Art. -Nr.: HY-178061

APS03118

APS03118 is an orally active, potent and selective rearranged during transfection (RET) inhibitor. APS03118 broadly inhibits RET fusions and mutations (including G810, V804, L730, and Y806 variants), with IC₅₀ values predominantly below 1 nM (0.095 nM for WT; ranging from 0.00438 to 5.72 nM for mutants), and demonstrates marked superiority against RET G810 mutations. APS03118 inhibits the entire RET signaling pathway (including RET, Shc, and ERK1/2), with >20-fold selectivity over most off-target kinases (except FLT3 and YES). APS03118 induces complete tumor regression in KIF5B-RET and CCDC6-RET V804 M patient derived xenografts (PDXs) and significantly prolongs survival in an intracranial CCDC6-RET metastasis mice model. APS03118 can be used for selective RET inhibitor (SRI)-resistant, RET-driven cancer research.

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Reinheit: 98.99%
CAS. Nr.: 2598870-24-5
Formel: C₂₇H₂₈N₈O₂
Molecular Weight:496.56

Speicherung:

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

APS03118 Chemical Structure

CAS. Nr.: 2598870-24-5

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Use of MCE Products

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

Biologische Aktivität
- Beschreibung
- In Vitro
- Parmacokinetics
- In Vivo
- Clinical Trial
Chemical Information
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

Alle ERK Isoform-spezifische Produkte anzeigen :

In Vitro

APS03118 (compound 5) shows markedly superior activity against the solvent-front RET G810 mutation compared to Selpercatinib (HY-114370) and Pralsetinib (HY-112301)^[1].
APS03118 exhibits superior efficacy against resistant RET mutations in engineered models (solvent-front and gatekeeper) and also demonstrates potent antiproliferative activity comparable to Pralsetinib and Selpercatinib in a native RET fusion-positive LC2/ad lung cancer cells (IC₅₀ = 10.08 nM)^[1].
APS03118 (0-3000 nM) inhibits RET autophosphorylation in Ba/F3 KIF5B-RET, Ba/F3 KIF5B-RET V804M, Ba/F3 KIF5B-RET G810R, and Ba/F3 KIF5B-RET M918T cells with IC₅₀ values of 1.91, 1.18, 14.66, and 2.28 nM^[1].
APS03118 (0-1000 nM, 1.5 h) potently inhibits the entire RET signaling pathway (including RET, Shc, and ERK1/2) in TT-RET C634W cells at low nanomolar concentrations^[1].

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

Western Blot Analysis^[1]

Cell Line:

TT-RET C634W cells
Concentration:

0, 1, 10, 100, and 1000 nM
Incubation Time:

1.5 h
Result:

Almost abolished the phosphorylation of RET, Shc and ERK1/2 at 10 nM, whereas Selpercatinib and Pralsetinib only partially inhibited it.
Inhibited the phosphorylation of RET, Shc, and ERK1/2 at concentrations below 10 nM.

Parmacokinetics

Species	Dose	Route	T_1/2	AUC_0-last	C_max	T_max	F	AUC_last	V_d	CL
Dog^[1]	10 mg/kg	p.o.	1.98 h	1106 ng·h/mL	322 ng/mL	1.67 h	18.0 %	/	/	/
Dog^[1]	2 mg/kg	i.v.	1.34 h	/	/	/	/	1228 ng·h/mL	3.16 L/kg	26.9 mL/min/kg
Monkey^[1]	2 mg/kg	i.v.	2.23 h	/	/	/	/	1965 ng·h/mL	3.62 L/kg	17.3 mL/min/kg
Monkey^[1]	2 mg/kg	p.o.	2.69 h	797 ng·h/mL	122 ng/mL	4.00 h	38.9 %	/	/	/
Rat^[1]	5 mg/kg	i.v.	2.68 h	/	/	/	/	21798 ng·h/mL	0.849 L/kg	4.26 mL/min/kg
Rat^[1]	5 mg/kg	p.o.	2.72 h	13843 ng·h/mL	2522 ng/mL	4.00 h	67.3 %	/	/	/

In Vivo

APS03118 (3, 10 and 30 mg/kg, p.o., BID for 28 days) shows potent anti-tumor effects in KIF5B-RET and CCDC6-RET V804M PDX mice models^[1].
APS03118 (10 and 30 mg/kg, p.o., BID for 90 days) eliminates intracranial tumors and prolongs survival in an intracranial CCDC6-RET mice metastasis model^[1].
APS03118 (10 and 30 mg/kg, p.o., BID for 14 and 15 days) inhibits tumor growth in Ba/F3 KIF5B-RET G810R and Ba/F3 KIF5B-RET V804M CDX mice models^[1].

