KCC009

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

MedKoo CAT#: 407381

CAS#: 744198-19-4

Description: KCC009 is a potent and selective Transglutaminase 2 Inhibitor. KCC009 exhibits potent radiosensitization effects in human lung cancer cells expressing wild-type or mutant p53 with different mechanisms. KCC009 disrupts fibronectin assembly in the extracellular matrix and sensitizes orthotopic glioblastomas to chemotherapy. KCC009 decreased DDC-induced liver enlargement without affecting MB formation or extent of liver injury. KCC-009 significantly attenuated the damaging effects of warfarin on arterial tissue.


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KCC009 is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 407381
Name: KCC009
CAS#: 744198-19-4
Chemical Formula: C21H22BrN3O5
Exact Mass: 475.0743
Molecular Weight: 476.327
Elemental Analysis: C, 52.95; H, 4.66; Br, 16.78; N, 8.82; O, 16.79


Related CAS #: 120244-89-5 (S-isomer of KCC009)   744198-19-4 (KCC009)  

Synonym: KCC009; KCC-009; KCC 009.

IUPAC/Chemical Name: benzyl ((2S)-1-(((3-bromo-4,5-dihydroisoxazol-5-yl)methyl)amino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)carbamate

InChi Key: MRULUIQNANUWTK-ZVAWYAOSSA-N

InChi Code: InChI=1S/C21H22BrN3O5/c22-19-11-17(30-25-19)12-23-20(27)18(10-14-6-8-16(26)9-7-14)24-21(28)29-13-15-4-2-1-3-5-15/h1-9,17-18,26H,10-13H2,(H,23,27)(H,24,28)/t17?,18-/m0/s1

SMILES Code: O=C(OCC1=CC=CC=C1)N[C@@H](CC2=CC=C(O)C=C2)C(NCC3CC(Br)=NO3)=O


Technical Data

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).

Harmonized System Code:
293490


Additional Information

KCC009 S-isomer has CAS#120244-89-5 also called ERW 1095A, or RS 10823


References

1: Huaying S, Dong Y, Chihong Z, Xiaoqian Q, Danying W, Jianguo F. Transglutaminase 2 Inhibitor KCC009 Induces p53-Independent Radiosensitization in Lung Adenocarcinoma Cells. Med Sci Monit. 2016 Dec 21;22:5041-5048. PubMed PMID: 28002389; PubMed Central PMCID: PMC5198751.

2: Yuan L, Siegel M, Choi K, Khosla C, Miller CR, Jackson EN, Piwnica-Worms D, Rich KM. Transglutaminase 2 inhibitor, KCC009, disrupts fibronectin assembly in the extracellular matrix and sensitizes orthotopic glioblastomas to chemotherapy. Oncogene. 2007 Apr 19;26(18):2563-73. PubMed PMID: 17099729.

3: Strnad P, Siegel M, Toivola DM, Choi K, Kosek JC, Khosla C, Omary MB. Pharmacologic transglutaminase inhibition attenuates drug-primed liver hypertrophy but not Mallory body formation. FEBS Lett. 2006 Apr 17;580(9):2351--2357. PubMed PMID: 16616523.

4: Konoplyannikov M, Nurminskaya M. New therapeutic approaches to arterial calcification via inhibition of transglutaminase and β-catenin signaling. Curr Pharm Des. 2014;20(37):5811-20. Review. PubMed PMID: 24533936.

5: Beazley KE, Banyard D, Lima F, Deasey SC, Nurminsky DI, Konoplyannikov M, Nurminskaya MV. Transglutaminase inhibitors attenuate vascular calcification in a preclinical model. Arterioscler Thromb Vasc Biol. 2013 Jan;33(1):43-51. doi: 10.1161/ATVBAHA.112.300260. PubMed PMID: 23117658; PubMed Central PMCID: PMC3544469.

6: Frese-Schaper M, Schardt JA, Sakai T, Carboni GL, Schmid RA, Frese S. Inhibition of tissue transglutaminase sensitizes TRAIL-resistant lung cancer cells through upregulation of death receptor 5. FEBS Lett. 2010 Jul 2;584(13):2867-71. doi: 10.1016/j.febslet.2010.04.072. PubMed PMID: 20450916.

