NKH477 | CAS#138605-00-2

MedKoo Cat#: 532351 | Name: NKH477

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Description:

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

NKH477 is a potent activator of adenylyl cyclase. NKH477 shows some selectivity for cardiac (type V) adenylyl cyclase. NKH477 stimulates bronchodilation (EC50 = 32.6 nM) and is an orally active potent positive chronotrope and hypotensive agent in vivo.

Chemical Structure

NKH477

CAS#138605-00-2

Theoretical Analysis

MedKoo Cat#: 532351

Name: NKH477

CAS#: 138605-00-2

Chemical Formula: C28H45ClO8

Exact Mass: 544.2803

Molecular Weight: 545.11

Elemental Analysis: C, 61.70; H, 8.32; Cl, 6.50; O, 23.48

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 350.00	2 Weeks
10mg	USD 600.00	2 Weeks

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Synonym

NKH477; NKH 477; NKH-477; Colforsin daropate HCl; Colforsin daropate hydrochloride; Adehl HCl; Colforsin Dapropate HCl; Colforsin Daropate HCl

IUPAC/Chemical Name

(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-5-(acetyloxy)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-dodecahydro-1H-naphtho[2,1-b]pyran-6-yl 4-methylpentanoate hydrochloride

InChi Key

LNEICJSEZPSKSJ-RPBMHHKSSA-N

InChi Code

InChI=1S/C28H44O8.ClH/c1-10-25(7)15-19(31)28(33)26(8)18(30)13-14-24(5,6)22(26)21(35-20(32)12-11-16(2)3)23(34-17(4)29)27(28,9)36-25;/h10,16,18,21-23,30,33H,1,11-15H2,2-9H3;1H/t18-,21-,22-,23-,25-,26-,27+,28-;/m0./s1

SMILES Code

CC(C)CCC(O[C@@H]([C@@]1([H])C(C)(C)CC[C@H](O)[C@@]12C)[C@H](OC(C)=O)[C@]3(C)[C@]2(O)C(C[C@](C)(C=C)O3)=O)=O.[H]Cl

Appearance

Solid powder

Purity

>95% (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).

HS Tariff Code

2934.99.9001

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Product Data

Product Data

Instruction

View handling instruction

Biological target:

NKH477 (Colforsin dapropate hydrochloride) directly activates the catalytic unit of adenylate cyclase.

In vitro activity:

NKH477 is a direct adenylate cyclase activator derived from forskolin and now under clinical investigation as a positive inotropic agent. Addition of NKH477 to the culture medium suppressed the generation of CTL, T cell proliferation in MLR, and production of IL-2 in MLR and in mitogen response. Reference: Clin Immunol Immunopathol. 1996 Apr;79(1):25-35. https://pubmed.ncbi.nlm.nih.gov/8612348/

In vivo activity:

Left lungs were transplanted orthotopically from Brown-Norway donors to Lewis recipients. Recipient rats were untreated or treated daily with different doses of NKH477. NKH477 significantly extended allograft survival time in a dose-dependent manner and reduced histopathological rejection. Treatment with NKH477 inhibited IFN-gamma and IL-10 expression, whereas expression of these cytokines were markedly upregulated in the untreated allografts. Reference: J Heart Lung Transplant. 2005 Apr;24(4):462-9. https://pubmed.ncbi.nlm.nih.gov/15797749/

	Solvent	mg/mL	mM
Solubility
	DMF	20.0	36.69
	DMSO	77.5	142.17
	DMSO:PBS (pH 7.2) (1:1)	0.5	0.92
	Ethanol	2.5	4.59
	Water	20.9	38.38

