Ro 08-2750 | CAS#37854-59-4 | NGF inhibitior

MedKoo Cat#: 522399 | Name: Ro 08-2750

Description:

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

Ro 08-2750 is a potent and selective Nerve growth factor (NGF) inhibitor that binds the NGF dimer (KD ~ 1 μM). NGF has potential effects on matrix turnover activity and influences the catabolic/anabolic balance of IVD cells in an adverse way that may potentiate IVD degeneration. Anti-NGF treatment might be beneficial to ameliorate progressive tissue breakdown in IVD degeneration and may lead to pain relief.

Chemical Structure

Ro 08-2750

CAS#37854-59-4

Theoretical Analysis

MedKoo Cat#: 522399

Name: Ro 08-2750

CAS#: 37854-59-4

Chemical Formula: C13H10N4O3

Exact Mass: 270.0753

Molecular Weight: 270.25

Elemental Analysis: C, 57.78; H, 3.73; N, 20.73; O, 17.76

Price and Availability

Size	Price	Availability
5mg	USD 110.00	Ready to ship
10mg	USD 180.00	Ready to ship
25mg	USD 385.00	Ready to ship
50mg	USD 655.00	Ready to ship
100mg	USD 1,150.00	Ready to ship
200mg	USD 2,050.00	Ready to ship

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Synonym

Ro 08-2750; Ro08-2750; Ro-08-2750; Ro 082750; Ro -082750; Ro082750.

IUPAC/Chemical Name

2,3,4,10-Tetrahydro-7,10-dimethyl-2,4-dioxobenzo[g]pteridine-8-carboxaldehyde

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)

SMILES Code

O=CC1=C(C)C=C2N=C3C(NC(N=C3N(C)C2=C1)=O)=O

Appearance

Orange to red solid powder

Purity

>95% (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, not in water

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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#BBC51216

View CoA: current batch, Lot#BBC51228

QC Data

View QC data: current batch, Lot#BBC51216

View QC data: current batch, Lot#BBC51228

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Ro 08-2750 is a non-peptide and reversible nerve growth factor (NGF) inhibitor which binds to NGF, and with an IC50 of ~ 1 µM.

In vitro activity:

Ro 08-2750, a small non-peptide molecule, was found to bind to NGF and dimer itself, which induces a concentration-dependent and time-dependent conformational change of NGF that depending on the cell types, cell growth conditions or combination form with receptors. This study found the decreased levels of β-catenin mRNA in the three cells induced by 100 ng/ml NGF can be up-regulated significantly by Ro 08-2750, K252a and LM11A-31. Reference: Oncotarget. 2016 Dec 6; 7(49): 81026–81048. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348374/

In vivo activity:

Using healthy mice, this study also reported no changes in liver enzymes 24 h after Ro treatment (Supplementary Fig. 8g). Although there was no change in leukemia latency in this very aggressive model, disease progression was assessed in both treated and control groups when control mice and treated mice succumbed to disease (day 19 post-transplantation). The treated group exhibited a significant reduction in spleen weights (Fig. 6e), white blood cell counts (Fig. 6f) and c-MYC levels compared with the control group (Fig. 6g). These data support the concept that targeting MSI in vivo could have therapeutic efficacy in AML. Reference: Nat Commun. 2019; 10: 2691. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584500/

	Solvent	mg/mL	mM
Solubility
	DMSO	2.7	10.00

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 270.25 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.

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. Minuesa G, Albanese SK, Xie W, Kazansky Y, Worroll D, Chow A, Schurer A, Park SM, Rotsides CZ, Taggart J, Rizzi A, Naden LN, Chou T, Gourkanti S, Cappel D, Passarelli MC, Fairchild L, Adura C, Glickman JF, Schulman J, Famulare C, Patel M, Eibl JK, Ross GM, Bhattacharya S, Tan DS, Leslie CS, Beuming T, Patel DJ, Goldgur Y, Chodera JD, Kharas MG. Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia. Nat Commun. 2019 Jun 19;10(1):2691. doi: 10.1038/s41467-019-10523-3. PMID: 31217428; PMCID: PMC6584500. 2. Li B, Cai S, Zhao Y, He Q, Yu X, Cheng L, Zhang Y, Hu X, Ke M, Chen S, Zou M. Nerve growth factor modulates the tumor cells migration in ovarian cancer through the WNT/β-catenin pathway. Oncotarget. 2016 Dec 6;7(49):81026-81048. doi: 10.18632/oncotarget.13186. PMID: 27835587; PMCID: PMC5348374.

