LY3009120 (Synonyms: DP-4978)

Name: LY3009120
Brand: MedChemExpress
SKU: HY-12558
Rating: 5.0 (17 reviews)

Cat. No.: HY-12558 Purity: 98.66%: FAQs
Data Sheet SDS COA Handling Instructions Technical Support

LY3009120 (DP-4978) is a pan RAF inhibitor which inhibits BRAF^V600E, BRAF^WT and CRAF^WT with IC₅₀s of 5.8, 9.1 and 15 nM, respectively.

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

LY3009120 Chemical Structure

CAS No. : 1454682-72-4

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10 mM * 1 mL in DMSO ready for reconstitution	In-stock	Estimated Time of Arrival: December 31
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10 mM * 1 mL in DMSO	In-stock	Estimated Time of Arrival: December 31
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Customer Review

Based on 17 publication(s) in Google Scholar

14 Publications Citing Use of MCE LY3009120

: LY3009120 purchased from MedChemExpress. Usage Cited in: Clin Sci (Lond). 2019 Apr 16;133(8):919-932. [Abstract]; Colonic proteins on day 7 are tested by immunoblotting to detect p-MLKL, MLKL and cleaved caspase-3 with corresponding antibodies. GAPDH is used as an internal control. Three individual mice from each group are shown.

: LY3009120 purchased from MedChemExpress. Usage Cited in: Clin Sci (Lond). 2019 Apr 16;133(8):919-932. [Abstract]; LY3009120 decreases phosphorylation of RIPK1, RIPK3 and MLKL in T/S/Z treated HT-29 cells. HT-29 cells are pretreated with DMSO or LY3009120 for 1 hour, then treated with T/S/Z for 0, 2, 4 and 6 hours, respectively.

: LY3009120 purchased from MedChemExpress. Usage Cited in: Oncogene. 2018 Oct;37(43):5719-5734. [Abstract]; BRAF mutants with in-frame β3-αC loop deletions have approximate sensitivities to RAF dimer inhibitor, LY3009120.

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BRaf c-Raf Raf

Biological Activity
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References
Customer Review

Description

LY3009120 (DP-4978) is a pan RAF inhibitor which inhibits BRAF^V600E, BRAF^WT and CRAF^WT with IC₅₀s of 5.8, 9.1 and 15 nM, respectively.

IC₅₀ & Target^[1]

BRaf^V600E

5.8 nM (IC₅₀)

Braf

9.1 nM (IC₅₀)

CRAF

15 nM (IC₅₀)

