NPASS Compound

Natural Product: NPC150210

Natural Product ID	NPC150210
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	LHDWRKCOQQHAMP-ZETCQYMHSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	11019159
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000472] Hydroxy acids and derivatives [CHEMONTID:0001713] Beta hydroxy acids and derivatives

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 27 26 0 0 0 0 0 0 0 0999 V2000 -4.0279 0.5824 -0.6768 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5009 -0.7702 -0.3280 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9953 -0.8599 -0.4499 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3222 0.1306 0.4717 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0811 -0.0032 0.3104 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9727 0.7821 1.0324 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4514 1.6067 1.8262 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4485 0.6762 0.8958 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8670 -0.3515 -0.0991 C 0 0 2 0 0 0 0 0 0 0 0 0 4.4015 -0.3418 -0.1248 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4730 -0.0665 -1.4028 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1144 0.4901 -0.9435 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9296 1.2819 0.1983 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5358 1.0420 -1.5446 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9563 -1.5486 -0.9680 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7476 -0.9611 0.7461 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6582 -1.8679 -0.1374 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6549 -0.6701 -1.4684 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5635 1.1847 0.2095 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6447 -0.0980 1.5036 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9053 1.6495 0.5989 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8635 0.4152 1.8706 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4834 -1.3308 0.1845 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7505 0.5052 -0.7405 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7188 -1.3181 -0.5136 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7154 -0.2065 0.9306 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5191 0.0476 -1.5283 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 8 9 1 0 9 10 1 0 9 11 1 0 1 12 1 0 1 13 1 0 1 14 1 0 2 15 1 0 2 16 1 0 3 17 1 0 3 18 1 0 4 19 1 0 4 20 1 0 8 21 1 0 8 22 1 0 9 23 1 1 10 24 1 0 10 25 1 0 10 26 1 0 11 27 1 0 M END

Standard InCHIKey	LHDWRKCOQQHAMP-ZETCQYMHSA-N
Standard InCHI	InChI=1S/C8H16O3/c1-3-4-5-11-8(10)6-7(2)9/h7,9H,3-6H2,1-2H3/t7-/m0/s1
SMILES	CCCCOC(=O)C[C@H](C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	160.11	Volume:	170.659 ? Van der Waals volume.
Dense:	0.938	LogP:	1.254 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.103 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-0.967 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	1.0
TPSA:	46.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	1.0	Rings:	0.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.484	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.485	Fsp³:	0.875
MCE-18:	2.0 ? 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:	0.21	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.009 ? 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:	0.996	Promiscuous compounds:	0.154

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.721	MDCK Permeability:	-4.715
Pgp-inhibitor:	0.001	Pgp-substrate:	0.388
PAMPA:	0.708 ? 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):	0.025
20% Bioavailability (F20%):	0.215	30% Bioavailability (F30%):	0.315
50% Bioavailability (F50%):	0.939

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.424	MRP1:	0.775
Plasma Protein Binding (PPB):	60.432%	Volume Distribution (VD):	0.228
Fu:	39.429% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.505
OATP1B3 inhibitor:	0.928	BCRP inhibitor:	0.192
BSEP inhibitor:	0.734

ADMET: Metabolism

CYP1A2-inhibitor:	0.316	CYP1A2-substrate:	0.992
CYP2C19-inhibitor:	0.122	CYP2C19-substrate:	0.077
CYP2C9-inhibitor:	0.064	CYP2C9-substrate:	0.007
CYP2D6-inhibitor:	0.003	CYP2D6-substrate:	0.017
CYP3A4-inhibitor:	0.436	CYP3A4-substrate:	0.898
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.636
HLM stability:	0.226 ? 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):

8.542

Half-life (T1/2):

0.868

ADMET: Toxicity

hERG Blockers:	0.104	hERG Blockers (10um):	0.45
Human Hepatotoxicity (H-HT):	0.194	Drug-induced Liver Injury (DILI):	0.137
AMES Toxicity:	0.411	Rat Oral Acute Toxicity:	0.362
Maximum Recommended Daily Dose:	0.328	Skin Sensitization:	0.967
Carcinogencity:	0.722	Eye Corrosion:	0.965
Eye Irritation:	0.995	Respiratory Toxicity:	0.574
Drug-induced Neurotoxicity:	0.25	Ototoxicity:	0.106
Hematotoxicity:	0.065	Drug-induced Nephrotoxicity:	0.377
Genotoxicity:	0.006	RPMI-8226 Immunitoxicity:	0.058
A549 Cytotoxicity:	0.158	Hek293 Cytotoxicity:	0.104
BCF:	0.678 ? 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:	2.721 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.081 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.705 ? 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
NPO25933	Elysia rufescens	Species	Placobranchidae	Eukaryota	n.a.	n.a.	n.a.	PMID[15743176]
NPO25933	Elysia rufescens	Species	Placobranchidae	Eukaryota	n.a.	Hawaiian	n.a.	PMID[18407693]
NPO25933	Elysia rufescens	Species	Placobranchidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25777	Acacia longifolia	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26593	Astragalus canadensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26460	Serratia odorifera	Species	Yersiniaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12963	Angelica anomala	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26303	Tacca esquirolii	Species	Taccaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25777	Acacia longifolia	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26593	Astragalus canadensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12963	Angelica anomala	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26735	Stevia amambayensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25933	Elysia rufescens	Species	Placobranchidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26460	Serratia odorifera	Species	Yersiniaceae	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 NPC150210 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	16058
0.1-0.2	30288
0.2-0.3	3322
0.3-0.4	141
0.4-0.5	39
0.5-0.6	8
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	Natural Product ID
0.64	Remote Similarity	NPC166804
0.5714	Remote Similarity	NPC476550
0.56	Remote Similarity	NPC3693
0.56	Remote Similarity	NPC476549
0.5385	Remote Similarity	NPC140229
0.5333	Remote Similarity	NPC603612
0.5172	Remote Similarity	NPC322892
0.5172	Remote Similarity	NPC35371
0.5172	Remote Similarity	NPC12904

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC150210 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5762
0.1-0.2	3168
0.2-0.3	208
0.3-0.4	10
0.4-0.5	1
0.5-0.6	0
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
0.6154	Remote Similarity	NPD900	Pre-clinical

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