NPASS Compound

Natural Product: NPC191597

Natural Product ID	NPC191597
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	NUXSIDPKKIEIMI-LURJTMIESA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	123800
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

RDKit 3D 30 29 0 0 0 0 0 0 0 0999 V2000 -0.6686 -1.4880 -0.7153 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2762 -1.0432 0.3484 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9745 0.2118 -0.1422 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9125 0.7651 0.7402 N 0 0 0 0 0 0 0 0 0 0 0 0 3.1095 0.0736 1.0028 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9703 0.0699 -0.2005 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0918 -0.5072 -0.2116 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5347 0.7162 -1.3426 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7252 -0.5612 -1.1585 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7655 -0.1785 -0.1933 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3768 0.5010 1.0205 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2682 -0.0082 2.1821 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0777 1.8740 0.9572 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6990 0.7350 -0.9623 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.1261 -2.4934 -0.4576 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0835 -1.7616 -1.6706 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1537 -0.9355 1.3162 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0402 -1.8859 0.4335 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1747 0.9698 -0.3097 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3655 -0.0374 -1.1435 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9587 1.7990 0.7872 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6953 0.6236 1.7911 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9513 -0.9443 1.4103 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9912 0.6141 -2.2315 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2556 -0.9880 -2.0968 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2602 0.3936 -1.6062 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3968 -1.0832 0.0455 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0085 2.4208 1.8038 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6688 0.4507 -0.7964 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5121 1.6976 -0.6123 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 6 8 1 0 1 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 11 13 1 0 10 14 1 0 1 15 1 0 1 16 1 0 2 17 1 0 2 18 1 0 3 19 1 0 3 20 1 0 4 21 1 0 5 22 1 0 5 23 1 0 8 24 1 0 9 25 1 0 9 26 1 0 10 27 1 1 13 28 1 0 14 29 1 0 14 30 1 0 M END

Standard InCHIKey	NUXSIDPKKIEIMI-LURJTMIESA-N
Standard InCHI	InChI=1S/C8H16N2O4/c9-6(8(13)14)3-1-2-4-10-5-7(11)12/h6,10H,1-5,9H2,(H,11,12)(H,13,14)/t6-/m0/s1
SMILES	C(CCNCC(=O)O)C[C@@H](C(=O)O)N

Calculated Properties

Physi-Chem Properties

Molecular Weight:	204.11	Volume:	198.806 ? Van der Waals volume.
Dense:	1.027	LogP:	-2.101 ? 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:	-1.463 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	2.0
TPSA:	112.65 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	5.0	Rings:	0.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.387	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.562	Fsp³:	0.75
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:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.194	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.015 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.073 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.013	Promiscuous compounds:	0.646

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.075	MDCK Permeability:	-4.732
Pgp-inhibitor:	0.0	Pgp-substrate:	0.031
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):	0.356
20% Bioavailability (F20%):	0.023	30% Bioavailability (F30%):	0.182
50% Bioavailability (F50%):	0.124

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.054	MRP1:	0.948
Plasma Protein Binding (PPB):	11.905%	Volume Distribution (VD):	-0.351
Fu:	92.84% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.292
OATP1B3 inhibitor:	0.822	BCRP inhibitor:	0.0
BSEP inhibitor:	0.008

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.006	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.234	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.0
HLM stability:	0.01 ? 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):

3.242

Half-life (T1/2):

1.208

ADMET: Toxicity

hERG Blockers:	0.075	hERG Blockers (10um):	0.188
Human Hepatotoxicity (H-HT):	0.526	Drug-induced Liver Injury (DILI):	0.125
AMES Toxicity:	0.573	Rat Oral Acute Toxicity:	0.54
Maximum Recommended Daily Dose:	0.063	Skin Sensitization:	0.982
Carcinogencity:	0.126	Eye Corrosion:	0.839
Eye Irritation:	0.833	Respiratory Toxicity:	0.874
Drug-induced Neurotoxicity:	0.606	Ototoxicity:	0.125
Hematotoxicity:	0.173	Drug-induced Nephrotoxicity:	0.968
Genotoxicity:	0.215	RPMI-8226 Immunitoxicity:	0.118
A549 Cytotoxicity:	0.012	Hek293 Cytotoxicity:	0.037
BCF:	0.077 ? 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:	2.753 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.959 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.322 ? 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
NPO18987	Lupinus polyphyllus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1598	Leucojum vernum	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1598	Leucojum vernum	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1598	Leucojum vernum	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2950	Artemisia saissanica	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26474	Uvaria hookeri	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1598	Leucojum vernum	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3985	Baccharis leptocephala	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18987	Lupinus polyphyllus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4056	Streptomyces roseoviridis	Species	Streptomycetaceae	Bacteria	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

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 NPC191597 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	43359
0.1-0.2	6022
0.2-0.3	342
0.3-0.4	102
0.4-0.5	23
0.5-0.6	8
0.6-0.7	3
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.6452	Remote Similarity	NPC324825
0.6452	Remote Similarity	NPC112890
0.6452	Remote Similarity	NPC316231
0.5667	Remote Similarity	NPC601942
0.5455	Remote Similarity	NPC276928
0.5455	Remote Similarity	NPC64250
0.5455	Remote Similarity	NPC268927
0.5312	Remote Similarity	NPC167986
0.5312	Remote Similarity	NPC140872
0.5312	Remote Similarity	NPC93081
0.5312	Remote Similarity	NPC291186

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC191597 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7006
0.1-0.2	1918
0.2-0.3	175
0.3-0.4	42
0.4-0.5	4
0.5-0.6	4
0.6-0.7	1
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.6452	Remote Similarity	NPD9044	Phase 4
0.5312	Remote Similarity	NPD8804	Phase 4
0.5312	Remote Similarity	NPD8805	Approved
0.5312	Remote Similarity	NPD8809	Phase 3
0.5312	Remote Similarity	NPD9016	Phase 1

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