CG428

Name: CG428
Brand: MedChemExpress
SKU: HY-137465
Rating: 4.5 (0 reviews)

Cat. No.: HY-137465 Purity: 98.18%: Data Sheet
COA

SDS
Handling Instructions
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CG428 is a potent and selective CRBN-dependent tropomyosin receptor kinase (TRK) PROTAC degrader that has anti-tumor activity. CG428 reduces levels of the tropomyosin 3 TPM3-TRKA fusion protein in KM12 colorectal carcinoma cells (DC₅₀ = 0.36 nM) and inhibits downstream PLCγ1 phosphorylation (IC₅₀ = 0.33 nM). CG428 has a higher binding affinity for TRKA than TRKB and TRKC (Kd = 1 nM, 28 nM and 4.2 nM, respectively). CG428 can be used for the research of colorectal carcinoma.
(Pink: Trk Receptor ligand (HY-118271); Blue: Cereblon ligand (HY-41547); Black: linker (HY-W067489)).

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

CG428 Chemical Structure

CAS No. : 2412055-93-5

Size	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	In-stock	Estimated Time of Arrival: December 31
Solid
1 mg	In-stock	Estimated Time of Arrival: December 31
5 mg	In-stock	Estimated Time of Arrival: December 31
10 mg	In-stock	Estimated Time of Arrival: December 31
25 mg	In-stock	Estimated Time of Arrival: December 31
50 mg	Get quote
100 mg	Get quote

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von Hippel-Lindau (VHL) Cereblon MDM2 cIAP1

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TrkA TrkB TrkC Trk

Biological Activity
Purity & Documentation
References
Customer Review

Description

CG428 is a potent and selective CRBN-dependent tropomyosin receptor kinase (TRK) PROTAC degrader that has anti-tumor activity. CG428 reduces levels of the tropomyosin 3 TPM3-TRKA fusion protein in KM12 colorectal carcinoma cells (DC₅₀ = 0.36 nM) and inhibits downstream PLCγ1 phosphorylation (IC₅₀ = 0.33 nM). CG428 has a higher binding affinity for TRKA than TRKB and TRKC (Kd = 1 nM, 28 nM and 4.2 nM, respectively). CG428 can be used for the research of colorectal carcinoma^[1]. (Pink: Trk Receptor ligand (HY-118271); Blue: Cereblon ligand (HY-41547); Black: linker (HY-W067489)).

IC₅₀ & Target^[1]

TrkA

1 nM (Kd)

TrkC

4.2 nM (Kd)

TrkB

28 nM (Kd)

Cereblon

Cellular Effect

Cell Line	Type	Value	Description	References
KM12	IC₅₀	52 nM Compound: 6; CG428	Antiproliferative activity against human KM12 cells assessed as reduction in cell viability measured after 3 days by Celltiter-Glo assay Antiproliferative activity against human KM12 cells assessed as reduction in cell viability measured after 3 days by Celltiter-Glo assay	[PMID: 33058680]

In Vitro

CG428 binds with high affinity to recombinant TRKA, TRKB, and TRKC kinases, with K_d values of 1.0, 28.0 and 4.2 nM^[1].
CG428 degrades endogenous TPM3-TRKA fusion protein (DC50 = 0.36 nM) and inhibits PLCγ1 phosphorylation (IC₅₀ = 0.33 nM) in KM12 cells^[1].
CG428 potently degrades endogenous wild-type TRKA in HEL cells with a DC₅₀ of 2.23 nM^[1].
CG428 (0.7-500 nM; 6 h) exhibits reduced potency for degradation of ectopically expressed AGBL4-TRKB and ETV6-TRKC fusion protein in KM12 cells, with a hook effect at high concentrations^[1].
CG428 potently inhibits the growth of KM12 cells with an IC₅₀ of 2.9 nM^[1].

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

Western Blot Analysis^[1]

Cell Line:	KM12 human colorectal carcinoma cells
Concentration:	0.04, 0.12, 0.4, 1.1, 3.3, 10, 30 nM
Incubation Time:	6 h
Result:	Induced potent degradation of TPM3-TRKA with a DC₅₀ of 0.36 ± 0.06 nM. Inhibited downstream PLCγ1 phosphorylation with an IC₅₀ of 0.33 ± 0.06 nM. Caused 96 ± 3% TPM3-TRKA degradation at 10 nM. Caused 82 ± 2% TPM3-TRKA degradation at 1 nM. Caused 46 ± 6% TPM3-TRKA degradation at 0.1 nM.