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

Animal Model:

Female BALB/c nude mice (6-8 weeks) subcutaneously implanted with KIF5B-RET tumors^[1]
Dosage:

3, 10 and 30 mg/kg
Administration:

p.o., BID for 28 days
Result:

Inhibited tumor growth in a dose-dependent manner, with TGI of 85, 107, and 109% at 3, 10, and 30 mg/kg, respectively.
Significantly reduced tumor volumes on day 17 compared to the vehicle.
Achieved complete tumor regression at 10 and 30 mg/kg at the study end point, matching the efficacy of Selpercatinib at its 10 mg/kg dose.
Revealed no significant body weight changes.

Animal Model:

Female BALB/c nude mice (6-8 weeks) subcutaneously implanted with CCDC6-RET V804M tumors^[1]
Dosage:

3, 10 and 30 mg/kg
Administration:

p.o., BID for 28 days
Result:

Achieved tumor growth inhibition of 88, 99, and 100%, at 3, 10, and 30 mg/kg, respectively.
Reduced tumor volumes in all tested group.
Reduced tumor size at 3 and 10 mg/kg, with efficacy comparable to Selpercatinib at its 10 mg/kg dose.
Revealed no significant body weight changes.

Animal Model:

Female BALB/c nude mice (6-8 weeks) intracranially implanted with CCDC6-RET tumors into the brain^[1]
Dosage:

10 and 30 mg/kg
Administration:

p.o., BID for 90 days
Result:

Significantly prolonged the survival time and demonstrated a 100% survival rate at a dose of 10 mg/kg.
Induced complete regression of brain tumors at 10 and 30 mg/kg.

Animal Model:

Female BALB/c nude mice (6-8 weeks) subcutaneously injected with Ba/F3 KIF5B-RET G810R cells^[1]
Dosage:

10 and 30 mg/kg
Administration:

p.o., BID for 15 days
Result:

Induced potent tumor growth inhibition with a TGI of 90% at 30 mg/kg, while Selpercatinib achieved only 48% TGI at the same dose.
Exhibited greater efficacy than Selpercatinib in slowing the growth of Ba/F3 KIF5B-RET G810R allograft tumors at the same dose.
Exhibited excellent tolerability at 10 and 30 mg/kg, with no significant body weight loss or apparent abnormalities in mice.
Significantly reduced tumor volume compared to control on day 11.

Animal Model:

Female BALB/c nude mice (6-8 weeks) subcutaneously injected with Ba/F3 KIF5B-RET V804M cells^[1]
Dosage:

10 mg/kg
Administration:

p.o., BID for 14 days
Result:

Achieved considerably higher TGI rates of 61% compared to Selpercatinib (10 mg/kg, p.o., BID; TGI = 48%).
Was well-tolerated with no significant body weight loss in mice compared to the vehicle group during the treatment period.

Clinical Trial

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

Chemical Information

CAS. Nr. 2598870-24-5
Appearance Solid
Molecular Weight 496.56
Formel C₂₇H₂₈N₈O₂
Color White to off-white
SMILES

CCOC1=CN2NC3=NN=CC3=C2C(C4=CC=C(N5CC6N(C(C6)C5)CC7=CN=C(C=C7)OC)N=C4)=C1
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

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

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 100 mg/mL (201.39 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

2.0139 mL

10.0693 mL

20.1386 mL

5 mM

0.4028 mL

2.0139 mL

4.0277 mL

10 mM

0.2014 mL

1.0069 mL

2.0139 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.

Molaritätsrechner

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

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

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 (5.03 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 (5.03 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 (5.03 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 Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

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

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (285 KB)
SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 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)

Verweise

[1]. Zhong J, et al. Discovery of APS03118, a Potent and Selective Next-Generation RET Inhibitor with a Novel Kinase Hinge Scaffold. J Med Chem. 2025 Sep 25;68(18):19536-19553. [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	2.0139 mL	10.0693 mL	20.1386 mL	50.3464 mL
	5 mM	0.4028 mL	2.0139 mL	4.0277 mL	10.0693 mL
	10 mM	0.2014 mL	1.0069 mL	2.0139 mL	5.0346 mL
	15 mM	0.1343 mL	0.6713 mL	1.3426 mL	3.3564 mL
	20 mM	0.1007 mL	0.5035 mL	1.0069 mL	2.5173 mL
	25 mM	0.0806 mL	0.4028 mL	0.8055 mL	2.0139 mL
	30 mM	0.0671 mL	0.3356 mL	0.6713 mL	1.6782 mL
	40 mM	0.0503 mL	0.2517 mL	0.5035 mL	1.2587 mL
	50 mM	0.0403 mL	0.2014 mL	0.4028 mL	1.0069 mL
	60 mM	0.0336 mL	0.1678 mL	0.3356 mL	0.8391 mL
	80 mM	0.0252 mL	0.1259 mL	0.2517 mL	0.6293 mL
	100 mM	0.0201 mL	0.1007 mL	0.2014 mL	0.5035 mL

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APS03118

Alle ERK Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

APS03118 Related Classifications

HY-178061 Related Classifications

Bioz