Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C71H110N28O13 |
| Molecular Weight | 1563.8157 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 11 / 11 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
C[C@@H](N)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCNC(N)=N)C(=O)N[C@H](CC1=CN=CN1)C(=O)N[C@H](CC2=CN=CN2)C(=O)NCC(=O)N[C@H](CC3=CC=C(O)C=C3)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCNC(N)=N)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CC4=CC=CC=C4)C(=O)N[C@H](CC5=CN=CN5)C(N)=O
InChI
InChIKey=UIBPZXXSPHGPDS-UXLZJAPBSA-N
InChI=1S/C71H110N28O13/c1-41(75)60(103)91-48(15-5-8-24-72)62(105)94-52(19-12-28-85-71(79)80)66(109)99-57(33-46-36-83-40-89-46)69(112)98-56(32-45-35-82-39-88-45)61(104)86-37-58(101)90-54(30-43-20-22-47(100)23-21-43)67(110)95-49(16-6-9-25-73)63(106)93-51(18-11-27-84-70(77)78)64(107)92-50(17-7-10-26-74)65(108)97-55(29-42-13-3-2-4-14-42)68(111)96-53(59(76)102)31-44-34-81-38-87-44/h2-4,13-14,20-23,34-36,38-41,48-57,100H,5-12,15-19,24-33,37,72-75H2,1H3,(H2,76,102)(H,81,87)(H,82,88)(H,83,89)(H,86,104)(H,90,101)(H,91,103)(H,92,107)(H,93,106)(H,94,105)(H,95,110)(H,96,111)(H,97,108)(H,98,112)(H,99,109)(H4,77,78,84)(H4,79,80,85)/t41-,48-,49-,50-,51-,52-,53-,54-,55-,56-,57-/m1/s1
P-113D is a 12 amino-acid antimicrobial peptide drug derived from histatins, which are compounds found naturally in human saliva. It is being pursued as a potential treatment for cystic fibrosis by Demegen, Inc. P-113D has shown potential as an inhalant in chronic suppressive therapy for CF patients. P-113D has demonstrated a high level of in vitro activity against P. aeruginosa, including drug-resistant patient isolates. Because of its unique mechanism of action, this product will not contribute to drug resistance to classical antibiotics. P-113D also has very potent in vitro activity against a variety of Gram (-) and (+) bacteria including P. aeruginosa, S. aureus, H. influenzae, S. typhimurium, E. coli, S. epidermidis, S. mutans and S. sobrinus. In the case of P. aeruginosa and S. aureus, antibacterial activity has been demonstrated against a variety of CF patient clinical isolates which are resistant to traditional antibiotics. P. aeruginosa isolates that produce thick alginate secretions (mucoid phenotype) are also susceptible to killing by P-113D. For both bacteria and fungi such as Candida albicans, P-113D has been shown to kill cells as opposed to simply inhibiting their growth. It has been demonstrated that P-113D acts by binding to the cell surface and increasing the permeability of both the outer and inner membranes of the cells of Gram (-) bacteria, killing them within seconds. P-113D has been shown to be stable for days in sputum from CF patients and is able to significantly reduce the number of bacteria in sputum from CF patients. P-113D has been shown to work in concert with Pulmozyme®, an approved drug used by ~70% of CF patients, which helps reduce the viscosity of the mucous. In 2002 P-113D received orphan drug status for cystic fibrosis in USA.
Approval Year
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15216473
3 rat models of infection: rats received isotonic sodium chloride solution parenterally (control groups), 1 mg of P-113d/kg of body weight, 1 mg of polymyxin B/kg of body weight, or 20 mg of imipenem/kg of body weight.
Route of Administration:
Parenteral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11709321
In five independent experiments, the addition of P-113D to a mixture of P. aeruginosa cells and liquefied sputum resulted in a several-log reduction in the numbers of CFU per milliliter. The LD90 of P-113D was 20 ug/ml (range, 10 to 40 ug/ml). This compares to an LD90 of 1.25 to 2.5 ug/ml for P-113D against the same organism in the absence of sputum.
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FDA ORPHAN DRUG |
156502
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16158147
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DTXSID90172563
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190673-60-0
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ACTIVE MOIETY