Parmacokinetics

Species	Dose	Route	C_max	T_max	T_1/2
Mice^[1]	10 mg/kg	i.p.	1640 nM	1 h	0.9 h

In Vivo

CG428 (10 mg/kg; i.p.; single dose) demonstrates good plasma exposure in male ICR mice following a single 10 mg/kg intraperitoneal administration, with concentrations remaining well above its in vitro DC₅₀ up to 8 h post dosing^[1].

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

Animal Model:	ICR (male)^[1]
Dosage:	10 mg/kg
Administration:	i.p.; single dose
Result:	Reached a maximum plasma concentration of 1640 ± 120 nM at 1 h post dosing. Plasma concentration was 12.4 ± 13.6 nM at 8 h post dosing. Exhibited a half-life of 0.9 h.

Clinical Trial

Molecular Weight

814.86

Formula

C₄₃H₄₃FN₁₀O₆

CAS No.

2412055-93-5

Appearance

Solid

Color

Light yellow to yellow

SMILES

O=C1N(C(CC2)C(NC2=O)=O)C(C3=C1C=CC=C3NCCOCCC(N4CCN(C5=NC(C6=CN=C7C=CC(N8[C@@H](C9=CC=CC(F)=C9)CCC8)=NN76)=CC=C5)CC4)=O)=O

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

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL (122.72 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	1.2272 mL	6.1360 mL	12.2720 mL
5 mM	0.2454 mL	1.2272 mL	2.4544 mL
10 mM	0.1227 mL	0.6136 mL	1.2272 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, 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
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)

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In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

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(per animal)

μL

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

Calculation results:

Working solution concentration: mg/mL

Purity & Documentation

Purity: 98.26%

Select Batch:

Data Sheet (272 KB) SDS (251 KB)

COA (246 KB) HNMR (188 KB) CNMR (178 KB) RP-HPLC (170 KB) LCMS (170 KB)

Handling Instructions (2659 KB)

References

[1]. Chen L, et al. Discovery of First-In-Class Potent and Selective Tropomyosin Receptor Kinase Degraders. J Med Chem. 2020;63(23):14562-14575. [Content Brief]

Complete Stock Solution Preparation Table

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

DMSO	1 mM	1.2272 mL	6.1360 mL	12.2720 mL	30.6801 mL
	5 mM	0.2454 mL	1.2272 mL	2.4544 mL	6.1360 mL
	10 mM	0.1227 mL	0.6136 mL	1.2272 mL	3.0680 mL
	15 mM	0.0818 mL	0.4091 mL	0.8181 mL	2.0453 mL
	20 mM	0.0614 mL	0.3068 mL	0.6136 mL	1.5340 mL
	25 mM	0.0491 mL	0.2454 mL	0.4909 mL	1.2272 mL
	30 mM	0.0409 mL	0.2045 mL	0.4091 mL	1.0227 mL
	40 mM	0.0307 mL	0.1534 mL	0.3068 mL	0.7670 mL
	50 mM	0.0245 mL	0.1227 mL	0.2454 mL	0.6136 mL
	60 mM	0.0205 mL	0.1023 mL	0.2045 mL	0.5113 mL
	80 mM	0.0153 mL	0.0767 mL	0.1534 mL	0.3835 mL
	100 mM	0.0123 mL	0.0614 mL	0.1227 mL	0.3068 mL

CG428 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:

CG4282412055-93-5CG 428CG-428PROTACsTrk ReceptorTropomyosin related kinase receptorETV6-TRKC fusion proteincereblonTPM3-TRKA fusion proteinPLCγ1colorectal carcinoma cellsKM12 cellsAGBL4-TRKB fusion proteinubiquitin-proteasome systemHEL cellsInhibitorinhibitorinhibit

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CG428

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CG428 Related Antibodies

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Customer Review

CG428 Related Antibodies

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Complete Stock Solution Preparation Table

CG428 Related Classifications

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