Cat. No.: HY-18652

Avutometinib

(Synonyms: Ro 5126766; CH5126766)

6 Cited Publications

Customer Review

Based on 6 publication(s) in Google Scholar

Avutometinib (Ro 5126766) is a first-in-class dual MEK/RAF inhibitor that allosterically inhibits BRAF^V600E, CRAF, MEK, and BRAF (IC₅₀: 8.2, 56, 160 nM, and 190 nM, respectively).

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

Purity: 99.43%
CAS No.: 946128-88-7
Formula: C₂₁H₁₈FN₅O₅S
Molecular Weight:471.46

Storage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

Avutometinib Chemical Structure

CAS No.: 946128-88-7

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Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
- Clinical Trial
Chemical Information
Publications (6)
Solvent & Solubility
- In Vitro
- In Vivo
Protocol
Purity & Documentation
References
Help & FAQs
Classifications
Bioz

Biological Activity

Description

IC₅₀ & Target^[1]

MEK

160 nM (IC₅₀)

BRaf^V600E

8.2 nM (IC₅₀)

Braf

190 nM (IC₅₀)

CRAF

56 nM (IC₅₀)

All MEK Isoforms :

All Raf Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
A549	GI₅₀	3.23 μM Compound: RO-5126766	Cytotoxicity against human A549 cells Cytotoxicity against human A549 cells	[PMID: 34655985]
A549	IC₅₀	1.24 μM Compound: 3; RO5126766	Antiproliferative activity against human A549 cells harboring KRAS G12S mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay Antiproliferative activity against human A549 cells harboring KRAS G12S mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay	[PMID: 32305784]
C32	ED₅₀	0.09 mg/kg Compound: 1, CH5126766/RO5126766	Antitumor activity against human C32 cells xenografted in po dosed BALB-nu/nu mouse assessed as tumor growth inhibition administered qd for 11 days Antitumor activity against human C32 cells xenografted in po dosed BALB-nu/nu mouse assessed as tumor growth inhibition administered qd for 11 days	[PMID: 24900832]
C32	IC₅₀	47 nM Compound: 1, CH5126766/RO5126766	Growth inhibition of human C32 cells harboring R-Raf V600E mutant Growth inhibition of human C32 cells harboring R-Raf V600E mutant	[PMID: 24900832]
HCT-116	GI₅₀	3.23 μM Compound: RO-5126766	Cytotoxicity against human HCT-116 cells Cytotoxicity against human HCT-116 cells	[PMID: 34655985]
HCT-116	IC₅₀	0.053 μM Compound: 3; RO5126766	Antiproliferative activity against human HCT116 cells harboring KRAS G13D mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay Antiproliferative activity against human HCT116 cells harboring KRAS G13D mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay	[PMID: 32305784]
HCT-116	IC₅₀	0.739 μM Compound: Avutometinib	Antiproliferative activity against human HCT-116 cells harboring KRAS G13D mutant incubated for 72 hrs by CCK8 assay Antiproliferative activity against human HCT-116 cells harboring KRAS G13D mutant incubated for 72 hrs by CCK8 assay	[PMID: 39166848]
HCT-116	IC₅₀	277 nM Compound: 1; VS6766	Antiproliferative activity against human HCT-116 cells harboring NRAS G13D mutant assessed as cell growth inhibition measured after 72 hrs by WST-8 assay Antiproliferative activity against human HCT-116 cells harboring NRAS G13D mutant assessed as cell growth inhibition measured after 72 hrs by WST-8 assay	[PMID: 35849914]
HCT-116	IC₅₀	40 nM Compound: 1, CH5126766/RO5126766	Inhibition of human HCT116 cell growth after 96 hrs by counting kit-8 analysis Inhibition of human HCT116 cell growth after 96 hrs by counting kit-8 analysis	[PMID: 24900832]
HL-60	IC₅₀	0.006 μM Compound: 3; RO5126766	Antiproliferative activity against human HL60 cells harboring NRAS K61L mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay Antiproliferative activity against human HL60 cells harboring NRAS K61L mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay	[PMID: 32305784]
L02	IC₅₀	17.27 μM Compound: 3; RO5126766	Cytotoxicity against human HL7702 cells assessed as reduction in cell viability after 96 hrs by Celltiter-Glo assay Cytotoxicity against human HL7702 cells assessed as reduction in cell viability after 96 hrs by Celltiter-Glo assay	[PMID: 32305784]
MDA-MB-231	IC₅₀	0.17 μM Compound: 3; RO5126766	Antiproliferative activity against human MDA-MB-231 cells harboring KRAS G13D/BRAF G464V mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay Antiproliferative activity against human MDA-MB-231 cells harboring KRAS G13D/BRAF G464V mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay	[PMID: 32305784]
MIA PaCa-2	IC₅₀	0.115 μM Compound: Avutometinib	Antiproliferative activity against human MIA PaCa-2 cells harboring KRAS G12C mutant incubated for 72 hrs by CCK8 assay Antiproliferative activity against human MIA PaCa-2 cells harboring KRAS G12C mutant incubated for 72 hrs by CCK8 assay	[PMID: 39166848]
MIA PaCa-2	IC₅₀	40 nM Compound: 1; VS6766	Antiproliferative activity against human MIA PaCa-2 cells harboring NRAS G12C mutant assessed as cell growth inhibition measured after 72 hrs by WST-8 assay Antiproliferative activity against human MIA PaCa-2 cells harboring NRAS G12C mutant assessed as cell growth inhibition measured after 72 hrs by WST-8 assay	[PMID: 35849914]
SK-MEL-2	IC₅₀	28 nM Compound: 1; VS6766	Antiproliferative activity against human SK-MEL-2 cells harboring NRAS Q61R mutant assessed as cell growth inhibition measured after 72 hrs by WST-8 assay Antiproliferative activity against human SK-MEL-2 cells harboring NRAS Q61R mutant assessed as cell growth inhibition measured after 72 hrs by WST-8 assay	[PMID: 35849914]
SK-MEL-28	IC₅₀	65 nM Compound: 1; VS6766	Antiproliferative activity against human SK-MEL-28 cells harboring BRAF V600E mutant assessed as cell growth inhibition measured after 72 hrs by WST-8 assay Antiproliferative activity against human SK-MEL-28 cells harboring BRAF V600E mutant assessed as cell growth inhibition measured after 72 hrs by WST-8 assay	[PMID: 35849914]
SW480	IC₅₀	46 nM Compound: 1; VS6766	Antiproliferative activity against human SW480 cells harboring NRAS G12V mutant assessed as cell growth inhibition measured after 72 hrs by WST-8 assay Antiproliferative activity against human SW480 cells harboring NRAS G12V mutant assessed as cell growth inhibition measured after 72 hrs by WST-8 assay	[PMID: 35849914]
Vero	IC₅₀	>50 μM Compound: 3; RO5126766	Cytotoxicity against African green monkey Vero cells assessed as reduction in cell viability after 96 hrs by Celltiter-Glo assay Cytotoxicity against African green monkey Vero cells assessed as reduction in cell viability after 96 hrs by Celltiter-Glo assay	[PMID: 32305784]

