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ONO-8430506
AOB11203
CAS 1354805-08-5
Chemical Name: 4-(2-(9-(4-Fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrrolo[2,3-b:5,4-c']dipyridin-7-yl)-2-oxoethyl)bicyclo[2.2.1]heptane-1-carboxylic acid
6000 Items
Quantity Discount Table - Order More To Get More Price Discount
| Quantity | mg | Unit Price ($/mg or $/Unit) | Final Price |
|---|---|---|---|
| 1 | 5 | $17.85 | Total: $89.25 |
| 1 | 10 | $15.12 | Total: $151.20 |
| 1 | 25 | $12.81 | Total: $320.25 |
| 1 | 50 | $10.92 | Total: $546.00 |
| 1 | 100 | $9.45 | Total: $945.00 |
Overview
Novel Autotaxin Inhibitor That Enhances the Antitumor Effect of Paclitaxel in a Breast Cancer Model
Mechanism of action
Autotaxin is a secreted lysophospholipase D enzyme that converts lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), a bioactive lipid mediator. PubMed+4wjon.org+4
LPA binds to multiple G-protein-coupled receptors (LPAR1-6), triggering signalling pathways involved in cell proliferation, motility, survival, inflammation, and other functions. American Chemical Society Publications+2wjon.org+2
ONO-8430506 inhibits autotaxin, thereby reducing LPA production. For example, it has IC₅₀ values around ~4.5-5 nM in assays measuring LPC conversion, and ~10 nM in human plasma/ex vivo assays. Synapse
The downstream effect of reducing LPA: less activation of LPA-receptor signalling, which can reduce proliferation/migration/inflammation that is often up-regulated in disease contexts. For example, in primary chondrocytes, addition of ONO-8430506 (an ATX inhibitor) led to smaller cell sizes and reduced proliferation. Nature
Key pre-clinical findings
ONO-8430506 has good oral bioavailability (in rats, dogs, monkeys) and pharmacokinetic profiles suitable for in-vivo use.
In rodent cancer models (breast cancer models), ONO-8430506 slowed tumour growth and decreased lung metastasis by ~60% in certain models. PubMed+2
It also enhanced the antitumour effect of standard chemotherapy agent Paclitaxel in a breast cancer model. PubMed+1
In other disease contexts, because LPA signalling is implicated in inflammation, fibrosis, pain, etc., inhibition of autotaxin may be beneficial. For example: urethral tension reduction (via ATX → LPA signalling) was observed in animals treated with ONO-8430506.
Therapeutic implications & current status
The compound is still in the pre-clinical stage (as of the latest accessible literature) and is described in the literature for research use only.
Because the ATX–LPA axis is implicated in a variety of pathological states (cancer, fibrosis, inflammation, neuropathic pain) this inhibitor is of interest as a therapeutic probe and potential drug-lead. For example, a review article notes ONO-8430506 in context of ATX inhibition for cancer therapy. wjon.org+1
No publicly available information (in the sources we located) indicates that ONO-8430506 has progressed to human clinical trials (at least as of the publications noted).
Chemical Properties
| Molecular Formula | C27H28FN3O3 |
| Molecular Weight | 461.54 |
| CAS Numbers | 1354805-08-5 |
| Solubility | DMSO |
| Purity | 98% by HPLC |
| IUPAC/Chemical Name | 4-(2-(9-(4-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrrolo[2,3-b:5,4-c']dipyridin-7-yl)-2-oxoethyl)bicyclo[2.2.1]heptane-1-carboxylic acid |
| InChl Key | SGSFONPFVRRJLS-UHFFFAOYSA-N |
| InChl Code | InChI=1S/C27H28FN3O3/c28-19-5-3-18(4-6-19)15-31-22-16-30(13-7-20(22)21-2-1-12-29-24(21)31)23(32)14-26-8-10-27(17-26,11-9-26)25(33)34/h1-6,12H,7-11,13-17H2,(H,33,34) |
| SMILES Code | O=C(C1(C2)CCC2(CC(N(C3)CCC4=C3N(CC5=CC=C(F)C=C5)C6=NC=CC=C64)=O)CC1)O |
Storage and Handling
0°C (short term), -20°C (long term), desiccated
Synonyms
ONO-8430506; ONO 8430506; ONO8430506
References
1) Saga H, Ohhata A, Hayashi A, et al. A novel highly potent autotaxin/ENPP2 inhibitor produces prolonged decreases in plasma lysophosphatidic acid formation in vivo and regulates urethral tension. PLoS One. 2014;9(4):e93230. Published 2014 Apr 18. doi:10.1371/journal.pone.0093230