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MedKoo Cat#: 574616 | Name: CC-401 free base
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Description:

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

CC-401, also known as JNK-401, is a potent, selective, ATP-competitive pan-JNK inhibitor that decreases hepatic necrosis and apoptosis, significantly reduces tubular apoptosis in the obstructed kidney, sensitizes hypoxic colon cancer cells to DNA-damaging agents, and potentiates the effect of bevacizumab and oxaliplatin in HT29-derived mouse xenografts. CC-401 Promotes β-Cell Replication via Pleiotropic Consequences of DYRK1A/B Inhibition.

Chemical Structure

CC-401 free base
CC-401 free base
CAS#395104-30-0 (free base)

Theoretical Analysis

MedKoo Cat#: 574616

Name: CC-401 free base

CAS#: 395104-30-0 (free base)

Chemical Formula: C22H24N6O

Exact Mass: 388.2012

Molecular Weight: 388.47

Elemental Analysis: C, 68.02; H, 6.23; N, 21.63; O, 4.12

Price and Availability

Size Price Availability Quantity
5mg USD 350.00 2 Weeks
25mg USD 950.00 2 Weeks
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Related CAS #
395104-30-0 (free base) 1438391-30-0 (HCl)
Synonym
CC-401, CC401, CC 401; JNK-401; JNK401; JNK 401
IUPAC/Chemical Name
3-[3-[2-(1-piperidinyl)ethoxy]phenyl]-5-(1H-1,2,4-triazol-5-yl)-1H-indazole
InChi Key
XDJCLCLBSGGNKS-UHFFFAOYSA-N
InChi Code
InChI=1S/C22H24N6O/c1-2-9-28(10-3-1)11-12-29-18-6-4-5-16(13-18)21-19-14-17(22-23-15-24-27-22)7-8-20(19)25-26-21/h4-8,13-15H,1-3,9-12H2,(H,25,26)(H,23,24,27)
SMILES Code
C1(C2=CC=CC(OCCN3CCCCC3)=C2)=NNC4=C1C=C(C5=NC=NN5)C=C4
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:
CC-401 is a potent inhibitor of all three forms of JNK with Ki of 25 to 50 nM.
In vitro activity:
To investigate whether JNK blockade directly inhibits TGF-β1 production, the effect of CC-401 on AngII–induced TGF-β1 secretion was examined by the proximal tubular epithelial cell line HK-2. The addition of 1 μM AngII induced a two-fold increase in TGF-β1 secretion, which was suppressed in a dosage-dependent manner by CC-401, with a significant reduction observed with 4 μM CC-401 (Figure 10). Tubular epithelial cell apoptosis was evident in the obstructed kidney as assessed by immunostaining for cleaved caspase-3, and this was reduced by approximately 50% with CC-401 treatment (Figure 11A). Apoptosis of interstitial cells also was evident in the obstructed kidney. This was reduced by CC-401 treatment, but this failed to reach statistical significance (Figure 11B). A marked increase in the proliferation of interstitial and tubular cells was apparent in the obstructed kidney (Figure 11, C and D). Although CC-401 reduced the mean number of BrdU+ proliferating interstitial cells, this did not reach statistical significance. Last, interstitial accumulation of ED1+ macrophages in the obstructed kidney was not affected by CC-401 treatment (Figure 11E). Reference: J Am Soc Nephrol. 2007 Feb;18(2):472-84. https://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=17202416
In vivo activity:
Animals were treated with the JNK inhibitor, CC-401, vehicle alone, or no treatment from day 7 until being killed on day 24 of disease. Untreated animals at day 7 showed significant proteinuria, focal glomerular lesions, marked glomerular macrophage and T-cell accumulation, and upregulation of proinflammatory mediators (TNF-alpha, iNOS, MMP-12). Untreated and vehicle-treated groups displayed severe glomerulonephritis at day 24 with renal impairment and worsening proteinuria. These animals had severe glomerular lesions, with 60% of glomeruli exhibiting fibrocellular crescents, in association with increased macrophage and T-cell accumulation (including macrophage giant cells) and a further increase in mRNA levels of TNF-alpha, iNOS, MMP-12, and TGF-beta1. In contrast, CC-401 treatment prevented renal impairment, suppressed proteinuria, and prevented severe glomerular and tubulointerstitial lesions, including crescent formation and granulomatous-like lesions. These protective effects were independent of glomerular macrophage and T-cell accumulation, and of the humoral immune response. CC-401 treatment inhibited expression of both pro- and antiinflammatory molecules (interleukin-10 and heme oxygenase-1). Reference: Lab Invest. 2009 Apr;89(4):470-84. https://doi.org/10.1038/labinvest.2009.2

Preparing Stock Solutions

The following data is based on the product molecular weight 388.47 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.