In Vitro

Avutometinib (Ro 5126766) is an allosteric inhibitor that binds directly to MEK and prevents its phosphorylation by RAF through the formation of a stable RAF-MEK complex. Ro 5126766 inhibits both the phosphorylation of MEK by RAF and the activation of ERK by MEK. In cell-free MEK and RAF kinase assays, Avutometinib effectively inhibits activation of ERK2 by MEK1 with an IC₅₀ of 160 nM (SD=±0.043) and inhibits the phosphorylation of MEK1 protein by BRAF (IC₅₀=190 nM, SD=±0.003), BRAF^V600E (IC₅₀=8.2 nM, SD=±0.0015), and CRAF (IC₅₀=56 nM, SD=±0.016). Avutometinib effectively inhibits both MEK and ERK phosphorylation in a panel of human tumor cell lines including KRAS/HRAS and BRAF mutant cell lines and KRAS/HRAS and BRAF wild-type cells^[1]. In order to investigate whether the mevalonate pathway affects the sensitivity to MEK inhibitors, human breast cancer MDA-MB-231 cells harboring KRAS and BRAF mutations are treated Avutometinib, with or without statins, which inhibits HMG-CoA reductase, the rate-limiting enzyme in the mevalonate pathway. The combined treatment of Avutometinib with XU 62-320 demonstrates more significant reduction in cell growth in a dose-dependent manner than the single treatment of Avutometinib. The marked combined effects of Avutometinib at 40 nM and XU 62-320 at 0.3 μM is also confirmed on the suppression of the colony formation of the cells^[2].

