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GMB-475 PROTAC chemical

Name: GMB-475
Brand: Selleck Chemicals
SKU: S8888
Availability: InStock
Rating: 5 (1 reviews)

Cat.No.S8888

GMB-475 is a proteolysis-targeting chimera (PROTAC) that allosterically targets BCR-ABL1 protein and recruit the E3 ligase Von Hippel-Lindau (VHL), resulting in ubiquitination and subsequent degradation of the oncogenic fusion protein.

Chemical Structure

Molecular Weight: 861.93

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability

Quality Control

Batch: Purity: 99.58%

99.58

Related Targets	EGFR VEGFR JAK PDGFR FGFR Src FLT3 HER2 Bcr-Abl HIF BTK ALK Syk FAK VDA
Related Products	dBET6 ARV-825 dBET1 ACBI1 ARV-771

Chemical Information, Storage & Stability

Molecular Weight	861.93	Formula	C₄₃H₄₆F₃N₇O₇S	Storage (From the date of receipt)	3 years -20°C powder
CAS No.	2490599-18-1	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC1=C(SC=N1)C2=CC=C(CNC(=O)C3CC(O)CN3C(=O)C(NC(=O)COCCOC4=CC=C(C=C4)C5=CC(=NC=N5)NC6=CC=C(OC(F)(F)F)C=C6)C(C)(C)C)C=C2

Solubility

In vitro
Batch:

DMSO : 100 mg/mL ( (116.01 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 50 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (5.80mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.830mg/ml (0.96mM)	Taking the 1 mL working solution as an example, add 50 μL of 16.6 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	BCR-ABL1 ^[1] E3 ligase ^[1]
In vitro	GMB-475 induces rapid proteasomal degradation and inhibition of downstream biomarkers, such as STAT5 in both human CML K562 cells and murine Ba/F3 cells expressing BCR-ABL1. This compound inhibits the proliferation of certain clinically relevant BCR-ABL1 kinase domain point mutants and further sensitizes Ba/F3 BCR-ABL1 cells to inhibition, while demonstrating no toxicity toward Ba/F3 parental cells.^[1]
References	https://pubmed.ncbi.nlm.nih.gov/31311809/

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Handling Instructions

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