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 545.11 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. Furukawa Y, Matsumori A, Hirozane T, Matsui S, Sato Y, Ono K, Sasayama S. Immunomodulation by an adenylate cyclase activator, NKH477, in vivo and vitro. Clin Immunol Immunopathol. 1996 Apr;79(1):25-35. doi: 10.1006/clin.1996.0047. PMID: 8612348. 2. Ito S, Suzuki S, Itoh T. Effects of a water-soluble forskolin derivative (NKH477) and a membrane-permeable cyclic AMP analogue on noradrenaline-induced Ca2+ mobilization in smooth muscle of rabbit mesenteric artery. Br J Pharmacol. 1993 Nov;110(3):1117-25. doi: 10.1111/j.1476-5381.1993.tb13930.x. PMID: 8298800; PMCID: PMC2175778. 3. Nakashima S, Morikawa M, Komatsu K, Matsuura A, Sato N, Abe T. Antiproliferative effects of NKH477, a forskolin derivative, on cytokine profile in rat lung allografts. J Heart Lung Transplant. 2005 Apr;24(4):462-9. doi: 10.1016/j.healun.2004.02.011. PMID: 15797749. 4. Hosono M, Takahira T, Fujita A, Fujihara R, Ishizuka O, Tatee T, Nakamura K. Cardiovascular and adenylate cyclase stimulant properties of NKH477, a novel water-soluble forskolin derivative. J Cardiovasc Pharmacol. 1992 Apr;19(4):625-34. doi: 10.1097/00005344-199204000-00021. PMID: 1380607.

In vitro protocol:

In vivo protocol:

1. Nakashima S, Morikawa M, Komatsu K, Matsuura A, Sato N, Abe T. Antiproliferative effects of NKH477, a forskolin derivative, on cytokine profile in rat lung allografts. J Heart Lung Transplant. 2005 Apr;24(4):462-9. doi: 10.1016/j.healun.2004.02.011. PMID: 15797749. 2. Hosono M, Takahira T, Fujita A, Fujihara R, Ishizuka O, Tatee T, Nakamura K. Cardiovascular and adenylate cyclase stimulant properties of NKH477, a novel water-soluble forskolin derivative. J Cardiovasc Pharmacol. 1992 Apr;19(4):625-34. doi: 10.1097/00005344-199204000-00021. PMID: 1380607.

