IKK-16 free base | CAS#873225-46-8 | 1186195-62-9 | IκB kinase inhibitor

MedKoo Cat#: 407163 | Name: IKK-16 (free base)

Description:

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

IKK-16 is a potent and slective inhibitor of IκB kinase (IKK) (IC50 values are 40, 70 and 200 nM for IKKβ, IKK complex and IKKα respectively). KK-16 inhibits TNFα-stimulated expression of the adhesion molecules E-selectin, ICAM-1, and VCAM-1 in HUVEC cells.

Chemical Structure

IKK-16 (free base)

CAS#873225-46-8 (free base)

Theoretical Analysis

MedKoo Cat#: 407163

Name: IKK-16 (free base)

CAS#: 873225-46-8 (free base)

Chemical Formula: C28H29N5OS

Exact Mass: 483.2093

Molecular Weight: 483.63

Elemental Analysis: C, 69.54; H, 6.04; N, 14.48; O, 3.31; S, 6.63

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship
500mg	USD 2,850.00	Ready to ship

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Related CAS #

873225-46-8 (free base) 1186195-62-9 (HCl)

Synonym

IKK-16; IKK 16; IKK16; IKK-16

IUPAC/Chemical Name

(4-((4-(benzo[b]thiophen-2-yl)pyrimidin-2-yl)amino)phenyl)(4-(pyrrolidin-1-yl)piperidin-1-yl)methanone

InChi Key

BWZJBXAPRCVCKQ-UHFFFAOYSA-N

InChi Code

InChI=1S/C28H29N5OS/c34-27(33-17-12-23(13-18-33)32-15-3-4-16-32)20-7-9-22(10-8-20)30-28-29-14-11-24(31-28)26-19-21-5-1-2-6-25(21)35-26/h1-2,5-11,14,19,23H,3-4,12-13,15-18H2,(H,29,30,31)

SMILES Code

O=C(C1=CC=C(NC2=NC=CC(C3=CC4=CC=CC=C4S3)=N2)C=C1)N5CCC(N6CCCC6)CC5

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, 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

Related CAS# 873225-46-8 ( IKK-16 free base) 1186195-62-9 ( IKK-16 HCl salt).

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#BBC60111

QC Data

View QC data: current batch, Lot#BBC60111

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

IKK 16 is a selective IκB kinase (IKK) inhibitor for the IKK2, IKK complex and IKK1 with IC50s of 40 nM, 70 nM and 200 nM, respectively. IKK16 also inhibits leucine-rich repeat kinase-2 (LRRK2) with an IC50 of 50 nM.

In vitro activity:

The treatment of SKBR3 cells with rising concentrations of IKK-16 resulted in a highly significant decrease in cell viability (5 μM p < 0.0001; 50 μM p < 0.0001). In contrast, applying IKK-16 to HaCat cells led to a slight but significant increase in cell viability for the application of 5 μM (p < 0.05). Increasing the concentration resulted in a highly significant decrease in cell viability (p < 0.0001; Figure 1). The application of 50 μM IKK-16 to the SKBR3 cell line severely diminished the seeded cell population leaving only cell debris. All applied concentrations of IKK-16 significantly reduced the RelA/PTPIP51 interaction (0.5 μM p < 0.01; 5 μM p < 0.05) in the breast cancer cell line SKBR3. On the contrary, the application of IKK-16 to HaCat cells enhanced the interaction of RelA and PTPIP51 for the highest tested concentration (50 μM p < 0.05). Reference: Future Sci OA. 2020 Mar 4;6(5):FSO463. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/32518680/

In vivo activity:

IKK-16 (compound 16) was also tested in two animal models. First, its efficacy to inhibit TNFα release into plasma upon LPS-challenge in the rat was determined. The compound was dosed sc (30 mg/kg) or orally (30 mg/kg) 1 h prior to the LPS-challenge. Four hours after the challenge, plasma was collected and the systemic TNFα levels were analyzed using a commercially available ELISA kit. Both routes of administration of inhibitor 16 at the indicated dose resulted in a significant inhibition of 86% (sc) and 75% (p.o.).12 In a second experiment, it was shown that compound 16 was also active in the thioglycollate-induced peritonitis model in the mouse. The maximal inhibition of neutrophil extravasation in this model was about 50% at a dose of 10 mg/kg sc. Reference: Bioorg Med Chem Lett. 2006 Jan 1;16(1):108-12. https://linkinghub.elsevier.com/retrieve/pii/S0960-894X(05)01203-5

	Solvent	mg/mL	mM
Solubility
	DMSO	27.0	55.83

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 483.63 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:

