Agerafenib (Synonyms: CEP-32496; RXDX-105)

Name: Agerafenib
Brand: MedChemExpress
SKU: HY-15200
Rating: 5.0 (8 reviews)

Cat. No.: HY-15200 Purity: 99.63%: FAQs
Data Sheet SDS COA Handling Instructions

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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.

Agerafenib Chemical Structure

CAS No. : 1188910-76-0

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Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 125	In-stock	Estimated Time of Arrival: December 31
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10 mM * 1 mL in DMSO	USD 125	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 110	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 165	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 495	In-stock	Estimated Time of Arrival: December 31
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Customer Review

Based on 8 publication(s) in Google Scholar

Other Forms of Agerafenib:

Agerafenib hydrochloride Get quote

8 Publications Citing Use of MCE Agerafenib

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BRaf c-Raf Raf

Biological Activity
Protocol
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References
Customer Review

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)

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	1000 nM 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	≥ 3000 nM 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	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]
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]
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	≥ 1000 nM 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	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]
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]
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.

Clinical Trial

Molecular Weight

517.46

Formula

C₂₄H₂₂F₃N₅O₅

CAS No.

1188910-76-0

Appearance

Solid

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

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

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)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

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

View the Complete Stock Solution Preparation Table

* 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
Dilution Calculator

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

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

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

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

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.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
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.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
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

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

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

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

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).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 99.63%

Select Batch:

Data Sheet (280 KB) SDS (252 KB)

COA (250 KB) LCMS (266 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]

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

Complete Stock Solution Preparation Table

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

Agerafenib Related Classifications

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

Agerafenib1188910-76-0CEP-32496 RXDX-105CEP32496CEP 32496RXDX105RXDX 105RXDX-105RafRaf kinasesInhibitorinhibitorinhibit

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Agerafenib (Synonyms: CEP-32496; RXDX-105)

Customer Review

Other Forms of Agerafenib:

Agerafenib Related Antibodies

8 Publications Citing Use of MCE Agerafenib

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•Related Screening Libraries:

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View All Raf Isoform Specific Products:

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Protocol

Purity & Documentation

References

Customer Review

Agerafenib Related Antibodies

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Complete Stock Solution Preparation Table

Agerafenib Related Classifications

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