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Chemical Structure| 1188910-76-0 Chemical Structure| 1188910-76-0

Structure of Agerafenib
CAS No.: 1188910-76-0

Chemical Structure| 1188910-76-0

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CEP-32496 is an inhibitor of BRAF V600E (IC50 = 14 nM), WT (IC50 = 34 nM) and c-Raf (IC50 = 39 nM). It also exhibits certain inhibitory activity against Abl-1, c-Kit, Ret, PDGFRβ and VEGFR2.

Synonyms: RXDX-105; CEP-32496

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Product Details of Agerafenib

CAS No. :1188910-76-0
Formula : C24H22F3N5O5
M.W : 517.46
SMILES Code : O=C(NC1=NOC(C(C)(C)C(F)(F)F)=C1)NC2=CC=CC(OC3=C4C=C(OC)C(OC)=CC4=NC=N3)=C2
Synonyms :
RXDX-105; CEP-32496
MDL No. :MFCD22124524
InChI Key :DKNUPRMJNUQNHR-UHFFFAOYSA-N
Pubchem ID :56846693

Safety of Agerafenib

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

Related Pathways of Agerafenib

RTK
MAPK

Isoform Comparison

Biological Activity

Target
  • B-Raf

    B-Raf, Kd:36 nM

    B-Raf (V600E), Kd:14 nM

  • C-Raf/Raf-1

    C-Raf, Kd:39 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
HBEC3KT-RET cells 1 μmol/L 30 minutes To evaluate the inhibitory effect of RXDX-105 on phosphorylation of RET, AKT, and ERK. Results showed that RXDX-105 significantly reduced phosphorylation levels of these proteins. PMC5477238
TT cells 50 nmol/L to 5 μmol/L 2 hours To evaluate the inhibitory effect of RXDX-105 on phosphorylation of RET and PLCγ. Results showed that RXDX-105 significantly reduced phosphorylation levels of RET and PLCγ. PMC5477238
LC-2/ad cells 50 nmol/L to 5 μmol/L 2 hours To evaluate the inhibitory effect of RXDX-105 on phosphorylation of RET and PLCγ. Results showed that RXDX-105 significantly reduced phosphorylation levels of RET and PLCγ. PMC5477238

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
BALB/c nude mice HBEC3KT-RET xenograft model Oral 50 mg/kg and 100 mg/kg Once daily for 5 consecutive days followed by a 2-day dosing break per 7-day cycle To evaluate the inhibitory effect of RXDX-105 on tumor growth. Results showed that at the dose of 100 mg/kg, all tumors shrank more than 30% in size, with an average regression of approximately 50%. PMC5477238
BALB/c nude mice Subcutaneous CRC xenograft model Intraperitoneal injection 3 mg/kg Every 2 days Evaluated synergistic effect of VER155008 with Agerafenib, showing significant antitumor effect PMC10797426

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT01877811 Solid Tumors PHASE1 COMPLETED 2025-02-19 City of Hope, Duarte, Californ... More >>ia, United States|University of California Irvine College of Medicine, Irvine, California, United States|University of California San Diego Moores Cancer Center, San Diego, California, United States|Lombardi Comprehensive Cancer Center, Georgetown, Washington, District of Columbia, United States|Florida Cancer Center, Sarasota, Florida, United States|University Cancer & Blood Center, LLC, Athens, Georgia, United States|Massachusetts General Hospital/Beth Israel Deaconess Med. Ctr./Dana Farber Cancer Institute, Boston, Massachusetts, United States|Henry Ford Health System, Detroit, Michigan, United States|Karmanos Cancer Center, Detroit, Michigan, United States|Washington University, Saint Louis, Missouri, United States|Memorial Sloan Kettering Cancer Center, New York, New York, United States|Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States|University of Texas MD Anderson Cancer Center, Houston, Texas, United States|University of Washington, Seattle Cancer Care Alliance, Seattle, Washington, United States Less <<
NCT03052569 Cancers With RET Alterations NO_LONGER_AVAILABLE - Www.Ignyta.Com, San Diego, Cal... More >>ifornia, 92121, United States Less <<
NCT03784378 Non Small Cell Lung Cancer|Ova... More >>rian Cancer|RET Gene Mutation|BRAF Gene Mutation Less << PHASE1 COMPLETED 2020-09-30 Memorial Sloan Kettering Cance... More >>r Center 1275 York Avenue, New York, New York, 10065, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.93mL

0.39mL

0.19mL

9.66mL

1.93mL

0.97mL

19.33mL

3.87mL

1.93mL

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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