7: Yuan L, Behdad A, Siegel M, Khosla C, Higashikubo R, Rich KM. Tissue transgluaminase 2 expression in meningiomas. J Neurooncol. 2008 Nov;90(2):125-32. doi: 10.1007/s11060-008-9642-1. PubMed PMID: 18587533; PubMed Central PMCID: PMC3732188.

8: Cao L, Petrusca DN, Satpathy M, Nakshatri H, Petrache I, Matei D. Tissue transglutaminase protects epithelial ovarian cancer cells from cisplatin-induced apoptosis by promoting cell survival signaling. Carcinogenesis. 2008 Oct;29(10):1893-900. doi: 10.1093/carcin/bgn158. PubMed PMID: 18667446; PubMed Central PMCID: PMC2556973.

9: Yuan L, Holmes TC, Watts RE, Khosla C, Broekelmann TJ, Mecham R, Zheng H, Izaguirre EW, Rich KM. Novel chemo-sensitizing agent, ERW1227B, impairs cellular motility and enhances cell death in glioblastomas. J Neurooncol. 2011 Jun;103(2):207-19. doi: 10.1007/s11060-010-0379-2. PubMed PMID: 20824305; PubMed Central PMCID: PMC3732656.

10: Deasey S, Grichenko O, Du S, Nurminskaya M. Characterization of the transglutaminase gene family in zebrafish and in vivo analysis of transglutaminase-dependent bone mineralization. Amino Acids. 2012 Feb;42(2-3):1065-75. doi: 10.1007/s00726-011-1021-0. PubMed PMID: 21809079; PubMed Central PMCID: PMC3266987.

11: Deasey S, Shanmugasundaram S, Nurminskaya M. Tissue-specific responses to loss of transglutaminase 2. Amino Acids. 2013 Jan;44(1):179-87. doi: 10.1007/s00726-011-1183-9. PubMed PMID: 22194042; PubMed Central PMCID: PMC3536932.

12: Verhaar R, Jongenelen CA, Gerard M, Baekelandt V, Van Dam AM, Wilhelmus MM, Drukarch B. Blockade of enzyme activity inhibits tissue transglutaminase-mediated transamidation of α-synuclein in a cellular model of Parkinson's disease. Neurochem Int. 2011 Jun;58(7):785-93. doi: 10.1016/j.neuint.2011.03.004. PubMed PMID: 21440023.

13: van Strien ME, de Vries HE, Chrobok NL, Bol JG, Breve JJ, van der Pol SM, Kooij G, van Buul JD, Karpuj M, Steinman L, Wilhelmus MM, Sestito C, Drukarch B, Van Dam AM. Tissue Transglutaminase contributes to experimental multiple sclerosis pathogenesis and clinical outcome by promoting macrophage migration. Brain Behav Immun. 2015 Nov;50:141-54. doi: 10.1016/j.bbi.2015.06.023. PubMed PMID: 26133787.

14: Matic I, Sacchi A, Rinaldi A, Melino G, Khosla C, Falasca L, Piacentini M. Characterization of transglutaminase type II role in dendritic cell differentiation and function. J Leukoc Biol. 2010 Jul;88(1):181-8. doi: 10.1189/jlb.1009691. PubMed PMID: 20371597; PubMed Central PMCID: PMC3210574.

15: Lee JH, Jeong J, Jeong EM, Cho SY, Kang JW, Lim J, Heo J, Kang H, Kim IG, Shin DM. Endoplasmic reticulum stress activates transglutaminase 2 leading to protein aggregation. Int J Mol Med. 2014 Apr;33(4):849-55. doi: 10.3892/ijmm.2014.1640. PubMed PMID: 24481335; PubMed Central PMCID: PMC3976127.

16: Satpathy M, Shao M, Emerson R, Donner DB, Matei D. Tissue transglutaminase regulates matrix metalloproteinase-2 in ovarian cancer by modulating cAMP-response element-binding protein activity. J Biol Chem. 2009 Jun 5;284(23):15390-9. doi: 10.1074/jbc.M808331200. PubMed PMID: 19324884; PubMed Central PMCID: PMC2708835.

17: Yuan L, Choi K, Khosla C, Zheng X, Higashikubo R, Chicoine MR, Rich KM. Tissue transglutaminase 2 inhibition promotes cell death and chemosensitivity in glioblastomas. Mol Cancer Ther. 2005 Sep;4(9):1293-302. PubMed PMID: 16170020.