Cat. No.: HY-15200

Agerafenib

(Synonyms: CEP-32496; RXDX-105)

8 Cited Publications

Customer Review

Based on 8 publication(s) in Google Scholar

Agerafenib (CEP-32496; RXDX-105) is a highly potent and orally efficacious inhibitor of BRAF^V600E with a K_d of 14 nM.

For research use only. We do not sell to patients.

Purity: 99.78%
CAS No.: 1188910-76-0
Formula: C₂₄H₂₂F₃N₅O₅
Molecular Weight:517.46

Storage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

Agerafenib Chemical Structure

CAS No.: 1188910-76-0

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Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Publications (8)
Solvent & Solubility
- In Vitro
- In Vivo
Protocol
Purity & Documentation
References
Help & FAQs
Bioz

Biological Activity

Description

Agerafenib (CEP-32496; RXDX-105) is a highly potent and orally efficacious inhibitor of BRAF^V600E with a K_d of 14 nM.

IC₅₀ & Target^[1]

BRaf^V600E

14 nM (Kd)

Braf

36 nM (Kd)

CRAF

39 nM (Kd)

c-Kit

2 nM (Kd)

Ret

2 nM (Kd)

LCK

2 nM (Kd)

Abl-1

3 nM (Kd)

VEGFR-2

8 nM (Kd)

CSF-1R

9 nM (Kd)

EPHA2

14 nM (Kd)

EGFR

22 nM (Kd)

c-Met

513 nM (Kd)

JAK-2

4700 nM (Kd)

MEK-1

7100 nM (Kd)

MEK-2

8300 nM (Kd)

