Natural Product: NPC140823

Natural Product IDNPC140823
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 YMRZLZUJZNHRLO-DMTCNVIQSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11804803
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000264] Organic acids and derivatives
      • [CHEMONTID:0000265] Carboxylic acids and derivatives
        • [CHEMONTID:0000013] Amino acids, peptides, and analogues
          • [CHEMONTID:0000347] Amino acids and derivatives
            • [CHEMONTID:0000060] Alpha amino acids and derivatives
              • [CHEMONTID:0002404] Alpha amino acids
                • [CHEMONTID:0004146] L-alpha-amino acids

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey YMRZLZUJZNHRLO-DMTCNVIQSA-N
Standard InCHI InChI=1S/C5H11NO3/c1-3(2-7)4(6)5(8)9/h3-4,7H,2,6H2,1H3,(H,8,9)/t3-,4+/m1/s1
SMILES C[C@H](CO)[C@@H](C(=O)O)N

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   133.07 Volume:   129.767
?
Van der Waals volume.
Dense:   1.025 LogP:   -1.827
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.412
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.202
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   1.0
TPSA:   83.55
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   4.0 Rings:   0.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.462 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.206 Fsp3:   0.8
MCE-18:   3.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.108 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.025
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.764 Promiscuous compounds:   0.808

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.77 MDCK Permeability:   -4.187
Pgp-inhibitor:   0.0 Pgp-substrate:   0.072
PAMPA:   0.996
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.003
20% Bioavailability (F20%):   0.002 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.026

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.168 MRP1:   0.76
Plasma Protein Binding (PPB):   19.746% Volume Distribution (VD):   -0.412
Fu: 79.66%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.815
OATP1B3 inhibitor:   0.976 BCRP inhibitor:   0.002
BSEP inhibitor:   0.01

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.004 CYP2C19-substrate:   0.004
CYP2C9-inhibitor:   0.055 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.129 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.007
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.055
HLM stability:   0.0
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  3.844 Half-life (T1/2):  1.985

ADMET: Toxicity

hERG Blockers:  0.019 hERG Blockers (10um):  0.055
Human Hepatotoxicity (H-HT):  0.409 Drug-induced Liver Injury (DILI):  0.077
AMES Toxicity:  0.556 Rat Oral Acute Toxicity:  0.249
Maximum Recommended Daily Dose:  0.044 Skin Sensitization:  0.874
Carcinogencity:  0.378 Eye Corrosion:  0.538
Eye Irritation:  0.927 Respiratory Toxicity:  0.379
Drug-induced Neurotoxicity:  0.25 Ototoxicity:  0.428
Hematotoxicity:  0.39 Drug-induced Nephrotoxicity:  0.468
Genotoxicity:  0.274 RPMI-8226 Immunitoxicity:  0.037
A549 Cytotoxicity:  0.018 Hek293 Cytotoxicity:  0.023
BCF:   0.241
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   2.335
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.687
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.899
?
96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO737 Aspergillus japonicus Species Aspergillaceae Eukaryota n.a. latex n.a. PMID[21854017]
NPO9461 Gmelina leichhardtii Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO395 Teucrium pilosum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11673 Koelreuteria paniculata Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11228 Fritillaria pallidiflora Species Liliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8403 Annona coriacea Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7322 Plagiochila acanthophylla Species Plagiochilaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10101 Rothmannia macrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO737 Aspergillus japonicus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12045 Schottera nicaeensis Species Phyllophoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3670 Crotalaria podocarpa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7322 Plagiochila acanthophylla Species Plagiochilaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11228 Fritillaria pallidiflora Species Liliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12761 Rheum hotaoense Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11673 Koelreuteria paniculata Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9015 Solanum arundo Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15212.1 Fraxinus chinensis subsp. rhynchophylla Subspecies Oleaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11228 Fritillaria pallidiflora Species Liliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3313 Crotalaria trichotoma Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12761 Rheum hotaoense Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO395 Teucrium pilosum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11673 Koelreuteria paniculata Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11673 Koelreuteria paniculata Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11228 Fritillaria pallidiflora Species Liliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11228 Fritillaria pallidiflora Species Liliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15212.1 Fraxinus chinensis subsp. rhynchophylla Subspecies Oleaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO12045 Schottera nicaeensis Species Phyllophoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5310 Eucalyptus bakeri Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11673 Koelreuteria paniculata Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7322 Plagiochila acanthophylla Species Plagiochilaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11228 Fritillaria pallidiflora Species Liliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4919 Kalanchoe daigremontiana Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11540 Acacia leptostachya Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3313 Crotalaria trichotoma Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13095 Pachycereus tehuantepecanus Species Cactaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10101 Rothmannia macrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12761 Rheum hotaoense Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9887 Protohermes grandis Species Corydalidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9461 Gmelina leichhardtii Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4454 Maytenus salicifolia Species Celastraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15212.1 Fraxinus chinensis subsp. rhynchophylla Subspecies Oleaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3670 Crotalaria podocarpa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17461 Hedera canariensis Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO737 Aspergillus japonicus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO395 Teucrium pilosum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9015 Solanum arundo Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8403 Annona coriacea Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC140823 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.6667 Remote Similarity NPC190385
0.6667 Remote Similarity NPC132307
0.6667 Remote Similarity NPC126925
0.6364 Remote Similarity NPC226265
0.6364 Remote Similarity NPC219143
0.6364 Remote Similarity NPC254482
0.6364 Remote Similarity NPC110533
0.6087 Remote Similarity NPC270805
0.6087 Remote Similarity NPC317691
0.6087 Remote Similarity NPC93888
0.6 Remote Similarity NPC116709
0.6 Remote Similarity NPC21290
0.6 Remote Similarity NPC272614
0.5833 Remote Similarity NPC84636
0.5833 Remote Similarity NPC226027
0.5833 Remote Similarity NPC174246
0.5833 Remote Similarity NPC43204
0.56 Remote Similarity NPC49952
0.56 Remote Similarity NPC136476
0.5217 Remote Similarity NPC63621
0.5217 Remote Similarity NPC326992
0.5217 Remote Similarity NPC121517
0.5217 Remote Similarity NPC168375
0.5217 Remote Similarity NPC600066
0.52 Remote Similarity NPC245027
0.52 Remote Similarity NPC43169
0.52 Remote Similarity NPC162620
0.52 Remote Similarity NPC327895
0.52 Remote Similarity NPC62045
0.52 Remote Similarity NPC316685
0.52 Remote Similarity NPC112224

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC140823 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
0.6667 Remote Similarity NPD8798 Phase 2
0.6667 Remote Similarity NPD9023 Clinical (unspecified phase)
0.6364 Remote Similarity NPD8215 Phase 4
0.6364 Remote Similarity NPD8216 Phase 3
0.6364 Remote Similarity NPD8217 Phase 3
0.6087 Remote Similarity NPD8214 Approved
0.6087 Remote Similarity NPD8624 Phase 2
0.6087 Remote Similarity NPD8801 Phase 4
0.6 Remote Similarity NPD8210 Phase 3
0.6 Remote Similarity NPD8211 Approved
0.5833 Remote Similarity NPD9017 Phase 2
0.52 Remote Similarity NPD9018 Phase 3
0.5185 Remote Similarity NPD9021 Pre-clinical

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data