In vitro protocol:

In vivo protocol:

1: Walters K, Sajek MP, Murphy E, Issaian A, Baldwin A, Harrison E, Daniels M, Reisz JA, Hansen K, D'Alessandro A, Mukherjee N. Small-molecule Ro-08-2750 interacts with many RNA-binding proteins and elicits MUSASHI2-independent phenotypes. RNA. 2023 Oct;29(10):1458-1470. doi: 10.1261/rna.079605.123. Epub 2023 Jun 27. PMID: 37369529; PMCID: PMC10578479. 2: Zhang W, He R, Yang W, Zhang Y, Yuan Q, Wang J, Liu Y, Chen S, Zhang S, Zhang W, Zhu Z, Zhang J, Wang Z, Li J. Autophagic Schwann cells promote perineural invasion mediated by the NGF/ATG7 paracrine pathway in pancreatic cancer. J Exp Clin Cancer Res. 2022 Feb 2;41(1):48. doi: 10.1186/s13046-021-02198-w. PMID: 35109895; PMCID: PMC8809009. 3: Erazo T, Evans CM, Zakheim D, Chu EL, Refermat AY, Asgari Z, Yang X, Da Silva Ferreira M, Mehta S, Russo MV, Knezevic A, Zhang XP, Chen Z, Fennell M, Garippa R, Seshan V, de Stanchina E, Barbash O, Batlevi CL, Leslie CS, Melnick AM, Younes A, Kharas MG. TP53 mutations and RNA-binding protein MUSASHI-2 drive resistance to PRMT5-targeted therapy in B-cell lymphoma. Nat Commun. 2022 Sep 27;13(1):5676. doi: 10.1038/s41467-022-33137-8. PMID: 36167829; PMCID: PMC9515221. 4: Sabater-Arcis M, Bargiela A, Moreno N, Poyatos-Garcia J, Vilchez JJ, Artero R. Musashi-2 contributes to myotonic dystrophy muscle dysfunction by promoting excessive autophagy through miR-7 biogenesis repression. Mol Ther Nucleic Acids. 2021 Aug 19;25:652-667. doi: 10.1016/j.omtn.2021.08.010. PMID: 34589284; PMCID: PMC8463325. 5: Minuesa G, Albanese SK, Xie W, Kazansky Y, Worroll D, Chow A, Schurer A, Park SM, Rotsides CZ, Taggart J, Rizzi A, Naden LN, Chou T, Gourkanti S, Cappel D, Passarelli MC, Fairchild L, Adura C, Glickman JF, Schulman J, Famulare C, Patel M, Eibl JK, Ross GM, Bhattacharya S, Tan DS, Leslie CS, Beuming T, Patel DJ, Goldgur Y, Chodera JD, Kharas MG. Small-molecule targeting of MUSASHI RNA- binding activity in acute myeloid leukemia. Nat Commun. 2019 Jun 19;10(1):2691. doi: 10.1038/s41467-019-10523-3. PMID: 31217428; PMCID: PMC6584500. 6: Wang L, Li J, Wang R, Chen H, Wang R, Wang W, Yang X. NGF Signaling Interacts With the Hippo/YAP Pathway to Regulate Cervical Cancer Progression. Front Oncol. 2021 Oct 14;11:688794. doi: 10.3389/fonc.2021.688794. PMID: 34722240; PMCID: PMC8552705. 7: Lim CT, Tan KW, Wu M, Ulferts R, Armstrong LA, Ozono E, Drury LS, Milligan JC, Zeisner TU, Zeng J, Weissmann F, Canal B, Bineva-Todd G, Howell M, O'Reilly N, Beale R, Kulathu Y, Labib K, Diffley JFX. Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of Nsp3 papain-like protease. Biochem J. 2021 Jul 16;478(13):2517-2531. doi: 10.1042/BCJ20210244. PMID: 34198325; PMCID: PMC8286840. 