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Chemical Structure| 1334298-90-6 Chemical Structure| 1334298-90-6

Structure of Itacitinib
CAS No.: 1334298-90-6

Chemical Structure| 1334298-90-6

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Itacitinib is an oral selective JAK1 tyrosine kinase inhibitor, which is potential for the treatment of rheumatoid arthritis, myelofibrosis, rheumatoid arthritis and plaque psoriasis.

Synonyms: INCB039110; INCB39110; 1334298-96-2

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Product Details of Itacitinib

CAS No. :1334298-90-6
Formula : C26H23F4N9O
M.W : 553.51
SMILES Code : N#CCC1(N2N=CC(C3=C4C(NC=C4)=NC=N3)=C2)CN(C5CCN(C(C6=CC=NC(C(F)(F)F)=C6F)=O)CC5)C1
Synonyms :
INCB039110; INCB39110; 1334298-96-2
MDL No. :MFCD28579595
InChI Key :KTBSXLIQKWEBRB-UHFFFAOYSA-N
Pubchem ID :53380437

Safety of Itacitinib

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Related Pathways of Itacitinib

epigenetics
RTK
JAK-STAT

Isoform Comparison

Biological Activity

Description
Itacitinib (INCB039110), an oral, selective JAK1 inhibitor, showcases an IC50 of 2 nM for JAK1, demonstrating over 20-fold selectivity against JAK2 and over 100-fold against JAK3 and TYK21].[2].

In Vitro:

Cell Line
Concentration Treated Time Description References
Monocytes 25 μM 1 hour Evaluated the inhibitory effect of ITA on STAT1 phosphorylation in monocytes, finding that ITA significantly reduced IFN-γ-induced STAT1 phosphorylation. Heliyon. 2024 Jan 20;10(3):e24710
Jurkat cells 25 μM 24 hours Evaluated the effect of ITA on the size of EVs released from Jurkat cells, finding that ITA-J-EVs (455 ±111 nm) were smaller than DMSO and BARI-treated EVs (583 ±137 nm). Heliyon. 2024 Jan 20;10(3):e24710
U937 cells 25 μM 24 hours Evaluated the effect of ITA on the size of EVs released from U937 cells, finding that ITA-U-EVs had a unimodal size distribution (821 ±543 nm), while DMSO and BARI-treated EVs had a bimodal distribution. Heliyon. 2024 Jan 20;10(3):e24710
EGFR-CAR T-cells 100 or 250 nM To study the effect of itacitinib on EGFR-CAR T-cell antigen-specific proliferation. Results showed that itacitinib at 100 or 250 nM did not affect EGFR-CAR T-cell antigen-specific proliferation. Clin Cancer Res. 2020 Dec 1;26(23):6299-6309
GD2-CAR T-cells 100 to 500 nM To study the effect of itacitinib on GD2-CAR T-cell proliferation and cytolytic activity. Results showed that itacitinib at 100–250 nM did not have a significant effect on GD2-CAR T-cell proliferation and could efficiently lyse GD2-expressing tumor cells. Clin Cancer Res. 2020 Dec 1;26(23):6299-6309
Human peripheral blood mononuclear cells (PBMCs) 50 to 1000 nM 10 days To study the effect of itacitinib on T-cell proliferation. Results showed that itacitinib concentrations relevant to the IC50 (50–100 nM) did not have a significant effect on T-cell proliferation. Clin Cancer Res. 2020 Dec 1;26(23):6299-6309

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
BALB/c mice ConA-induced acute inflammation model Oral 60 or 120 mg/kg Single dose To study the effect of itacitinib on CRS-related cytokines. Results showed that itacitinib significantly and dose-dependently reduced the levels of CRS-related cytokines such as IL-6, IL-12, and IFN-γ. Clin Cancer Res. 2020 Dec 1;26(23):6299-6309
NSG mice Xenogeneic graft-versus-host disease (xGVHD) model Oral gavage 3 mg (≈120 mg/kg) Twice daily, from day 3 to day 28 post-transplantation To assess the impact of Itacitinib on xenogeneic graft-versus-host disease (xGVHD). Results showed that Itacitinib-treated mice had significantly longer survival than control mice (median 45 vs 33 days; P<0.001), and exhibited lower absolute numbers of human CD4+ and CD8+ T cells, along with increased frequencies of regulatory T cells (Treg). Bone Marrow Transplant. 2021 Nov;56(11):2672-2681
SD rats COPD model Subcutaneous injection 30mg/kg 14 days Inhibited the JAK-STAT3 signaling pathway, weakening the therapeutic effect of herbs on COPD Evid Based Complement Alternat Med. 2022 May 6;2022:7942623

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.81mL

0.36mL

0.18mL

9.03mL

1.81mL

0.90mL

18.07mL

3.61mL

1.81mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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