AB023 A
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| Category | Antibiotics |
| Catalog number | BBF-03184 |
| CAS | 141443-39-2 |
| Molecular Weight | 550.72 |
| Molecular Formula | C31H50O8 |
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Description
AB023 A is a pentaene macrolide antibiotic produced by Streptomyces sp. SD581 and K9925278. It has the activity against several pathogenic fungi such as black koji and Candida albicans. The MIC of Botrytis cinerea is 5 μg/mL.
Specification
| Synonyms | Oxacyclooctacosa-17,19,21,23,25-pentaen-2-one, 4,6,10,12,14,16-hexahydroxy-3,15,27,28-tetramethyl- |
| IUPAC Name | (17E,19E,21E,23E,25E)-4,6,10,12,14,16-hexahydroxy-3,15,27,28-tetramethyl-1-oxacyclooctacosa-17,19,21,23,25-pentaen-2-one |
| Canonical SMILES | CC1C=CC=CC=CC=CC=CC(C(C(CC(CC(CCCC(CC(C(C(=O)OC1C)C)O)O)O)O)O)C)O |
| InChI | InChI=1S/C31H50O8/c1-21-14-11-9-7-5-6-8-10-12-17-28(35)22(2)29(36)20-27(34)18-25(32)15-13-16-26(33)19-30(37)23(3)31(38)39-24(21)4/h5-12,14,17,21-30,32-37H,13,15-16,18-20H2,1-4H3/b6-5+,9-7+,10-8+,14-11+,17-12+ |
| InChI Key | RXFPIRNYTBRDOG-LHKSPRDVSA-N |
Properties
| Appearance | Light Yellow Powder |
| Antibiotic Activity Spectrum | fungi |
| Boiling Point | 784.4°C at 760 mmHg |
| Density | 1.074 g/cm3 |
Reference Reading
1. The Safety and Efficacy of Novel Agents Targeting Factors XI and XII in Early Phase Human Trials
Emma P DeLoughery, Sven R Olson, Cristina Puy, Owen J T McCarty, Joseph J Shatzel Semin Thromb Hemost. 2019 Jul;45(5):502-508. doi: 10.1055/s-0039-1692439. Epub 2019 Jun 19.
Although anticoagulation without hemorrhage is a primary aim, this vision has remained as yet out of reach. Even despite the superior safety profile of the direct oral anticoagulants, hemorrhage remains a major risk of anticoagulation. Selective inhibition of the contact pathway of coagulation, specifically coagulation factor XI (FXI) and/or factor XII (FXII), has now substantial epidemiologic and preclinical data supporting the notion that these factors contribute to pathologic thrombosis and are yet primarily dispensable for in vivo hemostasis. In this way, targeting FXI and FXII may revolutionize the future anticoagulation landscape. Several drugs are under development for this purpose, including: ISIS 416858, a FXI antisense oligonucleotide which impairs hepatic synthesis of FXI; MAA868, a monoclonal antibody that binds the procoagulant enzymatic site of both zymogen and activated FXI (FXIa); BAY 1213790, a monoclonal antibody that binds the procoagulant enzymatic site of FXIa only; and AB023, a monoclonal antibody that inhibits activated FXII-mediated activation of FXI, along with two small molecules in clinical trials. Each of these drugs have demonstrated favorable safety profiles in their phases 1 and 2 studies to date, with preclinical data also supporting efficacy of abrogating thrombosis in various animal models. Other benefits of some of these drugs include once-monthly dosing and safety in patients with renal or hepatic impairment, while others offer quickly metabolized parenteral options, thus providing more convenient and widely available anticoagulation options. Though still far from the marketplace, drugs targeting FXI and FXII have the potential to usher in a new era of anticoagulation therapy.