Cellular Effect

Cell Line	Type	Value	Description	References
A-375	IC₅₀	0.0092 μM Compound: 13, LY3009120	Antiproliferative activity against human A375 cells after 72 hrs by resazurin assay Antiproliferative activity against human A375 cells after 72 hrs by resazurin assay	[PMID: 25965804]
A-375	IC₅₀	0.037 μM Compound: 13, LY3009120	Inhibition of BRAF V600E mutant in human A375 cells assessed as inhibition of ERK phosphorylation measured after 72 hrs by ELISA assay Inhibition of BRAF V600E mutant in human A375 cells assessed as inhibition of ERK phosphorylation measured after 72 hrs by ELISA assay	[PMID: 25965804]
A-375	IC₅₀	0.3 μM Compound: LY3009120	Antiproliferative activity against human A375 cells after 72 hrs by Cell-Titer Glo assay Antiproliferative activity against human A375 cells after 72 hrs by Cell-Titer Glo assay	[PMID: 30529543]
A-375	IC₅₀	100 nM Compound: 13, LY3009120	Competitive binding affinity to EphB4 in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to EphB4 in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	20 nM Compound: 13, LY3009120	Competitive binding affinity to EphA2 in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to EphA2 in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	28.3 nM Compound: 1; LY3009120	Antiproliferative activity against human A-375 cells harboring BRAF mutant assessed as reduction in cell viability incubated for 24 hrs by Click-iT EdU cell proliferation imaging assay Antiproliferative activity against human A-375 cells harboring BRAF mutant assessed as reduction in cell viability incubated for 24 hrs by Click-iT EdU cell proliferation imaging assay	[PMID: 33780623]
A-375	IC₅₀	290 nM Compound: 13, LY3009120	Competitive binding affinity to CSK in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to CSK in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	31 nM Compound: 13, LY3009120	Competitive binding affinity to BRAF in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to BRAF in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	310 nM Compound: 13, LY3009120	Competitive binding affinity to SRC in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to SRC in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	380 nM Compound: 13, LY3009120	Competitive binding affinity to ABL in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to ABL in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	39 nM Compound: 13, LY3009120	Competitive binding affinity to ZAK in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to ZAK in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	390 nM Compound: 13, LY3009120	Competitive binding affinity to IRAK1 in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to IRAK1 in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	EC₅₀	4.36 mg/kg Compound: 13, LY3009120	In vivo inhibition of BRAF V600E mutant in human A375 cells xenografted in po dosed NIH nude rat assessed as inhibition of ERK phosphorylation by ELISA In vivo inhibition of BRAF V600E mutant in human A375 cells xenografted in po dosed NIH nude rat assessed as inhibition of ERK phosphorylation by ELISA	[PMID: 25965804]
A-375	IC₅₀	42 nM Compound: 13, LY3009120	Competitive binding affinity to CRAF in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to CRAF in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	44 nM Compound: 13, LY3009120	Competitive binding affinity to ARAF in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to ARAF in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	450 nM Compound: 13, LY3009120	Competitive binding affinity to GCN2 in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to GCN2 in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	470 nM Compound: 13, LY3009120	Competitive binding affinity to JNK in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to JNK in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	61 nM Compound: 13, LY3009120	Competitive binding affinity to p38 in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to p38 in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	800 nM Compound: 13, LY3009120	Competitive binding affinity to MAP2K5 in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to MAP2K5 in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	91 nM Compound: 13, LY3009120	Competitive binding affinity to FYN in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to FYN in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	970 nM Compound: 13, LY3009120	Competitive binding affinity to KHS1 in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to KHS1 in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	98 nM Compound: 13, LY3009120	Competitive binding affinity to MAP3K1 in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to MAP3K1 in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A549	IC₅₀	45.6 nM Compound: 1; LY3009120	Synergistic antiproliferative activity against human A549 cells harboring KRAS mutant assessed as reduction in cell viability incubated for 24 hrs in presence of 100 nM cobimetinib by Click-iT EdU cell proliferation imaging assay Synergistic antiproliferative activity against human A549 cells harboring KRAS mutant assessed as reduction in cell viability incubated for 24 hrs in presence of 100 nM cobimetinib by Click-iT EdU cell proliferation imaging assay	[PMID: 33780623]
A549	IC₅₀	545 nM Compound: 1; LY3009120	Antiproliferative activity against human A549 cells harboring KRAS mutant assessed as reduction in cell viability incubated for 24 hrs by Click-iT EdU cell proliferation imaging assay Antiproliferative activity against human A549 cells harboring KRAS mutant assessed as reduction in cell viability incubated for 24 hrs by Click-iT EdU cell proliferation imaging assay	[PMID: 33780623]
HCT-116	IC₅₀	0.15 μM Compound: 13, LY3009120	Inhibition of KRAS G13D mutant in human HCT116 cells assessed as inhibition of ERK phosphorylation by ELISA Inhibition of KRAS G13D mutant in human HCT116 cells assessed as inhibition of ERK phosphorylation by ELISA	[PMID: 25965804]
HCT-116	IC₅₀	0.22 μM Compound: 13, LY3009120	Antiproliferative activity against human HCT116 cells after 67 hrs by resazurin assay Antiproliferative activity against human HCT116 cells after 67 hrs by resazurin assay	[PMID: 25965804]
HepG2	IC₅₀	2.6 μM Compound: LY3009120	Antiproliferative activity against human HepG2 cells after 72 hrs by Cell-Titer Glo assay Antiproliferative activity against human HepG2 cells after 72 hrs by Cell-Titer Glo assay	[PMID: 30529543]
HT-29	IC₅₀	0.9 μM Compound: LY3009120	Antiproliferative activity against human HT-29 cells after 72 hrs by Cell-Titer Glo assay Antiproliferative activity against human HT-29 cells after 72 hrs by Cell-Titer Glo assay	[PMID: 30529543]
MV4-11	IC₅₀	0.1 μM Compound: LY3009120	Antiproliferative activity against human MV4-11 cells after 72 hrs by Cell-Titer Glo assay Antiproliferative activity against human MV4-11 cells after 72 hrs by Cell-Titer Glo assay	[PMID: 30529543]
SK-MEL-2	IC₅₀	0.2 μM Compound: LY3009120	Antiproliferative activity against human SK-MEL-2 cells after 72 hrs by Cell-Titer Glo assay Antiproliferative activity against human SK-MEL-2 cells after 72 hrs by Cell-Titer Glo assay	[PMID: 30529543]