All Raf Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
A-375	IC₅₀	78 nM Compound: 40, CEP-32496	Cytotoxicity against human A375 cells expressing BRAF V600E mutant after 72 hrs by cell titer blue assay Cytotoxicity against human A375 cells expressing BRAF V600E mutant after 72 hrs by cell titer blue assay	[PMID: 22168626]
A-375	IC₅₀	82 nM Compound: 40, CEP-32496	Inhibition of BRAF V600E mutant-mediated MEK phosphorylation in human A375 cells after 2 hrs Inhibition of BRAF V600E mutant-mediated MEK phosphorylation in human A375 cells after 2 hrs	[PMID: 22168626]
A-375	GI₅₀	84 nM Compound: Agerafenib	Cytotoxicity against human A-375 cells expressing BRAF V600E mutant incubated for 72 hrs by celltitre blue assay Cytotoxicity against human A-375 cells expressing BRAF V600E mutant incubated for 72 hrs by celltitre blue assay	[PMID: 34402300]
A-431	GI₅₀	1 μM Compound: Agerafenib	Cytotoxicity against human A-431 cells expressing C-KIT incubated for 72 hrs by celltitre blue assay Cytotoxicity against human A-431 cells expressing C-KIT incubated for 72 hrs by celltitre blue assay	[PMID: 34402300]
COLO 205	EC₅₀	36 nM Compound: 40, CEP-32496	Cytotoxicity against human COLO205 cells expressing BRAF V600E mutant after 72 hrs by cell titer blue assay Cytotoxicity against human COLO205 cells expressing BRAF V600E mutant after 72 hrs by cell titer blue assay	[PMID: 22168626]
COLO 205	GI₅₀	60 nM Compound: Agerafenib	Cytotoxicity against human COLO 205 cells expressing BRAF V600E mutant incubated for 72 hrs by celltitre blue assay Cytotoxicity against human COLO 205 cells expressing BRAF V600E mutant incubated for 72 hrs by celltitre blue assay	[PMID: 34402300]
COLO-679	EC₅₀	211 nM Compound: 40, CEP-32496	Cytotoxicity against human COLO679 cells expressing BRAF V600E mutant after 72 hrs by cell titer blue assay Cytotoxicity against human COLO679 cells expressing BRAF V600E mutant after 72 hrs by cell titer blue assay	[PMID: 22168626]
DU-145	EC₅₀	2911 nM Compound: 40, CEP-32496	Cytotoxicity against human DU145 cells expressing wild type BRAF after 72 hrs by cell titer blue assay Cytotoxicity against human DU145 cells expressing wild type BRAF after 72 hrs by cell titer blue assay	[PMID: 22168626]
HCT-116	EC₅₀	669 nM Compound: 40, CEP-32496	Cytotoxicity against human HCT116 cells expressing wild type BRAF after 72 hrs by cell titer blue assay Cytotoxicity against human HCT116 cells expressing wild type BRAF after 72 hrs by cell titer blue assay	[PMID: 22168626]
HeLa	GI₅₀	≥3 μM Compound: Agerafenib	Cytotoxicity against human HeLa cells expressing CRAF incubated for 72 hrs by celltitre blue assay Cytotoxicity against human HeLa cells expressing CRAF incubated for 72 hrs by celltitre blue assay	[PMID: 34402300]
Hs-578T	EC₅₀	2736 nM Compound: 40, CEP-32496	Cytotoxicity against human Hs578T cells expressing wild type BRAF after 72 hrs by cell titer blue assay Cytotoxicity against human Hs578T cells expressing wild type BRAF after 72 hrs by cell titer blue assay	[PMID: 22168626]
Hs-578T	GI₅₀	2736 nM Compound: Agerafenib	Cytotoxicity against human Hs-578T cells expressing BRAF incubated for 72 hrs by celltitre blue assay Cytotoxicity against human Hs-578T cells expressing BRAF incubated for 72 hrs by celltitre blue assay	[PMID: 34402300]
HT-144	EC₅₀	228 nM Compound: 40, CEP-32496	Cytotoxicity against human HT144 cells expressing BRAF V600E mutant after 72 hrs by cell titer blue assay Cytotoxicity against human HT144 cells expressing BRAF V600E mutant after 72 hrs by cell titer blue assay	[PMID: 22168626]
HUVEC	GI₅₀	≥1 μM Compound: Agerafenib	Cytotoxicity against HUVEC expressing FLT-1 incubated for 72 hrs by celltitre blue assay Cytotoxicity against HUVEC expressing FLT-1 incubated for 72 hrs by celltitre blue assay	[PMID: 34402300]
HUVEC	GI₅₀	≥700 nM Compound: Agerafenib	Cytotoxicity against HUVEC expressing VEGFR2 incubated for 72 hrs by celltitre blue assay Cytotoxicity against HUVEC expressing VEGFR2 incubated for 72 hrs by celltitre blue assay	[PMID: 34402300]
K562	GI₅₀	39 nM Compound: Agerafenib	Cytotoxicity against human K562 cells expressing ABL incubated for 72 hrs by celltitre blue assay Cytotoxicity against human K562 cells expressing ABL incubated for 72 hrs by celltitre blue assay	[PMID: 34402300]
K562	GI₅₀	70 nM Compound: Agerafenib	Cytotoxicity against human K562 cells expressing BCR-ABL incubated for 72 hrs by celltitre blue assay Cytotoxicity against human K562 cells expressing BCR-ABL incubated for 72 hrs by celltitre blue assay	[PMID: 34402300]
LNCaP	EC₅₀	6631 nM Compound: 40, CEP-32496	Cytotoxicity against human LNCAP cells expressing wild type BRAF after 72 hrs by cell titer blue assay Cytotoxicity against human LNCAP cells expressing wild type BRAF after 72 hrs by cell titer blue assay	[PMID: 22168626]
LNCaP	GI₅₀	6631 nM Compound: Agerafenib	Cytotoxicity against human LNCaP cells expressing BRAF incubated for 72 hrs by celltitre blue assay Cytotoxicity against human LNCaP cells expressing BRAF incubated for 72 hrs by celltitre blue assay	[PMID: 34402300]
PC-3	EC₅₀	6257 nM Compound: 40, CEP-32496	Cytotoxicity against human PC3 cells expressing wild type BRAF after 72 hrs by cell titer blue assay Cytotoxicity against human PC3 cells expressing wild type BRAF after 72 hrs by cell titer blue assay	[PMID: 22168626]
SK-MEL-28	EC₅₀	454 nM Compound: 40, CEP-32496	Cytotoxicity against human SK-MEL-28 cells expressing BRAF V600E mutant after 72 hrs by cell titer blue assay Cytotoxicity against human SK-MEL-28 cells expressing BRAF V600E mutant after 72 hrs by cell titer blue assay	[PMID: 22168626]

