C25-140 | CAS# 1358099-18-9 | Protein Interaction Inhibitor

MedKoo Cat#: 564689 | Name: C25-140

Description:

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

C25-140 is the first in class protein-protein interaction inhibitor of a RING-E3 ligase (TRAF6) / E2 enzyme (Ubc13) binding.

Chemical Structure

C25-140

CAS#1358099-18-9

Theoretical Analysis

MedKoo Cat#: 564689

Name: C25-140

CAS#: 1358099-18-9

Chemical Formula: C26H31N7O

Exact Mass: 457.2590

Molecular Weight: 457.58

Elemental Analysis: C, 68.25; H, 6.83; N, 21.43; O, 3.50

Price and Availability

Size	Price	Availability
50mg	USD 750.00	2 Weeks
100mg	USD 1,250.00	2 Weeks
200mg	USD 1,950.00	2 Weeks
500mg	USD 3,650.00	2 Weeks
1g	USD 4,650.00	2 Weeks
2g	USD 6,950.00	2 Weeks

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Related CAS #

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Synonym

C25140; C-25140; C 25140; C25 140; C25-140; C-25-140;

IUPAC/Chemical Name

1-(4-Benzylpiperidin-1-yl)-3-(3,5-dimethyl-1-(3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-1H-pyrazol-4-yl)propan-1-one

InChi Key

HFKVRXVHZGBRKF-UHFFFAOYSA-N

InChi Code

InChI=1S/C26H31N7O/c1-18-23(19(2)32(29-18)25-11-10-24-28-27-20(3)33(24)30-25)9-12-26(34)31-15-13-22(14-16-31)17-21-7-5-4-6-8-21/h4-8,10-11,22H,9,12-17H2,1-3H3

SMILES Code

O=C(N1CCC(CC2=CC=CC=C2)CC1)CCC3=C(C)N(C4=NN5C(C=C4)=NN=C5C)N=C3C

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

>3 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

Instruction

View handling instruction

Biological target:

C25-140 is a fairly selective TRAF6-Ubc13 inhibitor, directly binds to TRAF6, and blocks the interaction of TRAF6 with Ubc13.

In vitro activity:

The inhibitory potential of C25-140 was first tested in MEF cells that can be stimulated with pro-inflammatory cytokines IL-1β and TNFα to trigger NF-κB activation. Stimulation of these cells with IL-1β initially induces TRAF6 auto-ubiquitination that is required for signal progression through the IKK complex toward NF-κB activation and expression of NF-κB–dependent target genes. C25-140 treatment of MEF cells led to a dose-dependent reduction of TRAF6 auto-ubiquitination (Fig. 4A) followed by decreased levels of phosphorylated IκBα (Fig. 4B), which translated into diminished target gene expression (Fig. 4C). These data illustrate that inhibition of TRAF6 activity early during IL-1 receptor signaling hampers the signaling cascade toward NF-κB activation. Additionally, TNFα-induced phosphorylation of IκBα (Fig. S4A) as well as NF-κB–induced target gene expression (Fig. S4B) were affected by C25-140 treatment. Taken together, C25-140 efficiently inhibits IL-1β– and TNFα–mediated receptor signaling in the context of cytokine activation. Reference: J Biol Chem. 2018 Aug 24;293(34):13191-13203. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29950522/

In vivo activity:

In a first in vivo mouse model, the effects of C25-140 on psoriasis, an autoimmune disease, were investigated. In this model, psoriasis is induced by imiquimod (IMQ), which activates TLR7 signaling (29), a pathway employing TRAF6 for signal progression. IMQ was topically applied to the shaved back as well as the right ear of mice. On the same regions, C25-140 was topically applied twice daily at a final dose of ∼1.5 mg/kg per application. Parameters describing disease outcome were scored every day, and samples for IL-17 cytokine measurement were collected at day 6 (Fig. 6A). C25-140 was able to significantly reduce the “cumulative score” (Fig. 6B), the overall “thickness score” (Fig. 6C), “scaling” (Fig. 6D), and “erythema” (Fig. 6E). Moreover, analysis of IL-17 cytokine expression in the right ear tissue proved its down-regulation as a consequence of C25-140 treatment (Fig. 6F). This first efficacy study demonstrates that C25-140, an inhibitor of TRAF6 activity, is able to ameliorate symptoms of autoimmune psoriasis. Reference: J Biol Chem. 2018 Aug 24;293(34):13191-13203. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29950522/

	Solvent	mg/mL	mM
Solubility
	DMSO	62.5	136.59

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 457.58 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:

In vitro protocol:

In vivo protocol:

1. Brenke JK, Popowicz GM, Schorpp K, Rothenaigner I, Roesner M, Meininger I, Kalinski C, Ringelstetter L, R'kyek O, Jürjens G, Vincendeau M, Plettenburg O, Sattler M, Krappmann D, Hadian K. Targeting TRAF6 E3 ligase activity with a small-molecule inhibitor combats autoimmunity. J Biol Chem. 2018 Aug 24;293(34):13191-13203. doi: 10.1074/jbc.RA118.002649. Epub 2018 Jun 27. PMID: 29950522; PMCID: PMC6109917. 2. Zeng Q, Ye L, Ling M, Ma R, Li J, Chen H, Pan L. TLR4/TRAF6/NOX2 signaling pathway is involved in ventilation-induced lung injury via endoplasmic reticulum stress in murine model. Int Immunopharmacol. 2021 Jul;96:107774. doi: 10.1016/j.intimp.2021.107774. Epub 2021 May 19. PMID: 34020396.

1: Brenke JK, Popowicz GM, Schorpp K, Rothenaigner I, Roesner M, Meininger I, Kalinski C, Ringelstetter L, R'kyek O, Jürjens G, Vincendeau M, Plettenburg O, Sattler M, Krappmann D, Hadian K. Targeting TRAF6 E3 ligase activity with a small-molecule inhibitor combats autoimmunity. J Biol Chem. 2018 Aug 24;293(34):13191-13203. doi: 10.1074/jbc.RA118.002649. Epub 2018 Jun 27. PubMed PMID: 29950522; PubMed Central PMCID: PMC6109917.