Recalculate based on batch purity %
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. Ma FY, Flanc RS, Tesch GH, Han Y, Atkins RC, Bennett BL, Friedman GC, Fan JH, Nikolic-Paterson DJ. A pathogenic role for c-Jun amino-terminal kinase signaling in renal fibrosis and tubular cell apoptosis. J Am Soc Nephrol. 2007 Feb;18(2):472-84. doi: 10.1681/ASN.2006060604. Epub 2007 Jan 3. PMID: 17202416.
In vivo protocol:
1. Ma FY, Flanc RS, Tesch GH, Bennett BL, Friedman GC, Nikolic-Paterson DJ. Blockade of the c-Jun amino terminal kinase prevents crescent formation and halts established anti-GBM glomerulonephritis in the rat. Lab Invest. 2009 Apr;89(4):470-84. doi: 10.1038/labinvest.2009.2. Epub 2009 Feb 2. PMID: 19188913.
1: Abdolazimi Y, Zhao Z, Lee S, Xu H, Allegretti P, Horton TM, Yeh B, Moeller HP, Nichols RJ, McCutcheon D, Shalizi A, Smith M, Armstrong NA, Annes JP. CC-401 Promotes β-Cell Replication via Pleiotropic Consequences of DYRK1A/B Inhibition. Endocrinology. 2018 Sep 1;159(9):3143-3157. doi: 10.1210/en.2018-00083. PMID: 29514186; PMCID: PMC6287593. 2: Zhang H, Niu X, Qian Z, Qian J, Xuan B. The c-Jun N-terminal kinase inhibitor SP600125 inhibits human cytomegalovirus replication. J Med Virol. 2015 Dec;87(12):2135-44. doi: 10.1002/jmv.24286. Epub 2015 Jun 16. PMID: 26058558. 3: Vasilevskaya IA, Selvakumaran M, Hierro LC, Goldstein SR, Winkler JD, O'Dwyer PJ. Inhibition of JNK Sensitizes Hypoxic Colon Cancer Cells to DNA-Damaging Agents. Clin Cancer Res. 2015 Sep 15;21(18):4143-52. doi: 10.1158/1078-0432.CCR-15-0352. Epub 2015 May 28. PMID: 26023085; PMCID: PMC4573818. 4: Gan LT, Van Rooyen DM, Koina ME, McCuskey RS, Teoh NC, Farrell GC. Hepatocyte free cholesterol lipotoxicity results from JNK1-mediated mitochondrial injury and is HMGB1 and TLR4-dependent. J Hepatol. 2014 Dec;61(6):1376-84. doi: 10.1016/j.jhep.2014.07.024. Epub 2014 Jul 24. PMID: 25064435. 5: Kanellis J, Ma FY, Kandane-Rathnayake R, Dowling JP, Polkinghorne KR, Bennett BL, Friedman GC, Nikolic-Paterson DJ. JNK signalling in human and experimental renal ischaemia/reperfusion injury. Nephrol Dial Transplant. 2010 Sep;25(9):2898-908. doi: 10.1093/ndt/gfq147. Epub 2010 Apr 5. PMID: 20368303. 6: Ma FY, Flanc RS, Tesch GH, Bennett BL, Friedman GC, Nikolic-Paterson DJ. Blockade of the c-Jun amino terminal kinase prevents crescent formation and halts established anti-GBM glomerulonephritis in the rat. Lab Invest. 2009 Apr;89(4):470-84. doi: 10.1038/labinvest.2009.2. Epub 2009 Feb 2. PMID: 19188913. 7: Han SY. c-Jun N-Terminal Kinase Signaling Inhibitors Under Development. Toxicol Res. 2008 Jun;24(2):93-100. doi: 10.5487/TR.2008.24.2.093. Epub 2008 Jun 1. PMID: 32038782; PMCID: PMC7006258. 8: Flanc RS, Ma FY, Tesch GH, Han Y, Atkins RC, Bennett BL, Friedman GC, Fan JH, Nikolic-Paterson DJ. A pathogenic role for JNK signaling in experimental anti- GBM glomerulonephritis. Kidney Int. 2007 Sep;72(6):698-708. doi: 10.1038/sj.ki.5002404. Epub 2007 Jun 27. PMID: 17597698. 9: Ma FY, Flanc RS, Tesch GH, Han Y, Atkins RC, Bennett BL, Friedman GC, Fan JH, Nikolic-Paterson DJ. A pathogenic role for c-Jun amino-terminal kinase signaling in renal fibrosis and tubular cell apoptosis. J Am Soc Nephrol. 2007 Feb;18(2):472-84. doi: 10.1681/ASN.2006060604. Epub 2007 Jan 3. PMID: 17202416. 10: Uehara T, Bennett B, Sakata ST, Satoh Y, Bilter GK, Westwick JK, Brenner DA. JNK mediates hepatic ischemia reperfusion injury. J Hepatol. 2005 Jun;42(6):850-9. doi: 10.1016/j.jhep.2005.01.030. Epub 2005 Apr 7. PMID: 15885356. 11: Uehara T, Xi Peng X, Bennett B, Satoh Y, Friedman G, Currin R, Brenner DA, Lemasters J. c-Jun N-terminal kinase mediates hepatic injury after rat liver transplantation. Transplantation. 2004 Aug 15;78(3):324-32. doi: 10.1097/01.tp.0000128859.42696.28. PMID: 15316358.