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

In Vivo

In KRAS-mutant xenograft models, Avutometinib (Ro 5126766) inhibits growth and causes tumor regressions more effectively than another allosteric MEK inhibitor, PD0325901. Preclinical data from a series of human tumor mouse xenograft models indicates an ED₅₀ for Ro 5126766 of 0.03 to 0.23 mg/kg and an ED₉₀ of 0.15 to 1.56 mg/kg. These effective doses are associated with target trough concentrations of 17 to 133 ng/L and 87 to 901 ng/mL, respectively. ^[1]. In this experiment, Avutometinib or PD0325901 is administrated at their maximum tolerated dose (MTD) in the HCT116 model (1.5 and 25 mg/kg, respectively). These doses inhibit pERK and ERK signaling output at similar degrees in the tumors from the drug-treated mice at 4 hours from the first drug administration. Moreover, in HCT116 models, the ED₅₀ for Avutometinib and PD0325901 are 0.056 and 0.80 mg/kg, respectively. Therefore, the doses used for this experiment are 26.8- and 31.3-fold higher doses than the 50% effective doses, respectively. Daily oral administration of either drug causes significant tumor regression of each these tumors. However, whereas inhibition of tumor growth is maintained for the entire 28-day treatment period in Avutometinib-treated mice, tumor models receiving PD0325901 become refractory after 10 days of treatment^[3].

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

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS No. 946128-88-7
Appearance Solid
Molecular Weight 471.46
Formula C₂₁H₁₈FN₅O₅S
Color White to yellow
SMILES

O=S(NC)(NC1=NC=CC(CC2=C(C)C3=CC=C(OC4=NC=CC=N4)C=C3OC2=O)=C1F)=O
Synonyms

Ro 5126766; CH5126766
Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Publications (6)

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Nat Cancer

The MEK-RAF molecular glue IK-595 has potent antitumor activity across RAS/MAPK pathway-altered cancers. [Abstract]

2026 Jan;7(1):116-130. PMID: 41482524

Avutometinib purchased from MedChemExpress. Usage Cited in: Nat Cancer. 2026 Jan;7(1):116-130. [Abstract]

Western blot analysis of MEK immunoprecipitants depicting the modulation of MEK–BRAF and MEK–CRAF interactions in HCT-116 cells treated with DMSO, trametinib (10 nM), Avutometinib (30 nM), trametiglue (3 nM) or IK-595 (3 nM) for 4 h. A representative image of three independent experiments is shown.

Avutometinib purchased from MedChemExpress. Usage Cited in: Nat Cancer. 2026 Jan;7(1):116-130. [Abstract]

DMSO–inhibitor K_D ratios obtained from an AlphaLISA biochemical assay measuring the interaction between MEK1 and BRAF (top) or CRAF (bottom) proteins following treatment with IK-595 (n = 1 sample per condition with nine biological replicates), trametinib (n = 1 sample per condition with five biological replicates) or Avutometinib (0.01-1 μM; 30 min) (n = 1 sample oer condition with four biological replicates). The results demonstrated that IK-595 and Avutometinib stabilized MEK1 with both BRAF and CRAF, whereas trametinib disrupted these interactions.

Avutometinib purchased from MedChemExpress. Usage Cited in: Nat Cancer. 2026 Jan;7(1):116-130. [Abstract]

Western blot quantification of MEK phosphorylation normalized to total MEK protein levels in HCT-116 cells treated with DMSO, Avutometinib (30 nM), trametinib (10 nM), trametiglue (3 nM), mirdametinib (25 nM), binimetinib (50 nM), selumetinib (550 nM), cobimetinib (320 nM) or IK-595 (3 nM) for 4 or 48 h (n = 1 sample per condition in two biological replicates).
Nat Chem Biol

MEK interactions tune RAF kinase sensitivity to conformation-selective inhibition. [Abstract]

2026 May 12:10.1038/s41589-026-02212-2. PMID: 42120500
Clin Sci (Lond)

A pan-RAF inhibitor LY3009120 inhibits necroptosis by preventing phosphorylation of RIPK1 and alleviates dextran sulfate sodium-induced colitis. [Abstract]

2019 Apr 16;133(8):919-932. PMID: 30944150
Sci Data

High-throughput drug screening identifies novel therapeutics for Low Grade Serous Ovarian Carcinoma. [Abstract]

2024 Sep 19;11(1):1024. PMID: 39300112

Avutometinib purchased from MedChemExpress. Usage Cited in: Sci Data. 2024 Sep 19;11(1):1024. [Abstract]

CEP-32496, Avutometinib (Ro 5126766) (0.1-10 μM; 1 h) and PLX8394 didn’t inhibit necroptosis in L929 cells. L929 or HT-29 cells were pretreated with DMSO or Nec-1 or indicated inhibitors for 1h, then stimulated with T/Z for 3 hours or T/S/Z for 8 hours, respectively. Then cell viability was determined by CCK8 assay.
bioRxiv

