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MedKoo Cat#: 463912 | Name: ASTX-029
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

ASTX029 is a highly potent and selective dual-mechanism ERK inhibitor. ASTX029 inhibits both ERK catalytic activity and the phosphorylation of ERK itself by MEK, despite not directly inhibiting MEK activity. ASTX029 preferentially inhibited the proliferation of MAPK-activated cell lines, including those with BRAF or RAS mutations. ASTX029 also demonstrated activity in both in vitro and in vivo models of acquired resistance to MAPK pathway inhibitors.

Chemical Structure

ASTX-029
ASTX-029
CAS#2095719-92-7

Theoretical Analysis

MedKoo Cat#: 463912

Name: ASTX-029

CAS#: 2095719-92-7

Chemical Formula: C29H31ClFN5O5

Exact Mass: 583.1998

Molecular Weight: 584.05

Elemental Analysis: C, 59.64; H, 5.35; Cl, 6.07; F, 3.25; N, 11.99; O, 13.70

Price and Availability

Size Price Availability Quantity
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,350.00 Ready to ship
500mg USD 2,650.00 Ready to ship
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Related CAS #
No Data
Synonym
ASTX-029; ASTX029; ASTX 029; beroterkibum; beroterkib
IUPAC/Chemical Name
(R)-2-(6-(5-chloro-2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-1-oxoisoindolin-2-yl)-N-((S)-1-(3-fluoro-5-methoxyphenyl)-2-hydroxyethyl)propanamide
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
SMILES Code
ClC(C(C1=CC=C2C(C(N([C@H](C)C(N[C@H](CO)C3=CC(OC)=CC(F)=C3)=O)C2)=O)=C1)=N4)=CN=C4NC5CCOCC5
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Biological target:
ASTX-029 is an inhibitor of the extracellular signal-regulated kinases (ERK) 1 and 2, with potential antineoplastic activity that inhibits ERK-dependent tumor cell proliferation and survival.
In vitro activity:
The dual mechanism of ASTX029 was investigated further in cell lines with activating mutations in the MAPK pathway. Following a 2-hour treatment, ASTX029 inhibited the phosphorylation of RSK in a dose-dependent manner in both A375 (BRAFV600E-mutant melanoma) and HCT116 (KRASG13D-mutant colorectal) cells with IC50 values of 3.3 and 4 nmol/L, respectively. In agreement with the observations in cell-free assays, 2-hour treatment of A375 and HCT116 cells with ASTX029 resulted in a decrease in pERK levels with a maximum inhibition of 93% and 94% relative to control levels, respectively. ASTX029 treatment resulted in a dose-dependent cell-cycle arrest in the G1-phase. An increase in the fraction of cells in the sub-G1-phase along with an increase in apoptotic markers such as cleaved PARP and Bim suggested compound treatment induced apoptosis. Reference: Mol Cancer Ther. 2021 Oct;20(10):1757-1768. https://pubmed.ncbi.nlm.nih.gov/34330842/
In vivo activity:
Following a single oral dose of 75 mg/kg ASTX029 to mice bearing Colo205 (BRAFV600E-mutant colorectal) tumor xenografts, maximal plasma, and tumor exposure was reached within 0.5 hours and was detectable up to 24 hours. In addition to inhibiting ERK catalytic activity, ASTX029 treatment also resulted in a decrease in tumor pERK levels. This was maximal at 1-hour post-dose, with pERK levels reduced to 35% of control. Levels then increased with time and were fully restored to untreated levels by 24 hours. Following ASTX029 treatment an increase in Bim, cleaved caspase 3 and cleaved PARP was observed, suggesting induction of apoptosis in the tumors. Once daily oral administration of ASTX029 to Colo205 (BRAFV600E-mutant colorectal cancer) tumor-bearing mice significantly inhibited tumor growth in a dose-dependent manner over the range of 25 to 75 mg/kg, with tumor regressions observed at 75 mg/kg. Administering ASTX029 at 150 mg/kg every other day also resulted in tumor regression (P < 0.0001). Reference: Mol Cancer Ther. 2021 Oct;20(10):1757-1768. https://pubmed.ncbi.nlm.nih.gov/34330842/
Solvent mg/mL mM comments
Solubility
DMSO 57.5 98.46
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 584.05 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Munck JM, Berdini V, Bevan L, Brothwood JL, Castro J, Courtin A, East C, Ferraldeschi R, Heightman TD, Hindley CJ, Kucia-Tran J, Lyons JF, Martins V, Muench S, Murray CW, Norton D, O'Reilly M, Reader M, Rees DC, Rich SJ, Richardson CJ, Shah AD, Stanczuk L, Thompson NT, Wilsher NE, Woolford AJ, Wallis NG. ASTX029, a Novel Dual-mechanism ERK Inhibitor, Modulates Both the Phosphorylation and Catalytic Activity of ERK. Mol Cancer Ther. 2021 Oct;20(10):1757-1768. doi: 10.1158/1535-7163.MCT-20-0909. Epub 2021 Jul 30. PMID: 34330842.
In vitro protocol:
1. Munck JM, Berdini V, Bevan L, Brothwood JL, Castro J, Courtin A, East C, Ferraldeschi R, Heightman TD, Hindley CJ, Kucia-Tran J, Lyons JF, Martins V, Muench S, Murray CW, Norton D, O'Reilly M, Reader M, Rees DC, Rich SJ, Richardson CJ, Shah AD, Stanczuk L, Thompson NT, Wilsher NE, Woolford AJ, Wallis NG. ASTX029, a Novel Dual-mechanism ERK Inhibitor, Modulates Both the Phosphorylation and Catalytic Activity of ERK. Mol Cancer Ther. 2021 Oct;20(10):1757-1768. doi: 10.1158/1535-7163.MCT-20-0909. Epub 2021 Jul 30. PMID: 34330842.
In vivo protocol:
1. Munck JM, Berdini V, Bevan L, Brothwood JL, Castro J, Courtin A, East C, Ferraldeschi R, Heightman TD, Hindley CJ, Kucia-Tran J, Lyons JF, Martins V, Muench S, Murray CW, Norton D, O'Reilly M, Reader M, Rees DC, Rich SJ, Richardson CJ, Shah AD, Stanczuk L, Thompson NT, Wilsher NE, Woolford AJ, Wallis NG. ASTX029, a Novel Dual-mechanism ERK Inhibitor, Modulates Both the Phosphorylation and Catalytic Activity of ERK. Mol Cancer Ther. 2021 Oct;20(10):1757-1768. doi: 10.1158/1535-7163.MCT-20-0909. Epub 2021 Jul 30. PMID: 34330842.
1: Heightman TD, Berdini V, Bevan L, Buck IM, Carr MG, Courtin A, Coyle JE, Day JEH, East C, Fazal L, Griffiths-Jones CM, Howard S, Kucia-Tran J, Martins V, Muench S, Munck JM, Norton D, O'Reilly M, Palmer N, Pathuri P, Peakman TM, Reader M, Rees DC, Rich SJ, Shah A, Wallis NG, Walton H, Wilsher NE, Woolford AJ, Cooke M, Cousin D, Onions S, Shannon J, Watts J, Murray CW. Discovery of ASTX029, A Clinical Candidate Which Modulates the Phosphorylation and Catalytic Activity of ERK1/2. J Med Chem. 2021 Aug 26;64(16):12286-12303. doi: 10.1021/acs.jmedchem.1c00905. Epub 2021 Aug 13. PMID: 34387469. 2: Munck JM, Berdini V, Bevan L, Brothwood JL, Castro J, Courtin A, East C, Ferraldeschi R, Heightman TD, Hindley CJ, Kucia-Tran J, Lyons JF, Martins V, Muench S, Murray CW, Norton D, O'Reilly M, Reader M, Rees DC, Rich SJ, Richardson CJ, Shah AD, Stanczuk L, Thompson NT, Wilsher NE, Woolford AJ, Wallis NG. ASTX029, a Novel Dual-mechanism ERK Inhibitor, Modulates Both the Phosphorylation and Catalytic Activity of ERK. Mol Cancer Ther. 2021 Oct;20(10):1757-1768. doi: 10.1158/1535-7163.MCT-20-0909. Epub 2021 Jul 30. PMID: 34330842.