 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C61H93N19O15S |
| Molecular Weight | 1364.57 |
| Exact Mass | 1363.68 |
| CAS # | 138614-30-9 |
| Related CAS # | Icatibant;130308-48-4 |
| PubChem CID | 6918172 |
| Appearance | White to off-white solid powder |
| Density | 1.6g/cm3 |
| LogP | 1.676 |
| Hydrogen Bond Donor Count | 16 |
| Hydrogen Bond Acceptor Count | 20 |
| Rotatable Bond Count | 30 |
| Heavy Atom Count | 96 |
| Complexity | 2750 |
| Defined Atom Stereocenter Count | 12 |
| SMILES | CC(=O)O.C1CC[C@H]2[C@@H](C1)C[C@H](N2C(=O)[C@H]3CC4=CC=CC=C4CN3C(=O)[C@H](CO)NC(=O)[C@H](CC5=CC=CS5)NC(=O)CNC(=O)[C@@H]6C[C@H](CN6C(=O)[C@@H]7CCCN7C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](CCCN=C(N)N)N)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O |
| InChi Key | HKMZRZUEADSZDQ-DZJWSCHMSA-N |
| InChi Code | InChI=1S/C59H89N19O13S.C2H4O2/c60-37(14-5-19-67-57(61)62)48(82)72-38(15-6-20-68-58(63)64)52(86)75-22-8-18-43(75)54(88)77-30-35(80)26-44(77)50(84)70-28-47(81)71-40(27-36-13-9-23-92-36)49(83)74-41(31-79)53(87)76-29-34-12-2-1-10-32(34)24-46(76)55(89)78-42-17-4-3-11-33(42)25-45(78)51(85)73-39(56(90)91)16-7-21-69-59(65)66;1-2(3)4/h1-2,9-10,12-13,23,33,35,37-46,79-80H,3-8,11,14-22,24-31,60H2,(H,70,84)(H,71,81)(H,72,82)(H,73,85)(H,74,83)(H,90,91)(H4,61,62,67)(H4,63,64,68)(H4,65,66,69);1H3,(H,3,4)/t33-,35+,37+,38-,39-,40-,41-,42-,43-,44-,45-,46+;/m0./s1 |
| Chemical Name | (2S)-2-[[(2S,3aS,7aS)-1-[(3R)-2-[(2S)-2-[[(2S)-2-[[2-[[(2S,4R)-1-[(2S)-1-[(2S)-2-[[(2R)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]-4-hydroxypyrrolidine-2-carbonyl]amino]acetyl]amino]-3-thiophen-2-ylpropanoyl]amino]-3-hydroxypropanoyl]-3,4-dihydro-1H-isoquinoline-3-carbonyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoic acid;acetic acid |
| 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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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
| Targets | Bradykinin B2 Receptor (B2R) |
| ln Vivo | Angiotensin III, but not angiotensin II (contraction mediated by the angiotensin AT1 receptor), Lys-des-Arg9-Bradykinin, or des-Arg9-Bradykinin (activity mediated by the bradykinin B1 receptor) are all potentiated by isatin acetate (10–30 μM)[3]. |
| Animal Protocol |
Animal/Disease Models: Female mice of the CBA/J (H-2k) strain[2]. Doses: 0.06, 0.3, or 1.5 mg/kg. Route of Administration: subcutaneous (sc) administration twice (two times) daily. Experimental Results: The length of the large intestine was 93.6± 6.8 mm with the 1.5 mg/kg dosage and 94.0±4.1 mm with the 0.3 mg/kg dosage, showing a significant preventive effect on shortening. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the excretion of icatibant into breastmilk. Because icatibant is a protein molecule with a molecular weight of 1305 Da, the amount in milk is likely to be very low. It is also likely to be partially destroyed in the infant's gastrointestinal tract and absorption by the infant is probably minimal. One patient reportedly used the drug safely during breastfeeding. Waiting 6 hours after a dose before breastfeeding should minimize the amount of drug excreted into breastmilk. ◉ Effects in Breastfed Infants A woman with hereditary angioedema began using icatibant 30 mg subcutaneously as needed for hereditary angioedema attacks when her breastfed infant was 4 months of age and continued breastfeeding for 1 year while taking icatibant. Doses were injected at night before the infant’s longest sleep period and breastfeeding was not resumed until at least 6 hours after a dose. In cases of swelling of the face and neck and abdominal pain, icatibant was immediately self-administered, and formula was given instead of breastmilk. In her second pregnancy 2 years later, she used C1 esterase inhibitor until the infant was 1 month of age, when she resumed icatibant therapy. . ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. |
| References |
[1]. Hoe 140 a new potent and long acting bradykinin-antagonist: in vitro studies. Br J Pharmacol. 1991 Mar;102(3):769-73. [2]. Effect of Icatibant, a Bradykinin B2 Receptor Antagonist, on the Development of Experimental Ulcerative Colitis in Mice. Dig Dis Sci. 1999 Apr;44(4):845-51. [3]. Marie-Thérèse Bawolak, et al The Bradykinin B2 Receptor Antagonist Icatibant (Hoe 140) Blocks Aminopeptidase N at Micromolar Concentrations: Off-Target Alterations of Signaling Mediated by the Bradykinin B1 and Angiotensin Receptors. Eur J Pharmacol. 2006 Dec 3;551(1-3):108-11. |
| Additional Infomation |
Icatibant Acetate is the acetate salt form of icatibant, an antagonist of the human bradykinin B2 receptor (B2R), that can be used for the treatment of hereditary angioedema (HAE). Upon administration, icatibant targets and binds to B2R, thereby preventing bradykinin from binding to the B2R. This may prevent bradykinin/B2R-mediated vasodilation, the resulting increase in vascular permeability, and the swelling, inflammation, and pain associated with HAE. This may also prevent or improve pulmonary edema not associated with HAE and improve the associated decrease in blood oxygen levels. See also: Icatibant (has active moiety). Drug Indication Firazyr is indicated for symptomatic treatment of acute attacks of hereditary angioedema (HAE) in adults (with C1-esterase-inhibitor deficiency). Icatibant Accord is indicated for symptomatic treatment of acute attacks of hereditary angioedema (HAE) in adults, adolescents and children aged 2 years and older, with C1 esterase inhibitor deficiency. Treatment of hereditary angioedema |
Solubility Data
| Solubility (In Vitro) | DMSO: 100 mg/mL (73.28 mM) |
| 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 | 0.7328 mL | 3.6642 mL | 7.3283 mL | |
| 5 mM | 0.1466 mL | 0.7328 mL | 1.4657 mL | |
| 10 mM | 0.0733 mL | 0.3664 mL | 0.7328 mL |