Natural Product (NP) Details

General Information of the NP (ID: NP8393)
Name
Alpha-1 antitrypsin
Species Origin Homo sapiens ...     Click to Show/Hide
Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Disease Coagulation defect [ICD-11: 3B10] Phase 2 [1]
ADMET Property
Absporption
Caco-2 Permeability
 -6.411
 
MDCK Permeability
 -5.54
 
PAMPA
 +++
 
HIA
 +++
 
Distribution
VDss
 -0.628
 
PPB
 17.5%
 
BBB
 - - -
 
Metabolism
CYP1A2 inhibitor
 - - -
CYP1A2 substrate
 - - -
CYP2C19 inhibitor
 - - -
CYP2C19 substrate
 - - -
CYP2C9 inhibitor
 - - -
CYP2C9 substrate
 - - -
CYP2D6 inhibitor
 - - -
CYP2D6 substrate
 - - -
CYP3A4 inhibitor
 - - -
CYP3A4 substrate
 - - -
CYP2B6 inhibitor
 - - -
CYP2B6 substrate
 - - -
CYP2C8 inhibitor
 - - -
HLM Stability
 - - -
 
Excretion
CLplasma
 0.83
 
T1/2
 2.486
Toxicity
DILI
 - - -
 
Rat Oral Acute Toxicity
 - - -
 
FDAMDD
 - - -
 
Respiratory
 - - -
 
Human Hepatotoxicity
 ++
 
Ototoxicity
 +++
 
Drug-induced Nephrotoxicity
 +++
 
Drug-induced Neurotoxicity
 - - -
 
Hematotoxicity
 -
 
Genotoxicity
 - - -
 
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++). 2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
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TTD Drug ID
D04TEF
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Anti-CD4 (GK1.5) antibody      Melanoma     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Islet Xenotransplantation: Rat islets (400/transplant) were implanted under the renal capsule of recipient mice that were rendered hyperglycemic by single-dose streptozotocin.
                    Experimental
                    Result(s)		 Pancreatic islet xenograft survival in mice is extended by a combination of alpha-1-antitrypsin and single-dose anti-CD4/CD8 therapy.
          Doxycycline      Periodontal disease     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model At the age of 10 weeks, DBA/1 mice were immunized intradermally at the base of the tail with 0.1 ml of emulsion containing 100 ug of type II collagen.
                    Experimental
                    Result(s)		 Doxycycline and hAAT in combination also inhibited IL-6 expression from LPS-stimulated NIH/3T3 mouse fibroblast cells, indicating a contributing mechanism of arthritis inhibition.
          Anti-CD8 (53.6.72) antibody      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Islet Xenotransplantation: Rat islets (400/transplant) were implanted under the renal capsule of recipient mice that were rendered hyperglycemic by single-dose streptozotocin.
                    Experimental
                    Result(s)		 Pancreatic islet xenograft survival in mice is extended by a combination of alpha-1-antitrypsin and single-dose anti-CD4/CD8 therapy.
Target and Pathway
Target(s) Trypsin-1 (PRSS1)  Molecule Info  [4]
KEGG Pathway Neuroactive ligand-receptor interaction Click to Show/Hide
2 Pancreatic secretion
3 Protein digestion and absorption
4 Influenza A
Reactome Activation of Matrix Metalloproteinases Click to Show/Hide
2 Cobalamin (Cbl, vitamin B12) transport and metabolism
WikiPathways Activation of Matrix Metalloproteinases Click to Show/Hide
References
Reference 1 Technology evaluation: transgenic alpha-1-antitrypsin (AAT), PPL therapeutics. Curr Opin Mol Ther. 2000 Apr;2(2):199-204.
Reference 2 Pancreatic islet xenograft survival in mice is extended by a combination of alpha-1-antitrypsin and single-dose anti-CD4/CD8 therapy. PLoS One. 2013 May 22;8(5):e63625.
Reference 3 Combination of alpha-1 antitrypsin and doxycycline suppresses collagen-induced arthritis. J Gene Med. 2010 Jan;12(1):35-44.
Reference 4 US patent application no. 2012,0251,516, PHARMACEUTICAL COMPOSITION FOR TREATING CANCER COMPRISING TRYPSINOGEN AND/OR CHYMOTRYPSINOGEN AND AN ACTIVE AGENT SELECTED FROM A SELENIUM COMPOUND, A VANILLOID COMPOUND AND A CYTOPLASMIC GLYCOLYSIS REDUCTION AGENT.
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