KNK437 | CAS#218924-25-5 | pan-HSP inhibitor

KNK437
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 558221

CAS#: 218924-25-5

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.

Chemical Structure

KNK437

CAS# 218924-25-5

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 558221
Name: KNK437
CAS#: 218924-25-5
Chemical Formula: C13H11NO4
Exact Mass: 245.07
Molecular Weight: 245.234
Elemental Analysis: C, 63.67; H, 4.52; N, 5.71; O, 26.10

Price and Availability

Size	Price	Availability
50mg	USD 450	2 Weeks
100mg	USD 750	2 Weeks
200mg	USD 1350	2 Weeks
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

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

More Info:

Product Data:

Product Data

Instruction:

View handling instruction

Biological target:	KNK437 is a HSP inhibitor, and inhibits the induction of HSP105, HSP70, and HSP40.
In vitro activity:	KNK437 and quercetin inhibited thermotolerance in a dose-dependent manner in PC-3 cells. KNK437 and quercetin decreased heat-induced accumulation of Hsp70 mRNA and protein in PC-3 and LNCaP cells. KNK437 and quercetin pretreatment enhanced the apoptotic effect of hyperthermia in both cells. Reference: Int J Hyperthermia. 2011;27(1):63-73. https://pubmed.ncbi.nlm.nih.gov/21204621/
In vivo activity:	TBD

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMF	10.0	40.78
	DMF:PBS (pH 7.2) (1:5)	0.1	0.41
	DMSO	19.4	79.18

Preparing Stock Solutions

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

Formulation protocol:	1. 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. PMID: 21204621. 2. 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. doi: 10.1080/02656730601074375. PMID: 17391001.
In vitro protocol:	1. 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. PMID: 21204621. 2. 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. doi: 10.1080/02656730601074375. PMID: 17391001.
In vivo protocol:	TBD

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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.

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