8: Chakravarthy R, Mnich K, Gorman AM. Nerve growth factor (NGF)-mediated regulation of p75(NTR) expression contributes to chemotherapeutic resistance in triple negative breast cancer cells. Biochem Biophys Res Commun. 2016 Sep 30;478(4):1541-7. doi: 10.1016/j.bbrc.2016.08.149. Epub 2016 Aug 27. PMID: 27577679. 9: Cheng C, Tang S, Cui S, Yang T, Li L, Zhai M, Wei F, Ding G. Nerve growth factor promote osteogenic differentiation of dental pulp stem cells through MEK/ERK signalling pathways. J Cell Mol Med. 2024 Feb;28(4):e18143. doi: 10.1111/jcmm.18143. PMID: 38333908; PMCID: PMC10853700. 10: Sheffield KS, Kennedy AE, Scott JA, Ross GM. Characterizing nerve growth factor-p75(NTR) interactions and small molecule inhibition using surface plasmon resonance spectroscopy. Anal Biochem. 2016 Jan 15;493:21-6. doi: 10.1016/j.ab.2015.09.019. Epub 2015 Oct 3. PMID: 26435172. 11: Gravina GL, Marampon F, Sanità P, Mancini A, Colapietro A, Scarsella L, Jitariuc A, Biordi L, Ficorella C, Festuccia C. Increased expression and activity of p75NTR are crucial events in azacitidine-induced cell death in prostate cancer. Oncol Rep. 2016 Jul;36(1):125-30. doi: 10.3892/or.2016.4832. Epub 2016 May 23. PMID: 27222100. 12: Kao TH, Peng YJ, Salter DM, Lee HS. Nerve growth factor increases MMP9 activity in annulus fibrosus cells by upregulating lipocalin 2 expression. Eur Spine J. 2015 Sep;24(9):1959-68. doi: 10.1007/s00586-014-3675-2. Epub 2014 Nov 21. PMID: 25412834. 13: Eibl JK, Strasser BC, Ross GM. Identification of novel pyrazoloquinazolinecarboxilate analogues to inhibit nerve growth factor in vitro. Eur J Pharmacol. 2013 May 15;708(1-3):30-7. doi: 10.1016/j.ejphar.2013.03.029. Epub 2013 Mar 22. PMID: 23528360. 14: Li B, Cai S, Zhao Y, He Q, Yu X, Cheng L, Zhang Y, Hu X, Ke M, Chen S, Zou M. Nerve growth factor modulates the tumor cells migration in ovarian cancer through the WNT/β-catenin pathway. Oncotarget. 2016 Dec 6;7(49):81026-81048. doi: 10.18632/oncotarget.13186. PMID: 27835587; PMCID: PMC5348374. 15: Sheffield KS, Vohra R, Scott JA, Ross GM. Using surface plasmon resonance spectroscopy to characterize the inhibition of NGF-p75(NTR) and proNGF-p75(NTR) interactions by small molecule inhibitors. Pharmacol Res. 2016 Jan;103:292-9. doi: 10.1016/j.phrs.2015.12.005. Epub 2015 Dec 7. PMID: 26675716. 16: Niederhauser O, Mangold M, Schubenel R, Kusznir EA, Schmidt D, Hertel C. NGF ligand alters NGF signaling via p75(NTR) and trkA. J Neurosci Res. 2000 Aug 1;61(3):263-72. doi: 10.1002/1097-4547(20000801)61:3<263::AID-JNR4>3.0.CO;2-M. PMID: 10900073. 17: Kao TH, Peng YJ, Tsou HK, Salter DM, Lee HS. Nerve growth factor promotes expression of novel genes in intervertebral disc cells that regulate tissue degradation: Laboratory investigation. J Neurosurg Spine. 2014 Oct;21(4):653-61. doi: 10.3171/2014.6.SPINE13756. Epub 2014 Jul 25. PMID: 25062286.