SPD-304 | CAS#869998-49-2 | TNFα inhibitor

MedKoo Cat#: 530541 | Name: SPD-304

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Description:

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

SPD-304 is an inhibitor of tumor necrosis factor α (TNFα). that prevents binding to the TNF Receptor 1 (TNFR1) with an IC50 of 22 µM. Both tumor necrosis factor (TNF)-α and the angiotensin (Ang) II/angiotensin II receptor type 1 (AT1) axis play important roles in neuropathic pain and nociception.

Chemical Structure

SPD-304

CAS#869998-49-2 (free)

Theoretical Analysis

MedKoo Cat#: 530541

Name: SPD-304

CAS#: 869998-49-2 (free)

Chemical Formula: C32H32F3N3O2

Exact Mass: 547.2447

Molecular Weight: 547.62

Elemental Analysis: C, 70.19; H, 5.89; F, 10.41; N, 7.67; O, 5.84

Price and Availability

Size	Price	Availability
5mg	USD 450.00	2 Weeks
10mg	USD 750.00	2 Weeks
25mg	USD 1,250.00	2 Weeks

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Related CAS #

869998-49-2 (free) 1049741-03-8 (HCl)

Synonym

SPD-304, SPD 304, SPD304.

IUPAC/Chemical Name

6,7-dimethyl-3-[[methyl[2-[methyl[[1-[3-(trifluoromethyl)phenyl]-1H-indol-3-yl]methyl]amino]ethyl]amino]methyl]-4H-1-benzopyran-4-one

InChi Key

JZNXLPPJRFFECJ-UHFFFAOYSA-N

InChi Code

InChI=1S/C32H32F3N3O2/c1-21-14-28-30(15-22(21)2)40-20-24(31(28)39)18-37(4)13-12-36(3)17-23-19-38(29-11-6-5-10-27(23)29)26-9-7-8-25(16-26)32(33,34)35/h5-11,14-16,19-20H,12-13,17-18H2,1-4H3

SMILES Code

O=C1C(CN(C)CCN(C)CC2=CN(C3=CC=CC(C(F)(F)F)=C3)C4=C2C=CC=C4)=COC5=CC(C)=C(C)C=C15

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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C21M02C18

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

SPD-304 has an IC50 of 22 µM for inhibiting in vitro TNF receptor 1 (TNFR1) binding to TNF-α.

In vitro activity:

SPD-304 has potential therapeutic uses in neuropathic pain and nociception treatment. in dorsal root ganglion neurons, SPD-304 effectively blocked TNF-α-induced inhibition of angiotensin II receptor type 1 expression at the transcription level. SPD-304 inhibited the activation of p38 MAPK and β-catenin signaling pathways, preventing the increase in soluble β-catenin levels mediated by TNF-α. Reference: Neuroscience. 2013 Sep 17;248:383-91. https://pubmed.ncbi.nlm.nih.gov/23806715/

In vivo activity:

To be determined

	Solvent	mg/mL	mM
Solubility
	DMF	1.0	1.83
	DMSO	10.0	18.26
	Ethanol	1.0	1.83

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 547.62 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. Alexiou P, Papakyriakou A, Ntougkos E, Papaneophytou CP, Liepouri F, Mettou A, Katsoulis I, Maranti A, Tsiliouka K, Strongilos A, Chaitidou S, Douni E, Kontopidis G, Kollias G, Couladouros E, Eliopoulos E. Rationally designed less toxic SPD-304 analogs and preliminary evaluation of their TNF inhibitory effects. Arch Pharm (Weinheim). 2014 Nov;347(11):798-805. doi: 10.1002/ardp.201400198. Epub 2014 Aug 27. PMID: 25160057. 2. Yang Y, Wu H, Yan JQ, Song ZB, Guo QL. Tumor necrosis factor-α inhibits angiotensin II receptor type 1 expression in dorsal root ganglion neurons via β-catenin signaling. Neuroscience. 2013 Sep 17;248:383-91. doi: 10.1016/j.neuroscience.2013.06.018. Epub 2013 Jun 25. PMID: 23806715.

