NPASS Compound

Natural Product: NPC208560

Natural Product ID	NPC208560
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	AIQMLBKBQCVDEY-UOLFYFMNSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	453575
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000220] Pyrrolizidines

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 28 29 0 0 0 0 0 0 0 0999 V2000 2.2734 -1.0474 -0.5881 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9648 -1.5521 0.0538 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3707 -0.3319 0.4266 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.9625 -0.2671 0.7962 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8116 -1.4526 0.4334 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1229 -1.2722 0.8537 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4629 1.0187 0.1460 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.2159 1.6390 -0.5156 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5202 0.4132 -0.8437 C 0 0 1 0 0 0 0 0 0 0 0 0 1.9945 0.4429 -0.8721 C 0 0 1 0 0 0 0 0 0 0 0 0 2.4553 1.1265 0.2510 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4426 2.4660 0.3823 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9965 1.8914 1.0650 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4141 -1.5106 -1.5667 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1142 -1.1406 0.1020 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1621 -2.2713 0.8430 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3520 -2.0138 -0.7736 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0580 -0.1133 1.8969 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7296 -1.7139 -0.6361 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4124 -2.3193 0.9994 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4295 -1.9540 1.4988 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1878 0.7539 -0.6424 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5674 2.2170 -1.3946 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0386 -0.1276 -1.6677 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4574 0.7687 -1.8005 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4743 0.5367 1.0675 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0426 3.0516 -0.1258 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1200 2.7621 0.6112 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 4 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 8 12 1 0 7 13 1 0 10 1 1 0 9 3 1 0 1 14 1 0 1 15 1 0 2 16 1 0 2 17 1 0 4 18 1 1 5 19 1 0 5 20 1 0 6 21 1 0 7 22 1 6 8 23 1 6 9 24 1 6 10 25 1 6 11 26 1 0 12 27 1 0 13 28 1 0 M END

Standard InCHIKey	AIQMLBKBQCVDEY-UOLFYFMNSA-N
Standard InCHI	InChI=1S/C8H15NO4/c10-3-4-7(12)8(13)6-5(11)1-2-9(4)6/h4-8,10-13H,1-3H2/t4-,5+,6-,7-,8+/m1/s1
SMILES	C1CN2[C@H](CO)[C@H]([C@H]([C@H]2[C@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	189.1	Volume:	175.969 ? Van der Waals volume.
Dense:	1.075	LogP:	-1.562 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-1.067 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	0.138 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	9.0
TPSA:	84.16 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	4.0	Rings:	2.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.367	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.263	Fsp³:	1.0
MCE-18:	34.5 ? 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:	0.085	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.167 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.005 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.047	Promiscuous compounds:	0.113

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.545	MDCK Permeability:	-5.027
Pgp-inhibitor:	0.006	Pgp-substrate:	0.879
PAMPA:	0.963 ? 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):	0.198
20% Bioavailability (F20%):	0.378	30% Bioavailability (F30%):	0.654
50% Bioavailability (F50%):	0.728

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.005	MRP1:	0.241
Plasma Protein Binding (PPB):	23.55%	Volume Distribution (VD):	-0.455
Fu:	77.774% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.668
OATP1B3 inhibitor:	0.47	BCRP inhibitor:	0.037
BSEP inhibitor:	0.142

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.105	CYP2C19-substrate:	0.026
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.007
CYP2D6-inhibitor:	0.007	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.29	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.018
HLM stability:	0.047 ? 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):

4.614

Half-life (T1/2):

3.118

ADMET: Toxicity

hERG Blockers:	0.04	hERG Blockers (10um):	0.221
Human Hepatotoxicity (H-HT):	0.368	Drug-induced Liver Injury (DILI):	0.027
AMES Toxicity:	0.487	Rat Oral Acute Toxicity:	0.072
Maximum Recommended Daily Dose:	0.051	Skin Sensitization:	0.664
Carcinogencity:	0.393	Eye Corrosion:	0.034
Eye Irritation:	0.855	Respiratory Toxicity:	0.095
Drug-induced Neurotoxicity:	0.053	Ototoxicity:	0.804
Hematotoxicity:	0.215	Drug-induced Nephrotoxicity:	0.272
Genotoxicity:	0.032	RPMI-8226 Immunitoxicity:	0.038
A549 Cytotoxicity:	0.02	Hek293 Cytotoxicity:	0.061
BCF:	0.229 ? 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:	1.625 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	2.706 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	1.912 ? 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
NPO23250	Plakortis angulospiculatus	Species	Plakinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[14703354]
NPO23250	Plakortis angulospiculatus	Species	Plakinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[1800643]
NPO23250	Plakortis angulospiculatus	Species	Plakinidae	Eukaryota	n.a.	Brazil	n.a.	PMID[18177008]
NPO23250	Plakortis angulospiculatus	Species	Plakinidae	Eukaryota	n.a.	caribbean	n.a.	PMID[20738102]
NPO23250	Plakortis angulospiculatus	Species	Plakinidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10677	Prunus prostrata	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26218	Prosopis africana	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27030	Commiphora sphaerocarpa	Species	Burseraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10677	Prunus prostrata	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26218	Prosopis africana	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10350	Erythrina speciosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27030	Commiphora sphaerocarpa	Species	Burseraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27103	Satureja vulgaris	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25797	Piper divaricatum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26151	Santolina pectinata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26847	Lecidea quernea	Species	Lecideaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25832	Helichrysum drakensbergense	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17806	Richteria pyrethroides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23250	Plakortis angulospiculatus	Species	Plakinidae	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

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 NPC208560 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	45268
0.1-0.2	4524
0.2-0.3	37
0.3-0.4	13
0.4-0.5	14
0.5-0.6	1
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC294883
1.0	High Similarity	NPC12514
0.5484	Remote Similarity	NPC608364

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC208560 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7888
0.1-0.2	1249
0.2-0.3	6
0.3-0.4	5
0.4-0.5	1
0.5-0.6	1
0.6-0.7	0
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
0.5484	Remote Similarity	NPD9444	Discontinued

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