| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
HA-1004 targets cyclic GMP-dependent protein kinase (PKG) and cyclic AMP-dependent protein kinase (PKA) with Ki values of 1.4 and 2.3 µM, respectively. It also inhibits PKC and blocks intracellular calcium mobilization. Additional targets include ERK, calcium channels, and cyclic GMP-AMP synthase. It has the weakest affinity for protein kinase C among isoquinoline sulfonamide inhibitors.
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|---|---|
| ln Vitro |
In vitro, HA-1004 inhibits PKA with an IC50 of approximately 5.2 µM. It inhibits PKG with a Ki of 1.4 µM and PKA with a Ki of 2.3 µM. It affects PKC with an IC50 of 12 µM. HA-1004 induces relaxation of isolated rabbit aortic strips precontracted with histamine, serotonin, A23187, angiotensin II, or prostaglandin F2α with EC50s of 0.32-0.63 µM, and with phenylephrine with or without calcium with EC50s of 2.3 and 0.5 µM, respectively. It inhibits calcitriol-induced differentiation of HL-60 cells with an IC50 of approximately 170 µM.
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| ln Vivo |
In vivo, intravenous administration of HA-1004 effectively blocks bronchoconstriction induced by intravenous histamine and methacholine in guinea pigs. HA-1004 also reverses histamine-induced bronchospasm. Intratracheal administration of HA-1004 inhibits histamine-induced bronchoconstriction without affecting blood pressure at a dose of 0.1 mg per animal. In newborn lambs, intravenous infusions of HA-1004 (0.1-2.0 mg/kg) selectively attenuate pulmonary hypertension. In morphine-withdrawn rats, HA-1004 (40 nmol/day via micropump at 1 µL/h) phosphorylates ERK1/2 and TH, preventing the rise in NA turnover.
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| Enzyme Assay |
PKA inhibition is measured using a standard kinase assay with recombinant PKA enzyme and a peptide substrate. The reaction mixture contains ATP, substrate, and varying concentrations of HA-1004. The percent inhibition is plotted against the logarithm of inhibitor concentration, and IC50 values are determined by non-linear regression analysis of sigmoidal dose-response curves. The assay should be performed at ATP concentrations close to the Km of the enzyme for physiologically relevant IC50 values.
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| Cell Assay |
In vitro cell assays use cell lines treated with HA-1004 at concentrations ranging from 0.1 to 50 µM. Cellular effects are assessed by measuring PKA substrate phosphorylation, ERK1/2 phosphorylation, or calcium mobilization. For HL-60 cell differentiation studies, cells are treated with calcitriol and HA-1004 (up to 320 µM), and differentiation markers are assessed by flow cytometry.
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| Animal Protocol |
In vivo studies use guinea pigs for bronchoconstriction models, with HA-1004 administered intravenously or intratracheally. For pulmonary hypertension studies, newborn lambs receive intravenous infusions at 0.1-2.0 mg/kg. For morphine withdrawal studies, rats receive HA-1004 (40 nmol/day) via osmotic micropump at a flow rate of 1 µL/h.
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| References |
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| Molecular Formula |
C12H17CL2N5O2S
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|---|---|
| Molecular Weight |
366.266678571701
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| Exact Mass |
365.048
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| CAS # |
92564-08-4
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| Related CAS # |
91742-10-8;92564-34-6 (HCl);92564-08-4 (2HCl);
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| PubChem CID |
16760499
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| Appearance |
Typically exists as solid at room temperature
|
| tPSA |
132
|
| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
22
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| Complexity |
441
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.Cl.S(C1=CC=CC2C=NC=CC1=2)(NCC/N=C(\N)/N)(=O)=O
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| InChi Key |
PMTUBVLLVFJRLK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H15N5O2S.2ClH/c13-12(14)16-6-7-17-20(18,19)11-3-1-2-9-8-15-5-4-10(9)11;;/h1-5,8,17H,6-7H2,(H4,13,14,16);2*1H
|
| Chemical Name |
2-[2-(isoquinolin-5-ylsulfonylamino)ethyl]guanidine;dihydrochloride
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| HS Tariff Code |
2934.99.9001
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| 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)
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| 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
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|---|---|
| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7302 mL | 13.6511 mL | 27.3023 mL | |
| 5 mM | 0.5460 mL | 2.7302 mL | 5.4605 mL | |
| 10 mM | 0.2730 mL | 1.3651 mL | 2.7302 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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