1: Nakashima S, Morikawa M, Komatsu K, Matsuura A, Sato N, Abe T. Antiproliferative effects of NKH477, a forskolin derivative, on cytokine profile in rat lung allografts. J Heart Lung Transplant. 2005 Apr;24(4):462-9. PubMed PMID: 15797749. 2: Morikawa M, Nakashima S, Komatsu K, Abe T. NKH477, a forskolin derivative, exerts an antiproliferative effect in vivo with an altered cytokine profile in rat recipients of orthotopic lung allografts. J Heart Lung Transplant. 2001 Feb;20(2):254. PubMed PMID: 11250507. 3: Hara S, Tanahashi M, Yoshida M, Suzuki-Kusaba M, Hisa H, Satoh S. Effects of NKH477 on endothelin-1-induced renal responses in anaesthetized dogs. Clin Exp Pharmacol Physiol. 2000 Jul;27(7):513-5. PubMed PMID: 10874508. 4: Tanahashi M, Hara S, Saitoh K, Yoshida M, Suzuki-Kusaba M, Hisa H, Satoh S. Effects of NKH477 on renal nerve stimulation-induced responses in anesthetized dogs. Eur J Pharmacol. 1999 Nov 12;384(1):31-6. PubMed PMID: 10611416. 5: Tanahashi M, Hara S, Yoshida M, Suzuki-Kusaba M, Yokoyama H, Hosono M, Hisa H, Satoh S. Effects of NKH477 on renal functions and cyclic AMP production in anesthetized dogs. Eur J Pharmacol. 1999 May 21;372(3):253-9. PubMed PMID: 10395020. 6: Morinobu S, Fujimaki K, Okuyama N, Takahashi M, Duman RS. Stimulation of adenylyl cyclase and induction of brain-derived neurotrophic factor and TrkB mRNA by NKH477, a novel and potent forskolin derivative. J Neurochem. 1999 May;72(5):2198-205. PubMed PMID: 10217303. 7: Satake K, Takagi K, Kodama I, Honjo H, Toyama J, Shibata S. Relaxant effects of NKH477, a new water-soluble forskolin derivative, on guinea-pig tracheal smooth muscle: the role of Ca2+-activated K+ channels. Br J Pharmacol. 1998 Feb;123(4):753-61. PubMed PMID: 9517396; PubMed Central PMCID: PMC1565213. 8: Koshika T, Nagayama T, Iizuka Y, Kimura T, Satoh S. Effects of NKH477, a forskolin derivative, and dibutyryl-cyclic AMP on adrenal catecholamine release in response to splanchnic nerve stimulation, acetylcholine, DMPP and muscarine in anesthetized dogs. Fundam Clin Pharmacol. 1997;11(6):512-8. PubMed PMID: 9444518. 9: Maeda H, Ozawa H, Saito T, Irie T, Takahata N. Potential antidepressant properties of forskolin and a novel water-soluble forskolin (NKH477) in the forced swimming test. Life Sci. 1997;61(25):2435-42. PubMed PMID: 9416762. 10: Ishizuka O, Fujita A, Kanbe E, Noguchi M, Hosono M, Sakitama K. [Effectiveness of NKH477, a novel forskolin derivative, in rat cardiac preparations with desensitized beta-adrenoceptors]. Nihon Yakurigaku Zasshi. 1996 Jul;108(1):23-30. Japanese. PubMed PMID: 8810493. 11: Furukawa Y, Matsumori A, Hirozane T, Matsui S, Sato Y, Ono K, Sasayama S. Immunomodulation by an adenylate cyclase activator, NKH477, in vivo and vitro. Clin Immunol Immunopathol. 1996 Apr;79(1):25-35. PubMed PMID: 8612348. 12: Sanbe A, Takeo S. Effects of NKH477, a water-soluble forskolin derivative, on cardiac function in rats with chronic heart failure after myocardial infarction. J Pharmacol Exp Ther. 1995 Jul;274(1):120-6. Erratum in: J Pharmacol Exp Ther 1996 Jan;276(1):352. PubMed PMID: 7616388. 13: Iida M, Fujita N, Hosono M, Sukenaga Y. Bronchodilator and cardiovascular effects of NKH477, a novel water-soluble forskolin derivative, in guinea pigs. Jpn J Pharmacol. 1995 Jul;68(3):245-53. PubMed PMID: 7474547. 14: Mori M, Takeuchi M, Takaoka H, Hata K, Hayashi Y, Yokoyama M. Effect of NKH477, a new water-soluble forskolin derivative, on arterial-ventricular coupling and mechanical energy transduction in patients with left ventricular systolic dysfunction: comparison with dobutamine. J Cardiovasc Pharmacol. 1994 Aug;24(2):310-6. PubMed PMID: 7526066. 15: Hirasawa A, Awaji T, Hosono M, Haruno A, Hashimoto K. Effects of a new forskolin derivative, NKH477, on canine ventricular arrhythmia models. J Cardiovasc Pharmacol. 1993 Dec;22(6):847-51. PubMed PMID: 7509903. 16: Ito S, Suzuki S, Itoh T. Effects of a water-soluble forskolin derivative (NKH477) and a membrane-permeable cyclic AMP analogue on noradrenaline-induced Ca2+ mobilization in smooth muscle of rabbit mesenteric artery. Br J Pharmacol. 1993 Nov;110(3):1117-25. PubMed PMID: 8298800; PubMed Central PMCID: PMC2175778. 17: Ishizuka O, Hosono M, Nakamura K. Profile of cardiovascular effects of NKH477, a novel forskolin derivative, assessed in isolated, blood-perfused dog heart preparations: comparison with isoproterenol. J Cardiovasc Pharmacol. 1992 Aug;20(2):261-7. PubMed PMID: 1381017. 18: Shafiq J, Suzuki S, Itoh T, Kuriyama H. Mechanisms of vasodilation induced by NKH477, a water-soluble forskolin derivative, in smooth muscle of the porcine coronary artery. Circ Res. 1992 Jul;71(1):70-81. PubMed PMID: 1318797. 19: Fujita A, Takahira T, Hosono M, Nakamura K. Improvement of drug-induced cardiac failure by NKH477, a novel forskolin derivative, in the dog heart-lung preparation. Jpn J Pharmacol. 1992 Apr;58(4):375-81. PubMed PMID: 1405034. 20: Hosono M, Takahira T, Fujita A, Fujihara R, Ishizuka O, Tatee T, Nakamura K. Cardiovascular and adenylate cyclase stimulant properties of NKH477, a novel water-soluble forskolin derivative. J Cardiovasc Pharmacol. 1992 Apr;19(4):625-34. PubMed PMID: 1380607.