2. Pharmacological reduction of coagulation factor XI reduces macrophage accumulation and accelerates deep vein thrombosis resolution in a mouse model of venous thrombosis
Kelley R Jordan, Cory R Wyatt, Meghan E Fallon, Randy Woltjer, Edward A Neuwelt, Quifang Cheng, David Gailani, Christina Lorentz, Erik I Tucker, Owen J T McCarty, Monica T Hinds, Khanh P Nguyen J Thromb Haemost. 2022 Sep;20(9):2035-2045. doi: 10.1111/jth.15777. Epub 2022 Jul 18.
Background: Deep vein thrombosis (DVT) and post-thrombotic syndrome (PTS) remain highly prevalent despite modern medical therapy. Contact activation is a promising target for safe antithrombotic anticoagulation. The anti-factor XI (FXI) monoclonal antibody 14E11 reduces circulating levels of FXI without compromising hemostasis. The human recombinant analog, AB023, is in clinical development. The role of FXI in mediation of inflammation during DVT resolution is unknown. Objectives: Investigate the effects of pharmacological targeting of FXI with 14E11 in an experimental model of venous thrombosis. Methods: Adult wild-type CD1 mice were treated with subcutaneous anti-FXI antibody (14E11, 5 mg/kg) versus saline prior to undergoing surgical constriction of the inferior vena cava (IVC). Mice were evaluated at various time points to assess thrombus weight and volume, as well as histology analysis, ferumoxytol enhanced magnetic resonance imaging (Fe-MRI), and whole blood flow cytometry. Results: 14E11-treated mice had reduced thrombus weights and volumes after IVC constriction on day 7 compared to saline-treated mice. 14E11 treatment reduced circulating monocytes by flow cytometry and macrophage content within thrombi as evaluated by histologic staining and Fe-MRI. Collagen deposition was increased at day 3 while CD31 and smooth muscle cell actin expression was increased at day 7 in the thrombi of 14E11-treated mice compared to saline-treated mice. Conclusion: Pharmacologic targeting of FXI enhances the early stages of experimental venous thrombus resolution in wild-type CD1 mice, and may be of interest for future clinical evaluation of the antibody in DVT and PTS.
3. The contact activation inhibitor AB023 in heparin-free hemodialysis: results of a randomized phase 2 clinical trial
Christina U Lorentz, Erik I Tucker, Norah G Verbout, Joseph J Shatzel, Sven R Olson, Brandon D Markway, Michael Wallisch, Martina Ralle, Monica T Hinds, Owen J T McCarty, David Gailani, Jeffrey I Weitz, András Gruber Blood. 2021 Dec 2;138(22):2173-2184. doi: 10.1182/blood.2021011725.
End-stage renal disease (ESRD) patients on chronic hemodialysis have repeated blood exposure to artificial surfaces that can trigger clot formation within the hemodialysis circuit. Dialyzer clotting can lead to anemia despite erythropoietin and iron supplementation. Unfractionated heparin prevents clotting during hemodialysis, but it is not tolerated by all patients. Although heparin-free dialysis is performed, intradialytic blood entrapment can be problematic. To address this issue, we performed a randomized, double-blind, phase 2 study comparing AB023, a unique antibody that binds factor XI (FXI) and blocks its activation by activated FXII, but not by thrombin, to placebo in 24 patients with ESRD undergoing heparin-free hemodialysis. Patients were randomized to receive a single predialysis dose of AB023 (0.25 or 0.5 mg/kg) or placebo in a 2:1 ratio, and safety and preliminary efficacy were compared with placebo and observations made prior to dosing within each treatment arm. AB023 administration was not associated with impaired hemostasis or other drug-related adverse events. Occlusive events requiring hemodialysis circuit exchange were less frequent and levels of thrombin-antithrombin complexes and C-reactive protein were lower after AB023 administration compared with data collected prior to dosing. AB023 also reduced potassium and iron entrapment in the dialyzers, consistent with less blood accumulation within the dialyzers. We conclude that despite the small sample size, inhibition of contact activation-induced coagulation with AB023 was well tolerated and reduced clotting within the dialyzer. This trial was registered at www.clinicaltrials.gov as #NCT03612856.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
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g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
