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Chemical Structure| 895519-90-1 Chemical Structure| 895519-90-1

Structure of Flumatinib
CAS No.: 895519-90-1

Chemical Structure| 895519-90-1

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Flumatinib is a multi-kinase inhibitor with IC50 Values of 1.2 nM, 307.6 nM and 2662 nM for c-Abl, PDGFRβ and c-Kit respectively.

Synonyms: HHGV678

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Product Details of Flumatinib

CAS No. :895519-90-1
Formula : C29H29F3N8O
M.W : 562.59
SMILES Code : O=C(NC1=CC(NC2=NC=CC(C3=CC=CN=C3)=N2)=C(C)N=C1)C4=CC=C(CN5CCN(C)CC5)C(C(F)(F)F)=C4
Synonyms :
HHGV678
MDL No. :MFCD18633213

Safety of Flumatinib

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Flumatinib

RTK

Isoform Comparison

Biological Activity

Description
Flumatinib (HHGV678) is an oral, selective Bcr-Abl inhibitor. It effectively targets c-Abl, PDGFRβ, and c-Kit with IC50 values of 1.2 nM, 307.6 nM, and 665.5 nM, respectively [1].

In Vitro:

Cell Line
Concentration Treated Time Description References
32D-N822K 16.5 nM 72 hours Evaluate the antiproliferative activity of Flumatinib against N822K-mutant KIT, showing effective inhibition. Cancer Sci. 2014 Jan;105(1):117-25
32D-V559D+Y823D 6.3 nM 72 hours Evaluate the antiproliferative activity of Flumatinib against KIT mutants with activation loop mutations, showing efficacy in overcoming resistance conferred by Y823D. Cancer Sci. 2014 Jan;105(1):117-25
32D-V559D 4.3 nM 72 hours Evaluate the antiproliferative activity of Flumatinib against KIT-mutant cells, showing high efficacy against 32D-V559D cells. Cancer Sci. 2014 Jan;105(1):117-25
recombinant human CYP3A4 (rCYP3A4) 0.05, 0.1, 0.2, 0.5, 1, 2 μM 45 minutes Determine the metabolic kinetic parameters of Flumatinib in rCYP3A4, with Km of 3.06 μM and IC50 of 2.90 μM Front Pharmacol. 2023 May 4;14:1168852
rat liver microsomes (RLM) 0.1, 0.5, 1, 2, 5, 10, 20 μM 45 minutes Determine the metabolic kinetic parameters of Flumatinib in RLM, with Km of 2.20 μM and IC50 of 0.62 μM Front Pharmacol. 2023 May 4;14:1168852
human liver microsomes (HLM) 1, 2, 5, 10, 20, 50 μM 45 minutes Determine the metabolic kinetic parameters of Flumatinib in HLM, with Km of 29.28 μM and IC50 of 6.66 μM Front Pharmacol. 2023 May 4;14:1168852
K562/FLM 50 nM 30 days Evaluation of resistance mechanisms in K562/FLM cells, revealing evasion of flumatinib cytotoxicity through enhanced autophagy, increased membrane transport protein expression, and activation of the EGFR/ERK/STAT3 signaling pathway. J Cell Mol Med. 2024 Jul;28(14):e18539
K562 0.5 nM to 50 nM 7-14 days per concentration increment Establishment of flumatinib-resistant K562/FLM cell line, which exhibited cross-resistance to imatinib and doxorubicin but remained sensitive to ivermectin. J Cell Mol Med. 2024 Jul;28(14):e18539

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Balb/cA-nu/nu mice 32D-V559D+Y823D cell xenograft model Oral gavage 75 mg/kg Once or twice daily for 14 days Evaluate the in vivo antitumor efficacy of Flumatinib, showing significant prolongation of survival in mice bearing 32D-V559D+Y823D cells. Cancer Sci. 2014 Jan;105(1):117-25
SD rats Oral 60 mg/kg Flumatinib and 20 mg/kg Isavuconazole Single dose Study the effect of Isavuconazole on the pharmacokinetics of Flumatinib, results showed AUC(0–t), AUC(0–∞) and Cmax increased by 1.72, 1.88 and 1.70 times, respectively, and CLz/F decreased by 48% Front Pharmacol. 2023 May 4;14:1168852

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT04375683 Acute Lymphocytic Leukemia, Ad... More >>ult B-Cell|BCR-ABL1 Fusion Protein Expression Less << PHASE3 UNKNOWN 2022-12-30 Department of Hematology, Zhon... More >>gda Hospital Southeast University, Institute of Hematology Southeast University, Nanjing, Jiangsu, 210009, China|Department of Hematology, Zhongda Hospital Southeast University, Institute of Hematology Southeast University, Nanjing, Jiangsu, 210009, China Less <<
NCT04677439 Flumatinib|Chronic Myeloid Leu... More >>kemia, Chronic Phase|Imatinib Less << PHASE4 UNKNOWN 2023-12-30 The Second People's Hospital o... More >>f Shenzhen, Shenzhen, Guangdong, 518035, China Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.78mL

0.36mL

0.18mL

8.89mL

1.78mL

0.89mL

17.77mL

3.55mL

1.78mL

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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