NNC 55-0396 HCl | CAS#357400-13-6 | T-type calcium channel blocker

MedKoo Cat#: 526807 | Name: NNC 55-0396 HCl

Description:

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

NNC 55-0396 is a T-type calcium channel blocker. NNC 55-0396 inhibits angiogenesis via suppression of hypoxia-inducible factor-1α signal transduction. NNC 55-0396 suppressed mitochondrial reactive oxygen species-mediated HIF-1α expression as well as stabilization by inhibiting protein synthesis in a dose-dependent manner. NNC 55-0396 inhibited tumor-induced angiogenesis in vitro and in vivo by suppressing HIF-1α stability. NNC 55-0396 could be a potential therapeutic drug candidate for cancer treatment.

Chemical Structure

NNC 55-0396 HCl

CAS#357400-13-6 (HCl)

Theoretical Analysis

MedKoo Cat#: 526807

Name: NNC 55-0396 HCl

CAS#: 357400-13-6 (HCl)

Chemical Formula: C30H40Cl2FN3O2

Exact Mass: 0.0000

Molecular Weight: 564.57

Elemental Analysis: C, 63.82; H, 7.14; Cl, 12.56; F, 3.37; N, 7.44; O, 5.67

Price and Availability

Size	Price	Availability
25mg	USD 550.00	2 Weeks
50mg	USD 950.00	2 Weeks
100mg	USD 1,650.00	2 Weeks
200mg	USD 2,950.00	2 Weeks
500mg	USD 5,150.00	2 Weeks
1g	USD 7,150.00	2 Weeks

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Related CAS #

357400-14-7 (free base) 357400-13-6 (HCl)

Synonym

NNC 55-0396; NNC55-0396; NNC-55-0396; NNC-550396; NNC550396; NNC 550396; NNC 55-0396 dihydrochloride

IUPAC/Chemical Name

(1S,2S)-2-(2-((3-(1H-benzo[d]imidazol-2-yl)propyl)(methyl)amino)ethyl)-6-fluoro-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl cyclopropanecarboxylate dihydrochloride

InChi Key

BCCQNBXHUMKLFW-HNQRYHMESA-N

InChi Code

InChI=1S/C30H38FN3O2.2ClH/c1-20(2)28-24-13-12-23(31)19-22(24)14-15-30(28,36-29(35)21-10-11-21)16-18-34(3)17-6-9-27-32-25-7-4-5-8-26(25)33-27;;/h4-5,7-8,12-13,19-21,28H,6,9-11,14-18H2,1-3H3,(H,32,33);2*1H/t28-,30-;;/m0../s1

SMILES Code

CC([C@H]1C2=C(C=C(F)C=C2)CC[C@]1(OC(C3CC3)=O)CCN(CCCC4=NC5=CC=CC=C5N4)C)C.Cl.Cl

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 water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in water

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:

NNC 55-0396 is a highly selective T-type calcium channel blocker with an IC50 value of 6.8 μM for Cav3.1 T-type channels.

In vitro activity:

The present study modified the structure of mibefradil to develop a nonhydrolyzable analog, (1S, 2S)-2-(2-(N-[(3-benzimidazol-2-yl)propyl]-N-methylamino)ethyl)-6-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphtyl cyclopropanecarboxylate dihydrochloride (NNC 55-0396), that exerts a selective inhibitory effect on T-type channels. The acute IC(50) of NNC 55-0396 to block recombinant alpha(1)G T-type channels in human embryonic kidney 293 cells was approximately 7 microM, whereas 100 microM NNC 55-0396 had no detectable effect on high-voltage-activated channels in INS-1 cells. Reference: J Pharmacol Exp Ther. 2004 Apr;309(1):193-9. https://pubmed.ncbi.nlm.nih.gov/14718587/

In vivo activity:

To assess for a potential interaction with harmaline, mice were given the drugs, followed by harmaline or vehicle, and tested 30min later in the inverted wire grid test. Mibefradil exacerbated, whereas NNC 55-0396 ameliorated harmaline-induced test deficits. In the GABAA α1-null model, NNC 55-0396 but not mibefradil, (each at 20mg/kg), suppressed tremor while NNC 55-0396 at 12.5mg/kg suppressed harmaline-induced tremor by half by 20-100min, whereas mibefradil at the same dose did not significantly affect tremor. Reference: Eur J Pharmacol. 2011 May 20;659(1):30-6. https://pubmed.ncbi.nlm.nih.gov/21256842/

	Solvent	mg/mL	mM
Solubility
	Water	14.1	25.00
	DMF	30.0	53.14
	DMSO	65.0	115.13
	Ethanol	30.0	53.14
	Ethanol:PBS (pH 7.2) (1:3)	0.3	0.44

