Ro 08-2750 is a novel, potent, selective, and reversible non-peptide inhibitor of Nerve growth factor (NGF), binding to the NGF dimer with a KD of ~ 1 μM. It inhibits TRKA binding to p75NTR but not NGF. With an IC50 of 2.7 μM, Ro 08-2750 is a selective MSI RNA-binding activity inhibitor. NGF may have negative effects on IVD cells' catabolic/anabolic balance and matrix turnover activity, which could accelerate the degeneration of IVDs. The IVD degeneration process' progressive tissue breakdown may be ameliorated and the pain may be reduced by anti-NGF therapy.
Physicochemical Properties
| Molecular Formula | C13H10N4O3 |
| Molecular Weight | 270.2435 |
| Exact Mass | 270.075 |
| Elemental Analysis | C, 57.78; H, 3.73; N, 20.73; O, 17.76 |
| CAS # | 37854-59-4 |
| Related CAS # | 37854-59-4 |
| PubChem CID | 17756791 |
| Appearance | Orange to red solid powder |
| Density | 1.6±0.1 g/cm3 |
| Index of Refraction | 1.754 |
| LogP | -0.81 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 1 |
| Heavy Atom Count | 20 |
| Complexity | 554 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=CC1C(C)=CC2=C(N(C3=NC(=O)NC(=O)C3=N2)C)C=1 |
| InChi Key | JDEMVNYMYPJJIM-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C13H10N4O3/c1-6-3-8-9(4-7(6)5-18)17(2)11-10(14-8)12(19)16-13(20)15-11/h3-5H,1-2H3,(H,16,19,20) |
| Chemical Name | 7,10-dimethyl-2,4-dioxobenzo[g]pteridine-8-carbaldehyde |
| Synonyms | Ro-08-2750; Ro 082750; Ro -082750; Ro 08-2750; Ro08-2750; Ro082750 |
| 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) |
Biological Activity
| Targets | NGF (IC50 ~1 µM); MSI RNA-binding (IC50 = 2.7 μM) |
| ln Vitro |
By attaching to the NGF dimer, Ro 08-2750 most likely causes a change in conformation that prevents NGF from further attaching to p75NTR[2]. Ro 08-2750 (10 nM) completely prevents NGF-induced cell death in SK-N-MC 103 cells[2]. In myeloid leukemia cells, Ro 08-2750 (5-10 μM; 8 hours) increases differentiation and apoptosis[3]. Ro 08-2750 prevents human AML lines and patient cells from surviving[3]. Ro 08-2750 modifies the MSI2 gene signature and inhibits MSI2 RNA-binding[3]. |
| ln Vivo | In a myeloid leukemia model, Ro 08-2750 (13.75 mg/kg; i.p.) inhibits leukemogenesis[3]. |
| References |
[1]. Small-molecule inhibitors of protein-protein interactions: progressing towards the dream. Nat Rev Drug Discov. 2004 Apr;3(4):301-17. [2]. NGF ligand alters NGF signaling via p75(NTR) and trkA. J Neurosci Res. 2000 Aug 1;61(3):263-72. [3]. Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia. Nat Commun. 2019 Jun 19;10(1):2691. |
| Additional Infomation | 7,10-dimethyl-2,4-dioxo-8-benzo[g]pteridinecarboxaldehyde is a flavin. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~4 mg/mL (~14.8 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (18.50 mM) in 50% PEG300 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 5 mg/mL (18.50 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7004 mL | 18.5021 mL | 37.0041 mL | |
| 5 mM | 0.7401 mL | 3.7004 mL | 7.4008 mL | |
| 10 mM | 0.3700 mL | 1.8502 mL | 3.7004 mL |