| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 2mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
| Targets |
ERK1; ERK2
ASTX029 targets extracellular signal-regulated kinase (ERK1/2), a key component of the RAS-RAF-MEK-ERK MAPK signaling pathway. It inhibits ERK2 with an IC50 of 2.7 nM. The compound's dual mechanism—inhibiting both ERK catalytic activity and MEK-mediated ERK phosphorylation—represents a novel approach to MAPK pathway inhibition. |
|---|---|
| ln Vitro |
ASTX029 (96 h) has IC50 values ranging from 1.8 to 380 nM, which means that it suppresses the phosphorylation of human cancer cells with mutations that activate MAPK [2]. With IC50 values of 3.3 for A375 and HCT116 cells, respectively, ASTX029 (2 h) suppresses RSK phosphorylation. In A375 and HCT116 cells, ASTX029 (10 and 100 nM, 0-72 h) causes cell life cycle candles in the G1 phase and induces transplanting [2].
ASTX029 inhibits ERK2 with an IC50 of 2.7 nM and is selective for ERK over a panel of 465 kinases. In vitro, ASTX029 (96 h treatment) has IC50 values ranging from 1.8 to 380 nM, suppressing the phosphorylation of human cancer cells with mutations that activate MAPK. It inhibits ERK-dependent tumor cell proliferation and survival. |
| ln Vivo |
In tumor-bearing Colo205 (BRAFV600E-mottled colorectal cancer) tumors, ASTX029 (20–75 mg/kg, neck) inhibits tumor growth [2]. T1/2 was 2.9 hours, F (%) was 42%, and AUC for ASTX029 (5 mg/kg, neck, neck) was 1600 ng h/mL [3].
ASTX029 reduces tumor growth in A375, Calu-6, and COLO 205 mouse xenograft models. The compound's oral bioavailability and potent ERK inhibition make it a promising therapeutic for cancers driven by MAPK pathway activation, including BRAF- and RAS-mutant tumors where resistance to RAF and MEK inhibitors is common. |
| Enzyme Assay |
Cell-free kinase assays for ASTX029 utilize purified recombinant ERK2 enzyme and a suitable peptide substrate. The kinase reaction is performed in the presence of ATP and increasing concentrations of the compound. Phosphorylation of the substrate is quantified using radiometric or fluorescence-based detection. IC50 values are determined from concentration-response curves. Selectivity is assessed by screening against a panel of 465 kinases.
|
| Cell Assay |
Western Blot Analysis[2]
Cell Types: A375 and HCT116 Cell Tested Concentrations: 1 nM-100 nM Incubation Duration: 2 hrs (hours) Experimental Results: pRSK and pERK diminished. Apoptosis analysis[2] Cell Types: A375 and HCT116 Cell Tested Concentrations: 0-100 nM Incubation Duration: 0-72 hrs (hours) Experimental Results: Cell arrest in G1 phase. Cleaved PARP and Bim protein levels increased. Cells with MAPK pathway mutations (e.g., A375 melanoma, Calu-6 lung cancer, COLO 205 colorectal cancer) are treated with ASTX029 at various concentrations for up to 96 hours. ERK phosphorylation and downstream target phosphorylation are assessed by Western blot. Cell proliferation and viability are measured by MTT or CellTiter-Glo assays. IC50 values are determined from concentration-response curves. |
| Animal Protocol |
Animal/Disease Models: Colo205, A375, Calu-6, HCC44, HCT116 or MA-MEL-28 xenograft tumors in mice [2]
Doses: 75 mg/kg Route of Administration: po (po (oral gavage)) one time/day Experimental Results: In multiple tumor models Inhibit tumor growth. In vivo animal studies for ASTX029 are conducted in mouse xenograft models using A375, Calu-6, and COLO 205 tumor cell lines. The compound is administered orally at various doses. Tumor growth is measured over time, and tumor regression or growth inhibition is calculated. Pharmacodynamic markers (ERK phosphorylation in tumor tissue) are assessed. Body weight and clinical signs are monitored for tolerability. |
| ADME/Pharmacokinetics |
ASTX029 is orally bioavailable. As a small molecule (MW 584.04, formula C29H31ClFN5O5) with favorable drug-like properties, it has been characterized for PK parameters including Tmax, half-life, clearance, volume of distribution, and oral bioavailability in preclinical species. The compound is designed for once-daily oral administration in cancer therapy.
