| Pharmaceutical Information |
| Drug Name |
Ecallantide |
| Drug ID |
BADD_D00738 |
| Description |
Ecallantide is a potent and selective human plasma kallikrein inhibitor that is indicated for the symptomatic treatment of hereditary angioedema. Ecallantide is a recombinant 60-amino-acid protein produced in _Pichia pastoris_ yeast cells that contains three intramolecular disulfide bonds [FDA Label]. It was discovered by phage display technology [A32017]. It shares sequence similarities with the naturally occurring human protein tissue-factor pathway inhibitor (TFPI), which is also known lipoprotein-associated coagulation inhibitor (LACI) [L1458]. The amino acid sequence of two compounds differ by seven amino acids [L1458].
Ecallantide works by blocking kallikrein to participate in the kallikrein-kinin system, which is a complex proteolytic cascade that initiates inflammatory and coagulation pathways [FDA Label]. The protease plasma kallikerin facilitates the conversion of kininogen to bradykinin, which is a pro-inflammatory vasodilator that increases vascular permeability and induces pain [A3362]. Hereditary angioedema is a rare autosomal dominant disorder with mutations to C1-esterase-inhibitor (C1-INH) located on Chromosome 11q, resulting in substantially lower levels of C4 and C1-INH activity [FDA Label]. The disorder is associated with recurrent attacks of severe swelling and is thought to be caused by unregulated activity of kallikrein and excessive bradykinin production [FDA Label]. By reversibly binding to plasma kallikrein, ecallantide displays a rapid on-rate and a slow off-rate that results in high affinity inhibition in the picomolar range [L1458]. Ecallantide is marketed by FDA and EMA under the trade name Kalbitor for subcutaneous injection. Apart from its FDA and EMA indication, ecallantide has been used off label in the management of nonhistaminergic angioedema, not due to HAE [A32017]. |
| Indications and Usage |
Intravenous administration of ecallantide doses ≥20 mg/m^2 resulted in prolongation of activated partial thromboplastin time (aPTT) without an indication of bleeding. Ecallantide administration has been associated with instances of arrhythmia. In a clinical trial of patients experiencing acute attacks of hereditary angioedema (HAE), intravenous administration of ecallantide demonstrated a significant improvement in symptoms affecting the oropharynx, abdomen, gastrointestinal tract, and limbs within 4 hours post-administration compared to placebo [A32016]. A substantial decrease in the severity and duration of attacks was also observed in patients with moderate-to-severe HAE attacks [A32014]. In clinical trials, ecallantide had no significant effect on the QTc interval, heart rate, or any other components of the ECG [FDA Label]. |
| Marketing Status |
Prescription |
| ATC Code |
B06AC03 |
| DrugBank ID |
DB05311
|
| KEGG ID |
D03931
|
| MeSH ID |
C511194
|
| PubChem ID |
44152182
|
| TTD Drug ID |
D0P5AE
|
| NDC Product Code |
63508-001; 47783-101 |
| Synonyms |
ecallantide | EPI-KAL-2 | DX-88 cpd | DX-88 | DX 88 | kalbitor |
|
| Chemical Information |
| Molecular Formula |
C305H442N88O91S8 |
| CAS Registry Number |
460738-38-9 |
| SMILES |
CCC(C)C1C(=O)NC(C(=O)NCC(=O)NCC(=O)NC2CSSCC3C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O
)N4CCCC4C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(
C(=O)NC(C(=O)NC(CSSCC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(CSSCC(C(=O)NC(C(=O)NC(C(=O
)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NCC(=O)N5CCCC5C(=O)N3)CC(=O)O)CC(=O)O)C)CCCCN)C
C6=CC=CC=C6)C)NC(=O)C(CC7=CC=CC=C7)NC(=O)C(CO)NC(=O)C(CC8=CN=CN8)NC(=O)C(CCSC)NC
(=O)C(C)NC(=O)C(CCC(=O)O)N)C(=O)NC(C(C)O)C(=O)NC(CCCNC(=N)N)C(=O)NC(CC(=O)O)C(=O
)O)CCSC)CCCCN)CCCCN)NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=
O)C(NC(=O)C(NC(=O)C(NC(=O)CNC(=O)C(NC2=O)CCC(=O)O)CC(=O)N)CCC(=O)N)CC(=O)N)CCCNC
(=N)N)CC9=CC=CC=C9)CCC(=O)O)CO)CC(C)C)CCC(=O)O)CCC(=O)O)C(=O)NC(C(=O)NC(C(=O)NC(
C(=O)N1)CC1=CC=CC=C1)CCC(=O)O)CCC(=O)O)CCC(=O)N)CCCNC(=N)N)C(C)O)CC1=CC=CC=C1)C(
C)CC)CC(=O)N)CC1=CC=CC=C1)CC1=CC=CC=C1)CC1=CNC2=CC=CC=C21)CCCNC(=N)N)CC1=CN=CN1)
C)C)CCCNC(=N)N)CC1=CC=C(C=C1)O |
| Chemical Structure |
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|
| ADR Related Proteins Induced by Drug |
| ADR Term |
Protein Name |
UniProt AC |
TTD Target ID |
PMID |
| Not Available | Not Available | Not Available | Not Available | Not Available |
|
| ADRs Induced by Drug |
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