1. Dietel E, Brobeil A, Tag C, Gattenloehner S, Wimmer M. PTPIP51 crosslinks the NFκB signaling and the MAPK pathway in SKBR3 cells. Future Sci OA. 2020 Mar 4;6(5):FSO463. doi: 10.2144/fsoa-2019-0136. PMID: 32518680; PMCID: PMC7273389. 2. Waelchli R, Bollbuck B, Bruns C, Buhl T, Eder J, Feifel R, Hersperger R, Janser P, Revesz L, Zerwes HG, Schlapbach A. Design and preparation of 2-benzamido-pyrimidines as inhibitors of IKK. Bioorg Med Chem Lett. 2006 Jan 1;16(1):108-12. doi: 10.1016/j.bmcl.2005.09.035. Epub 2005 Oct 19. PMID: 16236504.

In vivo protocol:

1. Waelchli R, Bollbuck B, Bruns C, Buhl T, Eder J, Feifel R, Hersperger R, Janser P, Revesz L, Zerwes HG, Schlapbach A. Design and preparation of 2-benzamido-pyrimidines as inhibitors of IKK. Bioorg Med Chem Lett. 2006 Jan 1;16(1):108-12. doi: 10.1016/j.bmcl.2005.09.035. Epub 2005 Oct 19. PMID: 16236504.

1: Tandon M, Johnson J, Li Z, Xu S, Wipf P, Wang QJ. New pyrazolopyrimidine inhibitors of protein kinase d as potent anticancer agents for prostate cancer cells. PLoS One. 2013 Sep 23;8(9):e75601. doi: 10.1371/journal.pone.0075601. PubMed PMID: 24086585; PubMed Central PMCID: PMC3781056. 2: Mehmood T, Maryam A, Zhang H, Li Y, Khan M, Ma T. Deoxyelephantopin induces apoptosis in HepG2 cells via oxidative stress, NF-κB inhibition and mitochondrial dysfunction. Biofactors. 2016 Sep 15. doi: 10.1002/biof.1324. [Epub ahead of print] PubMed PMID: 27628030. 3: Shu YS, Tao W, Miao QB, Zhu YB, Yang YF. Improvement of ventilation-induced lung injury in a rodent model by inhibition of inhibitory κB kinase. J Trauma Acute Care Surg. 2014 Jun;76(6):1417-24. doi: 10.1097/TA.0000000000000229. PubMed PMID: 24854310. 4: Coldewey SM, Rogazzo M, Collino M, Patel NS, Thiemermann C. Inhibition of IκB kinase reduces the multiple organ dysfunction caused by sepsis in the mouse. Dis Model Mech. 2013 Jul;6(4):1031-42. doi: 10.1242/dmm.012435. PubMed PMID: 23649820; PubMed Central PMCID: PMC3701222. 5: Ansbro MR, Shukla S, Ambudkar SV, Yuspa SH, Li L. Screening compounds with a novel high-throughput ABCB1-mediated efflux assay identifies drugs with known therapeutic targets at risk for multidrug resistance interference. PLoS One. 2013 Apr 10;8(4):e60334. doi: 10.1371/journal.pone.0060334. PubMed PMID: 23593196; PubMed Central PMCID: PMC3622673. 6: Chen J, Kieswich JE, Chiazza F, Moyes AJ, Gobbetti T, Purvis GS, Salvatori DC, Patel NS, Perretti M, Hobbs AJ, Collino M, Yaqoob MM, Thiemermann C. IκB Kinase Inhibitor Attenuates Sepsis-Induced Cardiac Dysfunction in CKD. J Am Soc Nephrol. 2016 May 6. pii: ASN.2015060670. [Epub ahead of print] PubMed PMID: 27153924. 7: Shu Y, Liu Y, Li X, Cao L, Yuan X, Li W, Cao Q. Aspirin-Triggered Resolvin D1 Inhibits TGF-β1-Induced EndMT through Increasing the Expression of Smad7 and Is Closely Related to Oxidative Stress. Biomol Ther (Seoul). 2016 Mar 1;24(2):132-9. doi: 10.4062/biomolther.2015.088. PubMed PMID: 26869523; PubMed Central PMCID: PMC4774493. 8: Dobritsa SV, Kuok IT, Nguyen H, Webster JC, Spragg AM, Morley T, Carr GJ. Development of a high-throughput cell-based assay for identification of IL-17 inhibitors. J Biomol Screen. 2013 Jan;18(1):75-84. doi: 10.1177/1087057112459350. PubMed PMID: 22983163.