WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 558221
Description: KNK437 is a novel inhibitor of acquisition of thermotolerance and heat shock protein. KNK437 inhibit stress-induced synthesis of heat shock proteins (HSPs). KNK437 is an effective radiosensitizer that targets multiple pro-survival stress response pathways. KNK437 is a useful agent for enhancing the efficiency of hyperthermic therapy which has less toxic side-effects in prostate cancer.
MedKoo Cat#: 558221
Chemical Formula: C13H11NO4
Exact Mass: 245.06881
Molecular Weight: 245.23
Elemental Analysis: C, 63.67; H, 4.52; N, 5.71; O, 26.10
Synonym: KNK437; KNK-437; KNK 437.
IUPAC/Chemical Name: (Z)-3-(benzo[d][1,3]dioxol-5-ylmethylene)-2-oxopyrrolidine-1-carbaldehyde
InChi Key: NJBBLOIWMSYVCQ-VZTVMPNDSA-N
InChi Code: InChI=1S/C33H41N5O6S2/c1-33(2,3)37-31(42)26-19-46-20-38(26)32(43)29(40)24(15-21-9-6-5-7-10-21)36-30(41)25(18-45-4)35-28(39)17-44-27-12-8-11-22-16-34-14-13-23(22)27/h5-14,16,24-26,29,40H,15,17-20H2,1-4H3,(H,35,39)(H,36,41)(H,37,42)/t24-,25-,26-,29-/m0/s1
SMILES Code: O=CN1C(/C(CC1)=C\C2=CC=C(OCO3)C3=C2)=O
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
The following data is based on the product molecular weight 245.23 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|
1: Oommen D, Prise KM. KNK437, abrogates hypoxia-induced radioresistance by dual targeting of the AKT and HIF-1α survival pathways. Biochem Biophys Res Commun. 2012 May 11;421(3):538-43. doi: 10.1016/j.bbrc.2012.04.040. Epub 2012 Apr 13. PubMed PMID: 22521642.
2: Sahin E, Sahin M, Sanlioğlu AD, Gümüslü S. KNK437, a benzylidene lactam compound, sensitises prostate cancer cells to the apoptotic effect of hyperthermia. Int J Hyperthermia. 2011;27(1):63-73. doi: 10.3109/02656736.2010.528139. Epub 2011 Jan 4. PubMed PMID: 21204621.
3: Taba K, Kuramitsu Y, Ryozawa S, Yoshida K, Tanaka T, Mori-Iwamoto S, Maehara S, Maehara Y, Sakaida I, Nakamura K. KNK437 downregulates heat shock protein 27 of pancreatic cancer cells and enhances the cytotoxic effect of gemcitabine. Chemotherapy. 2011;57(1):12-6. doi: 10.1159/000321019. Epub 2010 Dec 3. PubMed PMID: 21124027.
4: Inoue H, Uyama T, Hayashi J, Watanabe A, Kobayashi K, Tadokoro T, Yamamoto Y. N-Formyl-3,4-methylenedioxy-benzylidene-gamma-butyrolaetam, KNK437 induces caspase-3 activation through inhibition of mTORC1 activity in Cos-1 cells. Biochem Biophys Res Commun. 2010 Apr 23;395(1):56-60. doi: 10.1016/j.bbrc.2010.03.134. Epub 2010 Mar 27. PubMed PMID: 20350529.
5: Wu YC, Yen WY, Lee TC, Yih LH. Heat shock protein inhibitors, 17-DMAG and KNK437, enhance arsenic trioxide-induced mitotic apoptosis. Toxicol Appl Pharmacol. 2009 Apr 15;236(2):231-8. doi: 10.1016/j.taap.2009.02.003. Epub 2009 Feb 12. PubMed PMID: 19371599.
6: Voyer J, Heikkila JJ. Comparison of the effect of heat shock factor inhibitor, KNK437, on heat shock- and chemical stress-induced hsp30 gene expression in Xenopus laevis A6 cells. Comp Biochem Physiol A Mol Integr Physiol. 2008 Oct;151(2):253-61. doi: 10.1016/j.cbpa.2008.07.004. Epub 2008 Jul 10. PubMed PMID: 18675372.
7: Manwell LA, Heikkila JJ. Examination of KNK437- and quercetin-mediated inhibition of heat shock-induced heat shock protein gene expression in Xenopus laevis cultured cells. Comp Biochem Physiol A Mol Integr Physiol. 2007 Nov;148(3):521-30. Epub 2007 Jul 5. PubMed PMID: 17681842.
8: Matsuda K, Nakagawa SY, Nakano T, Asaumi J, Jagetia GC, Kawasaki S. Effects of KNK437 on heat-induced methylation of histone H3 in human oral squamous cell carcinoma cells. Int J Hyperthermia. 2006 Dec;22(8):729-35. PubMed PMID: 17391001.
9: Koike T, Uno S, Ishizawa M, Takahashi H, Ikeda K, Yokota S, Makishima M. The heat shock protein inhibitor KNK437 induces neurite outgrowth in PC12 cells. Neurosci Lett. 2006 Dec 27;410(3):212-7. Epub 2006 Oct 18. PubMed PMID: 17055158.
10: Ohnishi K, Yokota S, Takahashi A, Ohnishi T. Induction of radiation resistance by a heat shock protein inhibitor, KNK437, in human glioblastoma cells. Int J Radiat Biol. 2006 Aug;82(8):569-75. PubMed PMID: 16966184.
11: Sakurai H, Kitamoto Y, Saitoh J, Nonaka T, Ishikawa H, Kiyohara H, Shioya M, Fukushima M, Akimoto T, Hasegawa M, Nakano T. Attenuation of chronic thermotolerance by KNK437, a benzylidene lactam compound, enhances thermal radiosensitization in mild temperature hyperthermia combined with low dose-rate irradiation. Int J Radiat Biol. 2005 Sep;81(9):711-8. PubMed PMID: 16368649.
12: Ohnishi K, Takahashi A, Yokota S, Ohnishi T. Effects of a heat shock protein inhibitor KNK437 on heat sensitivity and heat tolerance in human squamous cell carcinoma cell lines differing in p53 status. Int J Radiat Biol. 2004 Aug;80(8):607-14. PubMed PMID: 15370972.
13: Koishi M, Yokota S, Mae T, Nishimura Y, Kanamori S, Horii N, Shibuya K, Sasai K, Hiraoka M. The effects of KNK437, a novel inhibitor of heat shock protein synthesis, on the acquisition of thermotolerance in a murine transplantable tumor in vivo. Clin Cancer Res. 2001 Jan;7(1):215-9. PubMed PMID: 11205912.
14: Yokota S, Kitahara M, Nagata K. Benzylidene lactam compound, KNK437, a novel inhibitor of acquisition of thermotolerance and heat shock protein induction in human colon carcinoma cells. Cancer Res. 2000 Jun 1;60(11):2942-8. PubMed PMID: 10850441.