In Vitro

Agerafenib (CEP-32496) exhibits high potency against several BRAF^V600E-dependent cell lines and selective cytotoxicity for tumor cell lines expressing mutant BRAF^V600E versus those containing wild-type BRAF. Agerafenib exhibits potent binding (BRAF^V600E K_d=14 nM) and cellular activity (pMEK IC₅₀=82 nM and A375 proliferation IC₅₀=78 nM), with activity in the proliferation assay. Agerafenib also exhibits a favorable CYP450 inhibition profile, with measured IC₅₀ values greater than 10 μM versus the CYP1A2, CYP2C9, CYP2D6, and CYP3A4 isoforms and an IC₅₀=3.4 μM^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Oral administration of Agerafenib (CEP-32496) to Colo-205 tumor xenograft-bearing mice results in significant inhibition of pMEK in tumor cell lysates. For instance, a single 30 mg/kg (po) dose of Agerafenib leads to a 50 and 75% inhibition of normalized pMEK in tumor lysates at the 2 and 6 h postdose time point, respectively (p<0.03), while a 55 mg/kg (po) dose resulted in a 75% to 57% (p<0.03) inhibition of pMEK at 2 through 10 h post administration, with normalization to baseline by 24 h. Agerafenib exhibits an exceptional PK profile in mouse, dog, and cynomolgus monkey. Administration of Agerafenib to beagle dogs (single dose of 1 mg/kg iv and 10 mg/kg po) results in low clearance (CL=5.0 (mL/min)/kg) and excellent bioavailability (%F=100). Similarly, in cynomolgus monkey, the administration of Agerafenib (single dose of 1 mg/kg iv and 10 mg/kg po) leads to high oral exposure due to low clearance (CL=6.7 mL/min/kg) and excellent bioavailability (%F=100)^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Chemical Information

CAS No. 1188910-76-0
Appearance Solid
Molecular Weight 517.46
Formula C₂₄H₂₂F₃N₅O₅
Color White to off-white
SMILES

O=C(NC1=NOC(C(C)(C)C(F)(F)F)=C1)NC2=CC=CC(OC3=C(C=C(OC)C(OC)=C4)C4=NC=N3)=C2
Synonyms

CEP-32496; RXDX-105
Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Publications (8)

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Journal Impact Factor

Science

The target landscape of clinical kinase drugs. [Abstract]

2017 Dec 1;358(6367):eaan4368. PMID: 29191878
Nat Biomed Eng

TLR7/8-agonist-loaded nanoparticles promote the polarization of tumour-associated macrophages to enhance cancer immunotherapy. [Abstract]

2018 Aug;2(8):578-588. PMID: 31015631
Sci Transl Med

PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells. [Abstract]

2018 Jul 18;10(450):eaaq1093. PMID: 30021885
Adv Sci (Weinh)

HSPA8 Activates Wnt/β-Catenin Signaling to Facilitate BRAF V600E Colorectal Cancer Progression by CMA-Mediated CAV1 Degradation. [Abstract]

2024 Jan;11(3):e2306535. PMID: 37973552
J Med Virol

Small molecule RAF265 as an antiviral therapy acts against HSV-1 by regulating cytoskeleton rearrangement and cellular translation machinery. [Abstract]

2023 Jan;95(1):e28226. PMID: 36251738
Patent

US20220098204A1.
Patent

US20210379056A1.
Technical University of Munich

24.01.2018.

Solvent & Solubility

In Vitro:

DMSO : 50 mg/mL (96.63 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.9325 mL

9.6626 mL

19.3252 mL

5 mM

0.3865 mL

1.9325 mL

3.8650 mL

10 mM

0.1933 mL

0.9663 mL

1.9325 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Dilution Calculator

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

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In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 2.5 mg/mL (4.83 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)

Solubility: ≥ 2.5 mg/mL (4.83 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (4.83 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Protocol

Cell Assay^[1]