2026 Jun 25.
bioRxiv

2024 September 19.

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL (212.11 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

2.1211 mL

10.6054 mL

21.2107 mL

5 mM

0.4242 mL

2.1211 mL

4.2421 mL

10 mM

0.2121 mL

1.0605 mL

2.1211 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, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Molarity Calculator

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

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Molecular Weight Molecular Weight

Dilution Calculator

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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 (5.30 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 (5.30 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 (5.30 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:

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g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
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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^[2]

The number of viable cells is assessed with a Cell Counting Kit-8 assay. Human breast cancer MDA-MB-231 cells, human melanoma SK-MEL-28 cells, and human non-small cell lung cancer A549 cells are seeded at a density of 2,000 cells per well in 96-well plates and incubated for 24 h, and then treated with Ro 5126766 (10, 20, 40, and 80 nM) for 72 h. After a further 4 h incubation with the kit reagent, the absorbance at 450 nm of the samples is measured using a multi-plate reader^[2].

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

Animal Administration^[3]

Mice^[3]
Female BALB-nu/nu mice (CAnN.Cg-Foxn1nu/CrlCrlj nu/nu) are given access to standard mouse chow and water ad libitum. A total of 5×10⁶ (HCT116) or 1×10⁷ (Calu-6 and COLO205) tumor cells per mouse are injected subcutaneously into the right flank of the 7- to 9-week-old mice. When tumor volume reaches to 200 mm³ (day 0), the mice are randomized and vehicle [5% DMSO and 10% 2-hydroxypropyl-β-cyclodextrin (HPCD) solution in distilled water], Avutometinib (1.5 mg/kg or 2.0 mg/kg) or PD0325901 (25 mg/kg) is administered orally once a day. Drugs are administrated at the maximum tolerated dose (MTD). Tumor growth inhibition (TGI) is calculated. The value of the 50% effective dose (ED₅₀) for each compound is calculated^[3].

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 (291 KB)
SDS (396 KB)
- English - EN (396 KB)
- Français - FR (396 KB)
- Deutsch - DE (396 KB)
- Norwegian - NO (396 KB)
- Español - ES (396 KB)
- Swedish - SV (396 KB)
- Italian - IT (396 KB)
- Korean - KR (396 KB)
- Portuguese - PT (396 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]. Martinez-Garcia M, et al. First-in-human, phase I dose-escalation study of the safety, pharmacokinetics, and pharmacodynamics of RO5126766, a first-in-class dual MEK/RAF inhibitor in patients with solid tumors. Clin Cancer Res. 2012 Sep 1;18(17):4806-19. [Content Brief]

[2]. Iizuka-Ohashi M, et al. Blockage of the mevalonate pathway overcomes the apoptotic resistance to MEK inhibitors with suppressing the activation of Akt in cancer cells. Oncotarget. 2018 Apr 13;9(28):19597-19612. [Content Brief]

[3]. Ishii N, et al. Enhanced inhibition of ERK signaling by a novel allosteric MEK inhibitor, CH5126766, that suppresses feedback reactivation of RAF activity. Cancer Res. 2013 Jul 1;73(13):4050-4060. [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, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.1211 mL	10.6054 mL	21.2107 mL	53.0268 mL
	5 mM	0.4242 mL	2.1211 mL	4.2421 mL	10.6054 mL
	10 mM	0.2121 mL	1.0605 mL	2.1211 mL	5.3027 mL
	15 mM	0.1414 mL	0.7070 mL	1.4140 mL	3.5351 mL
	20 mM	0.1061 mL	0.5303 mL	1.0605 mL	2.6513 mL
	25 mM	0.0848 mL	0.4242 mL	0.8484 mL	2.1211 mL
	30 mM	0.0707 mL	0.3535 mL	0.7070 mL	1.7676 mL
	40 mM	0.0530 mL	0.2651 mL	0.5303 mL	1.3257 mL
	50 mM	0.0424 mL	0.2121 mL	0.4242 mL	1.0605 mL
	60 mM	0.0354 mL	0.1768 mL	0.3535 mL	0.8838 mL
	80 mM	0.0265 mL	0.1326 mL	0.2651 mL	0.6628 mL
	100 mM	0.0212 mL	0.1061 mL	0.2121 mL	0.5303 mL

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Avutometinib

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Publications Citing Use of MedChemExpress (MCE) Avutometinib

All MEK Isoforms

All Raf Isoforms

Biological Activity

Chemical Information

Publications (6)

Solvent & Solubility

Protocol

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

Avutometinib Related Classifications

HY-18652 Related Classifications