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 564.57 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. Son YK, Hong DH, Li H, Kim DJ, Na SH, Park H, Jung WK, Choi IW, Park WS. Ca2+ channel inhibitor NNC 55-0396 inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells. J Pharmacol Sci. 2014;125(3):312-9. doi: 10.1254/jphs.14054fp. Epub 2014 Jul 1. PMID: 24989838. 2. Huang L, Keyser BM, Tagmose TM, Hansen JB, Taylor JT, Zhuang H, Zhang M, Ragsdale DS, Li M. NNC 55-0396 [(1S,2S)-2-(2-(N-[(3-benzimidazol-2-yl)propyl]-N-methylamino)ethyl)-6-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphtyl cyclopropanecarboxylate dihydrochloride]: a new selective inhibitor of T-type calcium channels. J Pharmacol Exp Ther. 2004 Apr;309(1):193-9. doi: 10.1124/jpet.103.060814. Epub 2004 Jan 12. PMID: 14718587. 3. Kim KH, Kim D, Park JY, Jung HJ, Cho YH, Kim HK, Han J, Choi KY, Kwon HJ. NNC 55-0396, a T-type Ca2+ channel inhibitor, inhibits angiogenesis via suppression of hypoxia-inducible factor-1α signal transduction. J Mol Med (Berl). 2015 May;93(5):499-509. doi: 10.1007/s00109-014-1235-1. Epub 2014 Dec 4. PMID: 25471482. 4. Quesada A, Bui PH, Homanics GE, Hankinson O, Handforth A. Comparison of mibefradil and derivative NNC 55-0396 effects on behavior, cytochrome P450 activity, and tremor in mouse models of essential tremor. Eur J Pharmacol. 2011 May 20;659(1):30-6. doi: 10.1016/j.ejphar.2011.01.004. Epub 2011 Jan 21. PMID: 21256842; PMCID: PMC3988263.

In vitro protocol:

In vivo protocol:

1. Kim KH, Kim D, Park JY, Jung HJ, Cho YH, Kim HK, Han J, Choi KY, Kwon HJ. NNC 55-0396, a T-type Ca2+ channel inhibitor, inhibits angiogenesis via suppression of hypoxia-inducible factor-1α signal transduction. J Mol Med (Berl). 2015 May;93(5):499-509. doi: 10.1007/s00109-014-1235-1. Epub 2014 Dec 4. PMID: 25471482. 2. Quesada A, Bui PH, Homanics GE, Hankinson O, Handforth A. Comparison of mibefradil and derivative NNC 55-0396 effects on behavior, cytochrome P450 activity, and tremor in mouse models of essential tremor. Eur J Pharmacol. 2011 May 20;659(1):30-6. doi: 10.1016/j.ejphar.2011.01.004. Epub 2011 Jan 21. PMID: 21256842; PMCID: PMC3988263.

1: Huang W, Lu C, Wu Y, Ouyang S, Chen Y. T-type calcium channel antagonists, mibefradil and NNC-55-0396 inhibit cell proliferation and induce cell apoptosis in leukemia cell lines. J Exp Clin Cancer Res. 2015 May 21;34:54. doi: 10.1186/s13046-015-0171-4. PubMed PMID: 25989794; PubMed Central PMCID: PMC4443536. 2: Fernández-Morales JC, Fernando Padín J, Vestring S, Musial DC, de Diego AM, García AG. Blockade by NNC 55-0396, mibefradil, and nickel of calcium and exocytotic signals in chromaffin cells: implications for the regulation of hypoxia-induced secretion at early life. Eur J Pharmacol. 2015 Mar 15;751:1-12. doi: 10.1016/j.ejphar.2015.01.025. Epub 2015 Jan 23. PubMed PMID: 25622555. 3: Kim KH, Kim D, Park JY, Jung HJ, Cho YH, Kim HK, Han J, Choi KY, Kwon HJ. NNC 55-0396, a T-type Ca2+ channel inhibitor, inhibits angiogenesis via suppression of hypoxia-inducible factor-1α signal transduction. J Mol Med (Berl). 2015 May;93(5):499-509. doi: 10.1007/s00109-014-1235-1. Epub 2014 Dec 4. PubMed PMID: 25471482. 4: Son YK, Hong da H, Li H, Kim DJ, Na SH, Park H, Jung WK, Choi IW, Park WS. Ca2+ channel inhibitor NNC 55-0396 inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells. J Pharmacol Sci. 2014;125(3):312-9. Epub 2014 Jul 1. PubMed PMID: 24989838. 5: Quesada A, Bui PH, Homanics GE, Hankinson O, Handforth A. Comparison of mibefradil and derivative NNC 55-0396 effects on behavior, cytochrome P450 activity, and tremor in mouse models of essential tremor. Eur J Pharmacol. 2011 May 20;659(1):30-6. doi: 10.1016/j.ejphar.2011.01.004. Epub 2011 Jan 21. PubMed PMID: 21256842; PubMed Central PMCID: PMC3988263. 6: Li M, Hansen JB, Huang L, Keyser BM, Taylor JT. Towards selective antagonists of T-type calcium channels: design, characterization and potential applications of NNC 55-0396. Cardiovasc Drug Rev. 2005 Summer;23(2):173-96. PubMed PMID: 16007233. 7: Huang L, Keyser BM, Tagmose TM, Hansen JB, Taylor JT, Zhuang H, Zhang M, Ragsdale DS, Li M. NNC 55-0396 [(1S,2S)-2-(2-(N-[(3-benzimidazol-2-yl)propyl]-N-methylamino)ethyl)-6-fluoro-1,2, 3,4-tetrahydro-1-isopropyl-2-naphtyl cyclopropanecarboxylate dihydrochloride]: a new selective inhibitor of T-type calcium channels. J Pharmacol Exp Ther. 2004 Apr;309(1):193-9. Epub 2004 Jan 12. PubMed PMID: 14718587.