A375 cells are seeded at 10,000 cells per well in DMEM with 10% fetal calf serum and allowed to attach. The cells are washed with PBS and switched to DMEM with 0.5% of serum and incubated overnight. The test compounds (e.g., Agerafenib; 10 μM) are then added at various concentrations with a final DMSO concentration of 0.5% and incubated for 72 h. At the end of incubation, a Cell Titer Blue is added per instructions, and incubation is continued for 3 h. Remaining viable cells are quantified by measuring the strength of the fluorescence signal using SoftMax Pro (excitation at 560 nm and emission at 590 nm). IC₅₀ values are derived using a 9-point curve and are presented as mean values from experiments performed in duplicate^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration^[1]

Mice^[1]
Six to eight week old athymic nu/nu nude mice (20-25 g) are inoculated subcutaneously with Colo-205 tumor cells (1×10⁶/mouse) in the right flank. Upon reaching an average tumor volume of 150-200 mm³ (10-12 days post implantation), animals are randomized into treatment groups (n=10 mice/group). Each group is dosed orally for 14 days with either vehicle only (22% HPβCD) or with Agerafenib at 10, 30, or 100 mg/kg twice daily (BID), and each dose of drug is given in a volume of 0.1 mL per 20 g of body weight, adjusted for the body weight of the animal. Tumor volumes are measured three times weekly using vernier calipers, and volumes are calculated^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (280 KB)
SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Portuguese - PT (254 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Rowbottom MW, et al. Identification of 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)urea hydrochloride (CEP-32496), a highly potent and orally efficacious inhibitor of V-RAF murine sarcoma viral oncogene homologue B1 (BRAF) V600E. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	1.9325 mL	9.6626 mL	19.3252 mL	48.3129 mL
	5 mM	0.3865 mL	1.9325 mL	3.8650 mL	9.6626 mL
	10 mM	0.1933 mL	0.9663 mL	1.9325 mL	4.8313 mL
	15 mM	0.1288 mL	0.6442 mL	1.2883 mL	3.2209 mL
	20 mM	0.0966 mL	0.4831 mL	0.9663 mL	2.4156 mL
	25 mM	0.0773 mL	0.3865 mL	0.7730 mL	1.9325 mL
	30 mM	0.0644 mL	0.3221 mL	0.6442 mL	1.6104 mL
	40 mM	0.0483 mL	0.2416 mL	0.4831 mL	1.2078 mL
	50 mM	0.0387 mL	0.1933 mL	0.3865 mL	0.9663 mL
	60 mM	0.0322 mL	0.1610 mL	0.3221 mL	0.8052 mL
	80 mM	0.0242 mL	0.1208 mL	0.2416 mL	0.6039 mL

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Agerafenib

Immunology/Inflammation Compound Library

Kinase Inhibitor Library

MAPK Compound Library

Anti-Cancer Compound Library

Oxygen Sensing Compound Library

Ferroptosis Compound Library

Orally Active Compound Library

Glutamine Metabolism Compound Library

Anti-Pancreatic Cancer Compound Library

Anti-Obesity Compound Library

Anti-Liver Cancer Compound Library

Anti-Colorectal Cancer Compound Library

Membrane Receptor-targeted Compound Library

Serine/Threonine Kinase Inhibitor Library

Multi-Target Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

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Anti-Brain Cancer Compound Library

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Posttranslational Modification Library

Publications Citing Use of MedChemExpress (MCE) Agerafenib

All Raf Isoforms

Biological Activity

Chemical Information

Publications (8)

Solvent & Solubility

Protocol

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

Agerafenib

Immunology/Inflammation Compound Library

Kinase Inhibitor Library

MAPK Compound Library

Anti-Cancer Compound Library

Oxygen Sensing Compound Library

Ferroptosis Compound Library

Orally Active Compound Library

Glutamine Metabolism Compound Library

Anti-Pancreatic Cancer Compound Library

Anti-Obesity Compound Library

Anti-Liver Cancer Compound Library

Anti-Colorectal Cancer Compound Library

Membrane Receptor-targeted Compound Library

Serine/Threonine Kinase Inhibitor Library

Multi-Target Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

Anti-Brain Cancer Compound Library

Protein Kinase Compound Library

Cell Proliferation Compound Library

High-Throughput Bioactive Compound Library

Posttranslational Modification Library

Publications Citing Use of MedChemExpress (MCE) Agerafenib

All Raf Isoforms

Biological Activity

Chemical Information

Publications (8)

Solvent & Solubility

Protocol

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

Agerafenib Related Classifications

Cat. No.: HY-15200