In Vitro

In the whole-cell based KiNativ assay, LY3009120 shows affinity to each RAF isoform with the IC₅₀ of 44, 31-47 and 42 nM for ARAF, BRAF and CRAF respectively. LY3009120 exhibits anti-proliferative effects on cell lines harboring BRAF^V600E, KRAS^G13 and KRAS^G12 mutations. LY3009120 (1 μM) inhibits the phosphorylation of both MEK1/2 and ERK1/2 in cell lines with high basal levels of pMEK1/2 and pERK1/2 (RKO and HCT 116)^[1]. LY3009120 shows inhibitory effect on tumor cells such as BxPC-3, NCI-H2405 and OV-90 cell lines. LY3009120 (0.01 μM) demonstrates potent and dose-dependent inhibition of phospho-MEK and ERK in all three cell lines. LY3009120 demonstrates a concentration-dependent cell growth inhibition with IC₅₀ values of 0.04, 0.087, and 0.007 μM against H2405, BxPC-3, and OV-90 cells, respectively^[2]. LY3009120 inhibits BRAF^WT, CRAF^WT, BRAF^V600E, and BRAF^V600E+G468A with the IC₅₀ values of 9.1, 15, 5.8, and 17 nM, respectively. LY3009120 induces BRAF-CRAF dimerization but inhibits the phosphorylation of downstream MEK and ERK. LY3009120 also inhibits various forms of RAF dimers including BRAF or CRAF homodimers^[3]. LY3009120 gives only very minor activation at very low doses, with near complete inhibition of phospho-ERK at concentrations above 100 nM^[4].

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

In Vivo

LY3009120 (20 mg/kg bid) displays significant activity in in vivo BRAF^mut and KRAS^mut CRC xenograft models. In Colo 205 xenografts (BRAF^mut), LY3009120 results in statistically significant tumor regression, while treatment of HCT 116 xenografts (KRAS^mut) results in statistically significant inhibition of tumor growth. LY3009120 treatment reduces pMEK1/2 in all HT-29 xenografts and reduces pERK1/2 in the majority of HT-29 xenografts^[1]. LY3009120 (15 or 30 mg/kg) achieves almost complete tumor growth regression, and inhibits downstream phospho-MEK and ERK by approximately 70% and 60%, respectively, in the H2405 model^[2].

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

Clinical Trial

Molecular Weight

424.51

Formula

C₂₃H₂₉FN₆O

CAS No.

1454682-72-4

Appearance

Solid

Color

Light yellow to khaki

SMILES

O=C(NC1=CC(C2=CC3=CN=C(NC)N=C3N=C2C)=C(C)C=C1F)NCCC(C)(C)C

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 : ≥ 38 mg/mL (89.51 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.3557 mL	11.7783 mL	23.5566 mL
5 mM	0.4711 mL	2.3557 mL	4.7113 mL
10 mM	0.2356 mL	1.1778 mL	2.3557 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

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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: 5% DMSO 95% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (5.89 mM); Suspended solution; Need ultrasonic

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

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

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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).

