Conophylline is a vinca alkaloid found in the tropical plant Ervatamia microphylla. Conophylline is an inducer of pancreatic cell differentiation. Conophylline can inhibit HSCs and induce their apoptosis.

Physicochemical Properties

Molecular Formula	C44H50N4O10
Molecular Weight	794.8886
Exact Mass	794.352
CAS #	142741-24-0
PubChem CID	15226696
Appearance	Off-white to light yellow solid powder
Density	1.5±0.1 g/cm3
Index of Refraction	1.728
LogP	4.49
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	14
Rotatable Bond Count	8
Heavy Atom Count	58
Complexity	1890
Defined Atom Stereocenter Count	11
SMILES	O1C2([H])C([H])([H])N3C([H])([H])C([H])([H])C45C6C([H])=C7C(=C([H])C=6N([H])C4=C(C(=O)OC([H])([H])[H])C([H])([H])[C@](C([H])([H])C([H])([H])[H])(C12[H])C35[H])OC1([H])C([H])([C@@]2(C([H])([H])C([H])([H])[H])C([H])([H])C(C(=O)OC([H])([H])[H])=C3C4(C5=C([H])C(=C(C(=C5N3[H])OC([H])([H])[H])OC([H])([H])[H])O[H])C([H])([H])C([H])([H])N(C17[H])C24[H])O[H]
InChi Key	QZRIMAMDGWAHPQ-ATPAGDLWSA-N
InChi Code	InChI=1S/C44H50N4O10/c1-7-41-16-20(37(51)55-5)34-44(23-14-25(49)30(53-3)31(54-4)28(23)46-34)10-12-48(40(41)44)29-19-13-22-24(15-26(19)57-32(29)35(41)50)45-33-21(38(52)56-6)17-42(8-2)36-27(58-36)18-47-11-9-43(22,33)39(42)47/h13-15,27,29,32,35-36,39-40,45-46,49-50H,7-12,16-18H2,1-6H3/t27-,29-,32+,35-,36-,39+,40+,41-,42-,43+,44+/m1/s1
Chemical Name	dimethyl (2R,6R,11R,13S,14S,23S,24S,25S,36R,39R,40R)-14,25-diethyl-24,33-dihydroxy-31,32-dimethoxy-12,22-dioxa-1,9,18,29-tetrazadodecacyclo[23.13.1.16,9.02,23.03,21.05,19.06,17.011,13.028,36.030,35.036,39.014,40]tetraconta-3,5(19),16,20,27,30,32,34-octaene-16,27-dicarboxylate
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
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 Vitro	Activin-inducing activity is eliminated by conophylline (100 ng/mL; 48 hours), although cell-inducing activity is still present [1]. Conophylline (100 ng/mL; 72 hours) is an inducer of AR42J cell activity, which means that it activates p38 mitogen-activated protein, which in turn causes AR42J cell secretion and raises the expression of Neurogenin-3 [1]. Conophylline decreases α-SMA in HSC and Lx-2 cells. It also encourages caspase-3 activation and increases Lx-2 cell expression [2]. Cell
ln Vivo	In vivo hepatic fibrosis caused by TAA is reduced by conophylline (0.9 mg/kg; epidermal; once daily; 12 weeks) [2].
Cell Assay	Apoptosis Analysis[2] Cell Types: Expression of Lx-1[2]. 2 Cell Tested Concentrations: 12 hrs (hours) Incubation Duration: 0.1 μg/ml Experimental Results: Induction of apoptosis Western Blot analysis [2] Cell Types: Lx-2 Cell Tested Concentrations: 0.1 μg/ml Incubation Duration: 15 minutes, 30 minutes, 60 minutes, 120 min Experimental Results: Increased phospho-JNK.
Animal Protocol	Animal/Disease Models: SD (SD (Sprague-Dawley)) rat (70-80 g) [2] Doses: 0.9 mg/kg Route of Administration: oral; daily; 12-week Experimental Results: TAA-induced liver fibrosis formation was attenuated.
References	[1]. Kojima I, et al. Conophylline: a novel differentiation inducer for pancreatic beta cells. Int J Biochem Cell Biol. 2006;38(5-6):923-30. [2]. Kubo N, et al. Conophylline suppresses hepatic stellate cells and attenuates thioacetamide-induced liver fibrosis in rats. Liver Int. 2014 Aug;34(7):1057-67.
Additional Infomation	Conophylline has been reported in Tabernaemontana glandulosa and Tabernaemontana divaricata with data available.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.2580 mL	6.2902 mL	12.5804 mL
	5 mM	0.2516 mL	1.2580 mL	2.5161 mL
	10 mM	0.1258 mL	0.6290 mL	1.2580 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.