NKH477 (Colforsin dapropate HCl) directly activates the catalytic unit of adenylate cyclase and increases intracellular cAMP. NKH477 is a forskolin analogue that improves heart failure primarily through beneficial effects on diastolic cardiac function. NKH477 is antiproliferation in vivo and inhibits acute rejection of orthotopic lung allografts in rats.

Physicochemical Properties

Molecular Formula	C28H45CLO8
Molecular Weight	545.11
Exact Mass	545.275
CAS #	138605-00-2
PubChem CID	444028
Appearance	White to off-white solid powder
Boiling Point	571.4ºC at 760mmHg
Flash Point	176ºC
Vapour Pressure	5.29E-16mmHg at 25°C
LogP	2.824
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	8
Heavy Atom Count	37
Complexity	933
Defined Atom Stereocenter Count	8
SMILES	C=C[C@@]1(C)CC(=O)[C@@]2([C@@]3(C)[C@H](CCC(C)(C)[C@@H]3[C@@H]([C@@H]([C@@]2(C)O1)OC(=O)C)OC(=O)CCN(C)C)O)O.Cl
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,1,11-15H2,2-9H31H/t18-,21-,22-,23-,25-,26-,27+,28-/m0./s1
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
Synonyms	NKH 477 NKH-477 NKH477
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.(3). This product is not stable in solution, please use freshly prepared working solution for optimal results.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vivo	In a dose-dependent manner, NKH477 (Colforsin dapropate hydrochloride) (oral; 1-3 mg/kg/day; days 3 and 5) improves lung allograft survival [1].
Animal Protocol	Animal/Disease Models: Specific pathogen-free inbred male Lewis rat (LEW), weighing 250 to 280 g [1] Doses: 1, 2 or 3 mg/kg/day Doses: Oral; daily; day 3 and Day 5 Experimental Results: Lung allograft survival was dose-dependently prolonged.
References	[1]. Antiproliferative effects of NKH477, a forskolin derivative, on cytokine profile in rat lung allografts. J Heart Lung Transplant. 2005 Apr;24(4):462-9.
Additional Infomation	Colforsin daropate hydrochloride is the hydrochloride salt of colforsin daropate. It is a drug used for the treatment of acute heart failure. It directly stimulates adenylate cyclase and produces positive inotropic and vasodilator effects accompanied by the increase in cellular cAMP. It has a role as an adenylate cyclase agonist, an antihypertensive agent, a cardiotonic drug and a vasodilator agent. It contains a colforsin daropate(1+). Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant Coleus forskohlii. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~228.90 mM) H2O : ~20 mg/mL (~36.62 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (3.81 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.81 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (3.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8345 mL	9.1725 mL	18.3449 mL
	5 mM	0.3669 mL	1.8345 mL	3.6690 mL
	10 mM	0.1834 mL	0.9172 mL	1.8345 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.