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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: 98.66%

Select Batch:

Data Sheet (278 KB) SDS (393 KB)

COA (245 KB)

Handling Instructions (2659 KB)

References

[1]. Vakana E, et al. LY3009120, a panRAF inhibitor, has significant anti-tumor activity in BRAF and KRAS mutant preclinical models of colorectal cancer. Oncotarget. 2017 Feb 7;8(6):9251-9266 [Content Brief]

[2]. Chen SH, et al. Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120. Cancer Discov. 2016 Mar;6(3):300-15 [Content Brief]

[3]. Peng SB, et al. Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers. Cancer Cell. 2015 Sep 14;28(3):384-98 [Content Brief]

[4]. Henry JR, et al. Discovery of 1-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)urea (LY3009120) as a pan-RAF inhibitor with minimal paradoxical activation and activity against BRAF or RAS mutant tumo [Content Brief]

Cell Assay ^[4]	Briefly, cells are grown in McCoy’s 5A supplemented with 10% characterized fetal bovine serum at 37°C, 5% CO₂, and 95% humidity. Cells are allowed to expand until 75-90% confluency at which point they are subcultured or harvested for assay use. A serial dilution of test compound is dispensed into a 384-well black clear bottom plate in triplicate. Six-hundred-twenty-five cells are added per well in 50 μL of complete growth medium in the 384-well plate. Plates are incubated for 67 h at 37°C, 5% CO₂, and 95% humidity. At the end of the incubation period, 10 μL of a 440 μM solution of resazurin in PBS is added to each well of the plate and plates are incubated for an additional 5 h at 37°C, 5% CO₂, and 95% humidity. Plates are read on a Synergy2 reader using an excitation of 540 nm and an emission of 600 nm. Data are analyzed using Prism softwareto calculate IC₅₀ values. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[2]	Briefly, 5×10⁶ to 10×10⁶ tumor cells in a 1:1 Matrigel mix (0.2 mL total volume) are injected subcutaneously into the right hind flank of female NIH nude rats. After tumors reach a desired size of approximately 300 mm³, animals are randomized into groups of 8 for efficacy studies. Drugs (LY3009120 or PLX4032) are administered orally (gavage) in 0.6-mL volume of vehicle with the dose schedules. Tumor growth and body weight are monitored over time to evaluate efficacy and signs of toxicity. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[1]. Vakana E, et al. LY3009120, a panRAF inhibitor, has significant anti-tumor activity in BRAF and KRAS mutant preclinical models of colorectal cancer. Oncotarget. 2017 Feb 7;8(6):9251-9266 [Content Brief] [2]. Chen SH, et al. Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120. Cancer Discov. 2016 Mar;6(3):300-15 [Content Brief] [3]. Peng SB, et al. Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers. Cancer Cell. 2015 Sep 14;28(3):384-98 [Content Brief] [4]. Henry JR, et al. Discovery of 1-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)urea (LY3009120) as a pan-RAF inhibitor with minimal paradoxical activation and activity against BRAF or RAS mutant tumo [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	2.3557 mL	11.7783 mL	23.5566 mL	58.8914 mL
	5 mM	0.4711 mL	2.3557 mL	4.7113 mL	11.7783 mL
	10 mM	0.2356 mL	1.1778 mL	2.3557 mL	5.8891 mL
	15 mM	0.1570 mL	0.7852 mL	1.5704 mL	3.9261 mL
	20 mM	0.1178 mL	0.5889 mL	1.1778 mL	2.9446 mL
	25 mM	0.0942 mL	0.4711 mL	0.9423 mL	2.3557 mL
	30 mM	0.0785 mL	0.3926 mL	0.7852 mL	1.9630 mL
	40 mM	0.0589 mL	0.2945 mL	0.5889 mL	1.4723 mL
	50 mM	0.0471 mL	0.2356 mL	0.4711 mL	1.1778 mL
	60 mM	0.0393 mL	0.1963 mL	0.3926 mL	0.9815 mL
	80 mM	0.0294 mL	0.1472 mL	0.2945 mL	0.7361 mL

LY3009120 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:

LY30091201454682-72-4DP-4978LY 3009120LY-3009120DP4978DP 4978RafAutophagyRaf kinasesInhibitorinhibitorinhibit

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LY3009120 (Synonyms: DP-4978)

Customer Review

LY3009120 Related Antibodies

14 Publications Citing Use of MCE LY3009120

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Biological Activity

Protocol

Purity & Documentation

References

Customer Review

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Complete Stock Solution Preparation Table

LY3009120 Related Classifications

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