NPASS Compound

Natural Product: NPC223386

Natural Product ID	NPC223386
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	CLVUFWXGNIFGNC-BNWJMWRWSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2111688
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000195] Piperidines

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 28 0 0 0 0 0 0 0 0999 V2000 3.1824 -1.6201 0.0623 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0444 -1.5618 0.8256 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9561 -0.7365 0.1972 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2268 -0.6947 1.0237 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.3234 -0.0604 0.3824 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0296 -1.0919 -0.5012 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4919 -2.1545 0.2697 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0238 1.1885 -0.3484 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3363 1.2921 -0.9352 C 0 0 2 0 0 0 0 0 0 0 0 0 1.3825 0.7183 0.0178 C 0 0 1 0 0 0 0 0 0 0 0 0 1.2131 1.3393 1.2621 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6348 2.6008 -1.2788 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2811 2.3042 0.4654 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0649 -1.2563 -0.8293 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2939 -1.0895 1.7967 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6073 -2.5552 1.0547 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6949 -1.1853 -0.7812 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4978 -1.6772 1.2607 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0822 0.1856 1.1835 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8861 -0.5958 -1.0047 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3328 -1.4900 -1.2612 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3093 -1.8268 0.7515 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7620 1.2756 -1.1997 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3942 0.6458 -1.8570 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3923 0.8242 -0.3647 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1994 2.3171 1.2038 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0852 2.6099 -2.1473 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2348 2.2943 0.7519 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 1 0 5 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 9 12 1 0 8 13 1 0 10 3 1 0 1 14 1 0 2 15 1 0 2 16 1 0 3 17 1 6 4 18 1 0 5 19 1 1 6 20 1 0 6 21 1 0 7 22 1 0 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	CLVUFWXGNIFGNC-BNWJMWRWSA-N
Standard InCHI	InChI=1S/C7H15NO5/c9-1-3-5(11)7(13)6(12)4(2-10)8-3/h3-13H,1-2H2/t3-,4-,5-,6+,7-/m1/s1
SMILES	OC[C@H]1N[C@H](CO)[C@H]([C@H]([C@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	193.1	Volume:	176.02 ? Van der Waals volume.
Dense:	1.097	LogP:	-2.385 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-1.727 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	0.7 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	6.0
TPSA:	113.18 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	6.0	Rings:	1.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.27	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.115	Fsp³:	1.0
MCE-18:	21.714 ? 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:	0.033	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.038 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.004 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.316	Promiscuous compounds:	0.103

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.311	MDCK Permeability:	-4.831
Pgp-inhibitor:	0.001	Pgp-substrate:	0.547
PAMPA:	0.998 ? 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):	0.14
20% Bioavailability (F20%):	0.242	30% Bioavailability (F30%):	0.436
50% Bioavailability (F50%):	0.921

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.152
Plasma Protein Binding (PPB):	24.01%	Volume Distribution (VD):	-0.492
Fu:	84.343% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.169
OATP1B3 inhibitor:	0.099	BCRP inhibitor:	0.014
BSEP inhibitor:	0.039

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.017	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.894
HLM stability:	0.011 ? 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):

2.662

Half-life (T1/2):

2.254

ADMET: Toxicity

hERG Blockers:	0.018	hERG Blockers (10um):	0.206
Human Hepatotoxicity (H-HT):	0.29	Drug-induced Liver Injury (DILI):	0.006
AMES Toxicity:	0.333	Rat Oral Acute Toxicity:	0.02
Maximum Recommended Daily Dose:	0.003	Skin Sensitization:	0.406
Carcinogencity:	0.082	Eye Corrosion:	0.017
Eye Irritation:	0.714	Respiratory Toxicity:	0.003
Drug-induced Neurotoxicity:	0.003	Ototoxicity:	0.956
Hematotoxicity:	0.246	Drug-induced Nephrotoxicity:	0.4
Genotoxicity:	0.001	RPMI-8226 Immunitoxicity:	0.03
A549 Cytotoxicity:	0.004	Hek293 Cytotoxicity:	0.014
BCF:	0.165 ? 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:	1.354 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	2.34 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	1.735 ? 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
NPO33446	aglaonema treubii	Species	Araceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10560746]
NPO25280	Suregada glomerulata	Species	Euphorbiaceae	Eukaryota	Roots	n.a.	n.a.	PMID[18205316]
NPO25280	Suregada glomerulata	Species	Euphorbiaceae	Eukaryota	leaves	n.a.	n.a.	PMID[23993676]
NPO33446	aglaonema treubii	Species	Araceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9544568]
NPO25280	Suregada glomerulata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25280	Suregada glomerulata	Species	Euphorbiaceae	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

Activity Type	# Activity
IC50	5
Inhibition	1
FC	1

Activity Type	# Activity
Individual protein	6
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1055	Individual protein	Neutral alpha-glucosidase C	Mus musculus	IC50	<	50000.0	nM	PMID[11754601]
NPT509	Individual protein	Beta-galactosidase	Bos taurus	IC50	=	160000.0	nM	PMID[11754601]
NPT501	Individual protein	Alpha-galactosidase A	Homo sapiens	FC	=	2.0	n.a.	PMID[23363020]
NPT6631	Individual protein	Neutral alpha-glucosidase C	Homo sapiens	IC50	=	80000.0	nM	PMID[11754601]
NPT6372	Individual protein	Alpha-galactosidase A	Rattus norvegicus	IC50	=	67000.0	nM	PMID[11754601]
NPT503	Individual protein	Alpha-L-fucosidase I	Homo sapiens	Inhibition	>	50.0	%	PMID[9644063]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified	n.a.	IC50	=	24950.0	nM	PMID[20521839]

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 NPC223386 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	46804
0.1-0.2	2888
0.2-0.3	121
0.3-0.4	12
0.4-0.5	10
0.5-0.6	5
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	5

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC75435
1.0	High Similarity	NPC142290
1.0	High Similarity	NPC198341
1.0	High Similarity	NPC471892
1.0	High Similarity	NPC471780
0.7273	Intermediate Similarity	NPC286851
0.7273	Intermediate Similarity	NPC303798
0.7222	Intermediate Similarity	NPC62507
0.7222	Intermediate Similarity	NPC602743
0.6667	Remote Similarity	NPC268922
0.5714	Remote Similarity	NPC474014
0.5714	Remote Similarity	NPC30126
0.5714	Remote Similarity	NPC57846
0.5217	Remote Similarity	NPC474928
0.5161	Remote Similarity	NPC471418

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC223386 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	8511
0.1-0.2	591
0.2-0.3	43
0.3-0.4	1
0.4-0.5	2
0.5-0.6	0
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
		NPD

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