In vitro protocol:

In vivo protocol:

To be determined

1: Sun H, Yost GS. Metabolic activation of a novel 3-substituted indole- containing TNF-alpha inhibitor: dehydrogenation and inactivation of CYP3A4. Chem Res Toxicol. 2008 Feb;21(2):374-85. doi: 10.1021/tx700294g. Epub 2007 Dec 21. PMID: 18095656. 2: Papaneophytou CP, Rinotas V, Douni E, Kontopidis G. A statistical approach for optimization of RANKL overexpression in Escherichia coli: purification and characterization of the protein. Protein Expr Purif. 2013 Jul;90(1):9-19. doi: 10.1016/j.pep.2013.04.005. Epub 2013 Apr 25. PMID: 23623854. 3: Yang Y, Wu H, Yan JQ, Song ZB, Guo QL. Tumor necrosis factor-α inhibits angiotensin II receptor type 1 expression in dorsal root ganglion neurons via β-catenin signaling. Neuroscience. 2013 Sep 17;248:383-91. doi: 10.1016/j.neuroscience.2013.06.018. Epub 2013 Jun 25. PMID: 23806715. 4: Alexiou P, Papakyriakou A, Ntougkos E, Papaneophytou CP, Liepouri F, Mettou A, Katsoulis I, Maranti A, Tsiliouka K, Strongilos A, Chaitidou S, Douni E, Kontopidis G, Kollias G, Couladouros E, Eliopoulos E. Rationally designed less toxic SPD-304 analogs and preliminary evaluation of their TNF inhibitory effects. Arch Pharm (Weinheim). 2014 Nov;347(11):798-805. doi: 10.1002/ardp.201400198. Epub 2014 Aug 27. PMID: 25160057. 5: Chang YJ, Hsu SL, Liu YT, Lin YH, Lin MH, Huang SJ, Ho JA, Wu LC. Gallic acid induces necroptosis via TNF-α signaling pathway in activated hepatic stellate cells. PLoS One. 2015 Mar 27;10(3):e0120713. doi: 10.1371/journal.pone.0120713. PMID: 25816210; PMCID: PMC4376672. 6: Blevitt JM, Hack MD, Herman KL, Jackson PF, Krawczuk PJ, Lebsack AD, Liu AX, Mirzadegan T, Nelen MI, Patrick AN, Steinbacher S, Milla ME, Lumb KJ. Structural Basis of Small-Molecule Aggregate Induced Inhibition of a Protein-Protein Interaction. J Med Chem. 2017 Apr 27;60(8):3511-3517. doi: 10.1021/acs.jmedchem.6b01836. Epub 2017 Mar 16. PMID: 28300404. 7: Kanada R, Tanabe M, Muromoto R, Sato Y, Kuwahara T, Fukuda H, Arisawa M, Matsuda T, Watanabe M, Shuto S. Synthesis of Chiral cis-Cyclopropane Bearing Indole and Chromone as Potential TNFα Inhibitors. J Org Chem. 2018 Aug 3;83(15):7672-7682. doi: 10.1021/acs.joc.8b00466. Epub 2018 Jul 24. PMID: 30004223. 8: Sun W, Wu Y, Zheng M, Yang Y, Liu Y, Wu C, Zhou Y, Zhang Y, Chen L, Li H. Discovery of an Orally Active Small-Molecule Tumor Necrosis Factor-α Inhibitor. J Med Chem. 2020 Aug 13;63(15):8146-8156. doi: 10.1021/acs.jmedchem.0c00377. Epub 2020 Jul 30. PMID: 32667202. 9: Rinotas V, Papakyriakou A, Violitzi F, Papaneophytou C, Ouzouni MD, Alexiou P, Strongilos A, Couladouros E, Kontopidis G, Eliopoulos E, Douni E. Discovery of Small-Molecule Inhibitors of Receptor Activator of Nuclear Factor-κB Ligand with a Superior Therapeutic Index. J Med Chem. 2020 Oct 22;63(20):12043-12059. doi: 10.1021/acs.jmedchem.0c01316. Epub 2020 Oct 2. PMID: 32955874. 10: Khalid M, Alqarni MH, Shoaib A, Arif M, Foudah AI, Afzal O, Ali A, Ali A, Alqahtani SS, Altamimi ASA. Anti-Arthritic and Anti-Inflammatory Potential of Spondias mangifera Extract Fractions: An In Silico, In Vitro and In Vivo Approach. Plants (Basel). 2021 Apr 21;10(5):825. doi: 10.3390/plants10050825. PMID: 33919084; PMCID: PMC8143105.