|
| Toxicity/Toxicokinetics |
Toxicity data for ASTX029 from preclinical studies indicate that ERK inhibition can cause dermatological and gastrointestinal toxicities similar to other MAPK pathway inhibitors. Standard genotoxicity, reproductive toxicity, and chronic toxicity studies have been conducted to support clinical development. The compound's selectivity for ERK over 465 kinases suggests a favorable off-target profile.
|
| References | |
| Additional Infomation |
Anhydrous beroterkib is the anhydrous form of beroterkib, an orally bioavailable inhibitor of extracellular signal-regulated kinases (ERK) 1 and 2 with potential antitumor activity. After administration, beroterkib specifically binds to and inhibits ERK1 and ERK2, thereby preventing activation of the mitogen-activated protein kinase (MAPK)/ERK-mediated signal transduction pathway. This leads to suppression of ERK-dependent tumor cell proliferation and survival. The MAPK/ERK pathway is frequently upregulated in various tumor cell types and plays a crucial role in tumor cell proliferation, differentiation, and survival.
ASTX029 (molecular formula C29H31ClFN5O5, MW 584.04) is a highly potent and selective dual-mechanism ERK inhibitor. It represents a novel approach to MAPK pathway inhibition by targeting both ERK catalytic activity and its phosphorylation by MEK. The compound is being developed for cancers with MAPK pathway activation, particularly those resistant to RAF and MEK inhibitors. |
| Molecular Formula |
C29H31CLFN5O5
|
|---|---|
| Molecular Weight |
584.0454
|
| Exact Mass |
583.2
|
| Elemental Analysis |
C, 59.64; H, 5.35; Cl, 6.07; F, 3.25; N, 11.99; O, 13.70
|
| CAS # |
2095719-92-7
|
| Related CAS # |
2095719-92-7
|
| PubChem CID |
129053037
|
| Appearance |
White to off-white solid powder
|
| LogP |
2.9
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
41
|
| Complexity |
900
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
C[C@H](C(=O)N[C@H](CO)C1=CC(=CC(=C1)F)OC)N2CC3=C(C2=O)C=C(C=C3)C4=NC(=NC=C4Cl)NC5CCOCC5
|
| InChi Key |
BVRGQPJKSKKGIH-PUAOIOHZSA-N
|
| InChi Code |
InChI=1S/C29H31ClFN5O5/c1-16(27(38)34-25(15-37)19-9-20(31)12-22(10-19)40-2)36-14-18-4-3-17(11-23(18)28(36)39)26-24(30)13-32-29(35-26)33-21-5-7-41-8-6-21/h3-4,9-13,16,21,25,37H,5-8,14-15H2,1-2H3,(H,34,38)(H,32,33,35)/t16-,25-/m1/s1
|
| Chemical Name |
(2R)-2-[5-[5-chloro-2-(oxan-4-ylamino)pyrimidin-4-yl]-3-oxo-1H-isoindol-2-yl]-N-[(1S)-1-(3-fluoro-5-methoxyphenyl)-2-hydroxyethyl]propanamide
|
| Synonyms |
ASTX-029; ASTX029; ASTX 029
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: 100~250 mg/mL (171.2~428.1 mM)
Ethanol: ~50 mg/mL (~85.6 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.56 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.08 mg/mL (3.56 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.56 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7122 mL | 8.5609 mL | 17.1218 mL | |
| 5 mM | 0.3424 mL | 1.7122 mL | 3.4244 mL | |
| 10 mM | 0.1712 mL | 0.8561 mL | 1.7122 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
