 2c) of the AEtr leukemia cell line.

	Source	Leukemia (2013). Figure 1. INCB18424
	Method	CFU assays
	Cell Lines	AML1–ETO- and AE9a-transformed cells
	Concentrations	150, 300, 600, 1200 nM
	Incubation Time	36 h
	Results	Similar to the shRNA results, both inhibitors reduced the colony-forming ability of the transformed cells in a dose-dependent manner

Protocol (for reference only)

Cell Experiment
Cell lines	Ba/F3-EpoR-JAK2V617F and HEL cell lines
Preparation method	Cell proliferation assay. Cells were seeded at 2000/well of white bottom 96-well plates, treated with compounds from DMSO stocks (0.2% final DMSO concentration), and incubated for 48 hours at 37°C with 5% CO2. Viability was measured by cellular ATP determination using the Cell-Titer Glo (Promega) luciferase reagent or viable cell counting. Values were transformed to percent inhibition relative to vehicle control, and IC50 curves were fitted according to nonlinear regression analysis of the data using PRISM GraphPad.
Concentrations	0~10 µ M
Incubation time	48 h

Animal Experiment
Animal models	myeloproliferative neoplasm mouse model
Formulation	5% dimethyl acetamide, 0.5% methyl cellulose
Dosages	180mg/kg began within 24 hours of cell inoculation, twice daily
Administration	oral gavage

Chemical Information

Molecular Weight	306.37
Formula	C17H18N6
CAS Number	941678-49-5
Solubility (25°C)	DMSO 60 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

References

[1] Chase A, et al. Haematologica. Ruxolitinib as potential targeted therapy for patients with JAK2 rearrangements.

[2] Mascarenhas J, et al. Curr Med Chem. Biology and Clinical Management of Myeloproliferative Neoplasms and Development of the JAK Inhibitor Ruxolitinib.

[3] Eghtedar A, et al. Blood. Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia.

[4] Harrison C, et al. N Engl J Med. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis.