| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
ERK1; ERK2 |
|---|---|
| ln Vitro |
In various cell lines, ERK-IN-3 prevents the phosphorylation of ERK1/2 substrates like RSK1, FRA1, and Elk1[1]. Single-digit nanomolar antiproliferative activity of ERK-IN-3 is specific for cancer cell lines that are MAPK pathway dependent[1].
ASN007 inhibits ERK1/2 with an IC50 of 2 nM. It exhibits significant anti-proliferative activity against various tumor cells. The compound shows low single-digit nM IC50 values for ERK1/2 inhibition. ASN007 can be used for the research of cancers driven by RAS mutations, regardless of the mutation subtype. |
| ln Vivo |
At effective doses, ERK-IN-3 (daily p.o.) was well tolerated and inhibited tumor growth in several BRAF and KRAS mutant mouse xenograft models[1].
In vivo, ASN007 demonstrates robust antitumor activity. As an orally bioavailable compound, it can be administered orally for convenient dosing. The compound is under clinical investigation as a promising targeted therapy for MAPK-driven malignancies. ASN007 has shown efficacy in preclinical models of cancers driven by RAS mutations. Combination treatment strategies are being explored. |
| Enzyme Assay |
ERK1/2 kinase activity assays are performed using recombinant ERK1 or ERK2 enzymes and appropriate peptide substrates (e.g., MBP or Elk-1) in the presence of ATP. The assay typically employs a fluorescence-based or radiometric format to measure kinase activity. ASN007 is incubated with the enzyme, substrate, and ATP in assay buffer for 30-60 minutes. The reaction is stopped and product formation is quantified. IC50 values are calculated from concentration-response curves.
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| Cell Assay |
Cancer cell lines with RAS mutations or MAPK pathway activation are seeded in multi-well plates and treated with varying concentrations of ASN007 for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. ERK1/2 phosphorylation (p-ERK) and downstream signaling markers (p-AKT, p-RSK) are assessed by Western blot. Cell proliferation is assessed by BrdU incorporation or colony formation assays. The compound's anti-proliferative activity is evaluated across a panel of tumor cell lines.
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| Animal Protocol |
In vivo efficacy is evaluated in mouse xenograft models using human cancer cell lines with RAS mutations or MAPK pathway activation. Tumor-bearing mice are treated with ASN007 orally at various doses. Tumor volumes are measured every 2-3 days. Pharmacodynamic markers such as ERK1/2 phosphorylation are measured in tumor tissues to confirm target engagement. Body weight and clinical signs are monitored for tolerability. The compound's antitumor activity is assessed by tumor growth inhibition.
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| ADME/Pharmacokinetics |
ASN007 is orally bioavailable with favorable pharmacokinetic properties. It has molecular formula C22H25ClFN7O2 and molecular weight 473.93. The compound is soluble in DMSO (100 mg/mL). For in vivo studies, it can be formulated in 0.5% Methyl cellulose/0.5% Tween-80 in saline (suspension, 6.67 mg/mL) or 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline (clear solution, ≥2.08 mg/mL).
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies for ASN007 are ongoing as part of clinical development. As an ERK1/2 inhibitor targeting the MAPK pathway, potential toxicities may include skin rash, gastrointestinal effects, and other effects associated with MAPK pathway inhibition. The compound has been evaluated in preclinical models with acceptable tolerability. Standard safety pharmacology, genotoxicity, and repeated-dose toxicity studies are being conducted for regulatory approval.
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| References | |
| Additional Infomation |
ERAS-007, an ERK1/2 inhibitor, is an orally bioavailable inhibitor of extracellular signal-regulated kinases 1 (ERK1) and 2 (ERK2) with potential antitumor activity. After oral administration, ERAS-007 specifically binds to and inhibits the serine/threonine protein kinase activity of ERK1 and ERK2, thereby preventing phosphorylation of ERK1/2 substrates and 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, also known as the RAS/RAF/MEK/ERK pathway, is overactivated in various tumor cell types due to mutations in upstream target genes. It plays a crucial role in tumor cell proliferation, differentiation, and survival.
ASN007 is also known as ERK-IN-3. It is a potent and orally active inhibitor of ERK1/2 with low single-digit nM IC50 values. The compound can be used for the research of cancers driven by RAS mutations. ASN007 is under clinical investigation as a promising targeted therapy for MAPK-driven malignancies. |
| Molecular Formula |
C22H25CLFN7O2
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|---|---|
| Molecular Weight |
473.931006193161
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| Exact Mass |
473.17
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| Elemental Analysis |
C, 55.75; H, 5.32; Cl, 7.48; F, 4.01; N, 20.69; O, 6.75
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| CAS # |
2055597-12-9
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| Related CAS # |
ASN007 benzenesulfonate;2055597-39-0
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| PubChem CID |
124122366
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| Appearance |
White to light yellow solid powder
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| LogP |
2.3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
644
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=CN=C(N=C1N2C=C(N=C2)C(=O)N[C@H](CN)C3=CC(=CC(=C3)Cl)F)NC4CCOCC4
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| InChi Key |
PWHIUQBBGPGFFV-GOSISDBHSA-N
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| InChi Code |
InChI=1S/C22H25ClFN7O2/c1-13-10-26-22(28-17-2-4-33-5-3-17)30-20(13)31-11-19(27-12-31)21(32)29-18(9-25)14-6-15(23)8-16(24)7-14/h6-8,10-12,17-18H,2-5,9,25H2,1H3,(H,29,32)(H,26,28,30)/t18-/m1/s1
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| Chemical Name |
N-[(1S)-2-amino-1-(3-chloro-5-fluorophenyl)ethyl]-1-[5-methyl-2-(oxan-4-ylamino)pyrimidin-4-yl]imidazole-4-carboxamide;benzenesulfonic acid
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| Synonyms |
ASN007; ASN 007; ASN-007
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 95 ~200 mg/mL (200.5~422 mM)
Ethanol: ~95 mg/mL (~200.5 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.39 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 (4.39 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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 (4.39 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 6.67 mg/mL (14.07 mM) in 0.5% MC 0.5% Tween-80 (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1100 mL | 10.5501 mL | 21.1002 mL | |
| 5 mM | 0.4220 mL | 2.1100 mL | 4.2200 mL | |
| 10 mM | 0.2110 mL | 1.0550 mL | 2.1100 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03415126 | Completed | Drug: ASN007: ascending doses Drug: ASN007 RD |
Cancer Malignancy |
Asana BioSciences | January 19, 2018 | Phase 1 |
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